( PDF ) Avaliação do perfil cognitivo dos pacientes com transtorno obsessivo-compulsivo pós-traumático

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INSTITUTO DE PSIQUIATRIA-IPUB

Centro de Ciências da Saúde - CCS

Universidade Federal do Rio de Janeiro

TÍTULO: Avaliação do perfil cognitivo dos pacientes com Transtorno Obsessivo-

Compulsivo pós- traumático.

MANUELA CORRÊA BORGES

Dissertação de Mestrado submetida ao Corpo Docente do Programa de Pós-

Graduação em Psiquiatria e Saúde Mental - PROPSAM do Instituto de Psiquiatria da

Universidade Federal do Rio de Janeiro, como parte dos requisitos necessários para a

obtenção do Grau de Mestre em Saúde Mental.

Orientador: Leonardo Franklin da Costa Fontenelle

Pós-doutorado no Departamento de Anatomia do Instituto de Ciências Biomédicas da

Universidade Federal do Rio de Janeiro. Professor Adjunto do Departamento de

Psiquiatria e Medicina Legal da Universidade Federal do Rio de Janeiro e do Instituto

de Saúde da Comunidade da Universidade Federal Fluminense.

RIO DE JANEIRO

JULHO 2009

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INSTITUTO DE PSIQUIATRIA-IPUB

Centro de Ciências da Saúde - CCS

Universidade Federal do Rio de Janeiro

Avaliação do perfil cognitivo dos pacientes com transtorno obsessivo-

compulsivo pós-traumático.

MANUELA CORRÊA BORGES

Dissertação de Mestrado submetida ao Corpo Docente do Programa de Pós-

Graduação em Psiquiatria e Saúde Mental - PROPSAM do Instituto de Psiquiatria da

Universidade Federal do Rio de Janeiro, como parte dos requisitos necessários para a

obtenção do Grau de Mestre em Saúde Mental.

Aprovada por:

__________________________________

Leonardo Franklin da Costa Fontenelle - Presidente

Doutor em Psiquiatria, Psicanálise e Saúde Mental, Professor Adjunto do

Departamento de Psiquiatria e Medicina Legal da Universidade Federal do Rio de

Janeiro e do Instituto de Saúde da Comunidade da Universidade Federal Fluminense.

_______________________

Mauro Vítor Mendlowicz

Doutor em Psiquiatria, Psicanálise e Saúde Mental, Professor Adjunto do

Departamento de Psiquiatria e Saúde Mental da Universidade Federal Fluminense

___________________________

Paulo Eduardo Luiz de Mattos

Doutor em Psiquiatria, Psicanálise e Saúde Mental. Professor adjunto do

Departamento de Psiquiatria e Medicina Legal da Universidade Federal do Rio de

Janeiro.

Rio de Janeiro

JULHO 2009

ads:

Borges, Manuela Corrêa.

(Avaliação do perfil cognitivo dos pacientes com Transtorno Obsessivo-

Compulsivo pós- traumático /

Manuela Corrêa Borges. Rio de Janeiro:

UFRJ/Instituto de Psiquiatria, 2009.)

(CCXXXIII), (232)p.

Bibliografia: p.(118-124)

Orientador (a): Leonardo Franklin da Costa Fontenelle

Dissertação Mestrado Universidade Federal do R

io de Janeiro,

IPUB.

1. (Neuropsicologia) 2. (Transtorno Obsessivo-

Compulsivo) 3.

(Transtorno de Estresse Pós-

Traumático) I. Avaliação do perfil

cognitivo dos pacientes com Transtorno Obsessivo-

Compulsivo e

Transtorno de Estresse Pós-Traumático comórbi

dos. II.

Dissertação Mestrado.

DEDICATÓRIA

Dedico este trabalho aos meus pais, irmã e marido, pessoas que jamais duvidaram de

minha capacidade e sempre estiveram ao meu lado para a conclusão desta pesquisa.

Além disso, dedico-o aos pacientes avaliados que, gentilmente, se disponibilizaram a

participar desta pesquisa apenas pelo retorno científico que ela poderia gerar.

AGRADECIMENTOS

Agradeço a Deus, por iluminar cada dia da minha vida.

Agradeço a meus pais e minha irmã, por fazerem parte da minha vida de forma

permanente, intensa e exemplar. Muito obrigada pelas palavras de incentivo, amor e

por confiarem sempre em mim.

Agradeço a meu marido, Caio, por todo amor que cresce cada dia que passa... Muito

obrigada por todos os dias em que ficou ao meu lado enquanto eu trabalhava na

idealização e consolidação desta pesquisa.

Agradeço ao meu orientador Leonardo Fontenelle pela intensa dedicação e pela

gentileza de compartilhar seus conhecimentos comigo.

Agradeço ao meu amigo Gabriel Coutinho, por sempre se disponibilizar a me ajudar e

por me ceder horas de seus dias para me dar conselhos, fazer correções e me dizer

palavras de incentivo.

Agradeço a Catia Araújo, Ângela Alfano e Paulo Mattos por me mostrarem a riqueza

da neuropsicologia e o quanto podemos colaborar para o progresso da ciência e para a

melhora dos pacientes.

Agradeço a todos do C-TOC, que direta ou indiretamente colaboraram para a

concretização desta pesquisa.

O CTOC é subsidiado pelo Conselho Nacional de Desenvolvimento Científico e

Tecnológico (CNPq, i.e. Projeto Milennium) e por fundos da Fundação de Amparo à

Pesquisa do Estado de São Paulo (Fapesp).

RESUMO

Este trabalho pretende descrever os déficits neuropsicológicos de pacientes que

desenvolveram Transtorno Obsessivo-Compulsivo (TOC) após a ocorrência de um

evento traumático (i.e. TOC pós-traumático). Há relatos na literatura científica de que

pacientes com TOC associado ao transtorno do estresse pós-traumático (TEPT)

apresentam, tanto do ponto de vista clínico quanto de resposta ao tratamento, um

perfil diferente dos pacientes que apresentam apenas TOC ou apenas TEPT. No

entanto, não temos conhecimento de estudos prévios que tenham avaliado, do ponto

de vista neuropsicológico, pacientes com “TOC pós-traumático”. A investigação deste

subgrupo de pacientes com TOC tem o intuito de esclarecer se estes pacientes formam

um grupo específico do espectro do TOC, se seriam mais semelhantes ao grupo de

pacientes com TEPT ou se teriam um perfil cognitivo específico. Este esforço visa o

aprimoramento das técnicas de tratamento e a melhora da qualidade de vida dos

pacientes com TOC pós-traumático. No presente estudo, (1) descrevemos, em uma

revisão narrativa, os principais déficits cognitivos presentes em pacientes com TOC e

(2) comparamos o perfil neuropsicológico de pacientes com TOC pós-traumático

(TOC após TEPT) ao de pacientes com TOC pré-traumático (TEPT após o TOC),

TOC não-traumático (TOC sem TEPT) e controles normais. A avaliação

neuropsicológica consistiu em testes que investigaram a capacidade cognitiva global,

as funções executivas e as habilidades mnêmicas. Para a avaliação da capacidade

cognitiva global foi utilizado o WASI (Wechsler Abbreviated Scale of Intelligence),

composto pelo teste de vocabulário, semelhanças, matrizes e cubos. A avalição de

memória foi composta pelo subteste de Memória Lógica (da bateria Wechsler de

Memória-WMS), para a avaliação da memória auditivo-verbal e, pelo Brief

Visuomotor Memory Test – Revised (BVMT-R), para a avaliação da memória não-

verbal. As funções executivas foram avaliadas pelo Wisconsin Card Sorting Test

(WCST) e pelo Iowa Gambling Test (IGT), que endereçam funções dos circuitos

frontais dorso-lateral e orbito-medial, respectivamente. Os resultados obtidos sugerem

que os pacientes do grupo “TOC pós-traumático” apresentaram resultados piores,

comparados aos pacientes dos três demais grupos (TOC “não-traumático”, TOC “pré-

traumático” e controles), nos testes de capacidade cognitiva global (QI), memória

verbal e não-verbal e de funções executivas.

ABSTRACT

This study intends to describe the neuropsychological deficits of patients who

developed Obsessive-Compulsive Disorder (OCD), after the occurrence of a trauma

(“Post-Traumatic OCD”). There are in scientific literature some studies that suggest

that patients with OCD who developed Post-Traumatic Stress Disorder (PTSD)

presents different profiles relating to clinical characteristics and treatment responses,

compared to patients with “only” OCD or “only” Post-Traumatic Stress Disorder

(PTSD). However there is no evidence of previous studies that had been analyzed, on

the neuropsychological point of view, the patients with “Post-Traumatic OCD”. The

objective of this investigation is to determine if this OCD subgroup (Post-Traumatic

OCD) is more similar to the OCD spectrum or to the PTSD group or if it would be

another group with its own neuropsychological characteristics. This study has the

objective to help in the upgrade of treatment techniques and promote quality of life. In

the present study, (1) we will describe, in a narrative revision way, the

neuropsychological profile of “pure” OCD patients and (2) we will compare the

neuropsychological profile of four groups, “Post-Traumatic OCD” (OCD after

PTSD), “Pre-Traumatic OCD” (PTSD after OCD), “Non-Traumatic OCD” (OCD

without PTSD) and healthy control group. The Neuropsychological assessment was

composed by global cognitive test (IQ), memory and executive functions tests. In

order to investigate the global cognitive capacity we used the WASI (Wechsler

Abbreviated Scale of Intelligence), composed by vocabulary, similarities, matrix and

block design subtests. The memory battery was composed by Logical Memory (from

Wechsler Memory Scale – WMS), for verbal memory assessment and, by Brief

Visuomotor Memory Test – Revised (BVMT-R), for nonverbal memory. The

executive functions were evaluated by Wisconsin Card Sorting Test (WCST) and by

Iowa Gambling Test (IGT), for assessment of dorsolateral and orbitomedial prefrontal

circuits, respectively. The results suggest that Post-Traumatic OCD had worse

performance, compared to control, non-trauma OCD and Pre-traumatic OCD groups,

on all tests applied of global cognitive (IQ), verbal and nonverbal memory and

executive function tests.

1) INTRODUÇÃO

1.1) Transtorno Obsessivo-Compulsivo

O Transtorno Obsessivo-Compulsivo (TOC) é definido pela presença de

obsessões e/ou compulsões com reconhecimento, por parte do portador, em algum

momento da doença, que os pensamentos ou os comportamentos são excessivos e

irracionais (Diagnostic and Statistical Manual-IV; APA, 1994).

As obsessões são idéias, pensamentos, impulsos ou imagens persistentes, que

são vivenciados como intrusivos e inadequados e causam acentuada ansiedade ou

sofrimento. A qualidade intrusiva e inadequada das obsessões é chamada de "ego-

distônica".

O termo refere-se ao sentimento do indivíduo de que o conteúdo da obsessão é

estranho, não está dentro de seu próprio controle nem é a espécie de pensamento que

ele esperaria ter. Entretanto, ele é capaz de reconhecer que as obsessões são produto

de sua própria mente e não impostas a partir do exterior (como na inserção de

pensamento).

As obsessões mais comuns são pensamentos repetidos acerca de

contaminação, dúvidas repetidas, uma necessidade de organizar as coisas em

determinada ordem, impulsos agressivos ou horrorizantes e imagens sexuais.

As compulsões são comportamentos repetitivos ou atos mentais cujo objetivo

é prevenir ou reduzir a ansiedade ou sofrimento, ao invés de oferecer prazer ou

gratificação.

Na maioria dos casos, a pessoa sente-se compelida a executar a compulsão

para reduzir o sofrimento que acompanha uma obsessão ou para evitar algum evento

ou situação temidos.

O Transtorno Obsessivo-Compulsivo pode estar associado com Transtorno

Depressivo Maior, outros Transtornos de Ansiedade (Fobia Específica, Fobia Social,

Transtorno de Pânico, Transtorno de Estresse Pós-Traumático), Transtornos

Alimentares e Transtorno da Personalidade Obsessivo-Compulsiva e Transtorno de

Tourette.

Embora o Transtorno Obsessivo-Compulsivo anteriormente fosse considerado

relativamente raro na população geral, atualmente estima-se uma prevalência durante

a vida de 2,5% e uma prevalência anual de 1,5-2,1%.

Recentemente, o TOC tem sido associado, ao menos em parte, a déficits

neuropsicológicos assim como os demais Transtornos de Ansiedade (Greisberg e

McKay, 2003).

O TOC apesar de ser considerado uma entidade neuropsiquiátrica homogênea

e específica, se apresenta com uma considerável variabilidade clínica e, por isso, tem

sido estudado como um transtorno heterogêneo no que se refere às suas principais

características (Lochner e Stein, 2003).

Pesquisadores e clínicos têm observado que algumas vezes, pacientes com

tipos específicos de sintomas são menos responsivos aos tratamentos hoje oferecidos,

assim, métodos para identificar subtipos do TOC e avaliar possíveis diferenças na

resposta ao tratamento ou na etiologia do transtorno têm sido bastante valorizados

(McKay et al., 2004).

Pelo fato de a heterogeneidade deste transtorno trazer implicações clínicas e de

pesquisas relevantes, Lochner e Stein (2003) admitem que algumas subdivisões do

TOC são válidas e oferecem ferramentas úteis que permitem integrar dados da

sintomatologia, da neurobiologia e da resposta ao tratamento.

Nesse sentido, estes autores propuseram alguns subtipos do transtorno e,

dentre estes, podem ser citados:

• a idade de início dos sintomas (Sobin et al., 2000; Rosario-Campos et

al., 2001; Fontenelle et al., 2003);

• as diferentes classes de sintomas (Fontenelle et al., 2004);

• as diferenças de gênero (Castle, et al., 1995; Lensi, et al 1996;

Bogetto et al. 1999; Fontenelle et al., 2002);

• e o nível de insight dos portadores de TOC (Kishore et al (2004),

Türksoy et al (2002)).

O crescente interesse na identificação de subtipos do TOC é verificado, pois

esta ferramenta pode facilitar a comunicação dentro da rede de profissionais de saúde,

desenvolver bases para teorias de psicopatologia, predizer o curso clínico e identificar

que tratamentos são mais prováveis de serem efetivos para cada paciente (McKay et

al, 2004).

A neuropsicologia do TOC também vem sendo estudada com o intuito de

fornecer ferramentas aos clínicos e pesquisadores para melhor compreenderem este

transtorno.

Os estudos relativos a este tema já identificaram regiões e/ou circuitos

cerebrais afetados e funções cognitivas preservadas, nesse transtorno; já forneceram

informações para a construção de modelos patofisiológicos do TOC e para sua

distinção em relação a outras patologias do sistema nervoso central; e, já

identificaram circuitos neurais envolvidos nos sintomas do TOC e suas possíveis

influências nos diferentes tratamentos deste transtorno (Fontenelle et al, 2006).

1.1.1) DISFUNÇÕES NEUROPSICOLÓGICAS DO TOC

Estudos de neuropsicologia do TOC vêm sendo caracterizados por achados

inconsistentes, que se relacionam à heterogeneidade do transtorno. Uma divisão

confiável dos subtipos do TOC é importante, pois hipóteses de que os subtipos estão

associados a perfis neurocognitivos distintos traz implicações para os modelos de

etiologia do transtorno e para seu manejo clínico.

Os perfis neuropsicológicos têm sido considerados como possíveis métodos

válidos para subdividir o TOC, já que poderão servir ainda como fonte de dados

preditivos para escolha de tratamentos, avaliação de severidade, curso e comorbidades

do TOC, entre outras vulnerabilidades do transtorno. De maneira geral, pesquisas têm

demonstrado que disfunções fronto-estriatais estão presentes no TOC (McKay et al,

2004).

O sistema orbitofrontal modula os conteúdos emocionais das informações

recebidas, bem como o controle inibitório e a sensibilidade às contingências de

reforçamento. Além disso, esse sistema desempenha um grande papel no

funcionamento da memória, mantendo ainda conexão importante com o setor

temporal medial (Aycicegi et al 2003).

Pesquisas trazem evidências de que o córtex dorsolateral-prefrontal também

está implicado nas disfunções do TOC (Harris e Dinn, 2003). Tal circuito media as

funções executivas e muitos estudos verificam comprometimento destas funções em

pacientes com TOC, entretanto, os achados ainda são inconclusivos (Purcell et al,

1998; Lucey et al, 1997).

Fontenelle et al (2006)

endossam a teoria de comprometimento dos circuitos

dorsolateral prefrontal e orbitomedial prefrontal, nos pacientes com TOC. Estudos de

lesão e neuroimagem que ajudam a descobrir as disfunções neuropsicológicas dos

pacientes com TOC, sugerem que o comprometimento do funcionamento do córtex

dorsolateral prefrontal está mais relacionado ao baixo desempenho em tarefas

direcionadas à descoberta de regras e à memória operacional, enquanto que a

performance em testes relacionados à inibição de resposta e ao controle atencional é

mais dependente da integridade do funcionamento do córtex orbitomedial prefrontal.

Desta forma, estudos que investigam a hipótese de existência de disfunções no

córtex prefrontal dorsolateral (CPFDL), em pacientes com TOC, encontram déficits:

• na troca de cenário cognitivo,

• na fluência verbal,

• na memória operacional

• e no planejamento.

Já as pesquisas que avaliam a hipótese de disfunções no córtex prefrontal

orbitomedial (CPFOM), verificam:

• uma baixa capacidade de alternância a curto prazo,

• um comprometimento na tomada de decisões,

• déficits de atenção seletiva,

• execução comprometida de testes que exigem ações e pensamentos

espontâneos,

• lentidão na execução e adoção de estratégias organizacionais

improdutivas,

• baixa performance em tarefas Go/No-go,

• presença de respostas confabulatórias

• e identificação olfatória comprometida (Fontenelle et al, 2006).

Disfunções mnêmicas também se verificam em pacientes com TOC. Há uma

hipótese de que o comprometimento das memórias verbal e não-verbal esteja

relacionado às disfunções executivas, envolvendo planejamento e organização. Além

disso, um componente motor, incluindo a coordenação de movimentos complexos

também pode estar envolvido no comprometimento mnêmico (Fontenelle et al, 2006).

Os circuitos de memória explícita e implícita também se revelam

comprometidos, no TOC, assim como a memória incidental, a meta-memória, a

memória para ações, o viés mnêmico, a monitoração de realidade e a ordenação

temporal (Jurado et al, 2001; Jurado et al, 2002; McNally et al, 1993; MacDonald et

al, 1997; Tuna et al, 2005; Constans et al, 1995; Hermans et al, 2003; van den Hout

et al, 2003; Ecker eEngelkamp, 1995; Merckelbach e Wessel, 2000; Radomsky e

Rachman, 1999; Radomsky et al, 2001; Tolin et al, 2002; Ceschi et al, 2003;

Wilhelm et al, 1996; Reed, 1977; Rubenstein et al, 1993; Brown et al, 1994).

Além disso, os resultados de um estudo recente realizado por Cuttler et al

(2007), para avaliar a memória prospectiva sugerem que os déficits nas memórias

prospectiva e retrospectiva trabalham em conjunto na produção e manutenção da

tendência da checagem compulsiva. Assim, déficits de memória prospectiva também

já foram verificados nestes pacientes.

O comprometimento de habilidades viso-espaciais e viso-construtivas é um

dos achados mais consistentemente reportados nos estudos de disfunções

neuropsicológicas do TOC (Mataix-cols., 2001; Kim et al., 2002; Christensen et al.,

1992; Boone et al., 1991; Savage et al., 1999 ).

Entretanto alguns resultados sugerem que tais déficits podem refletir a

existência de disfunção executiva primária (função do córtex dorsolateral prefrontal) -

Mataix-Cols, 2001.

Apesar de se reconhecer que o funcionamento sensorial e motor também são

importantes aspectos do TOC que deveriam fazer parte das baterias

neuropsicológicas, poucos estudos nesta área têm sido feitos (Greisberg et al, 2003).

Entretanto, a influência de comorbidades e o uso de medicações também não

foram desvinculadas aos déficits de forma inequívoca.

1.2) Transtorno de Estresse Pós-Traumático

A característica essencial do Transtorno de Estresse Pós-Traumático (TEPT) é

o desenvolvimento de sintomas característicos após a exposição a um extremo

estressor traumático, envolvendo a experiência pessoal direta de um evento real ou

ameaçador que envolve morte, sério ferimento ou outra ameaça à própria integridade

física; ter testemunhado um evento que envolve morte, ferimentos ou ameaça à

integridade física de outra pessoa; ou o conhecimento sobre morte violenta ou

inesperada, ferimento sério ou ameaça de morte ou ferimento experimentados por um

membro da família ou outra pessoa em estreita associação com o indivíduo.

A resposta ao evento deve envolver intenso medo, impotência ou horror (em

crianças, a resposta pode envolver comportamento desorganizado ou agitado). Os

sintomas característicos resultantes da exposição a um trauma extremo incluem uma

revivência persistente do evento traumático, esquiva persistente de estímulos

associados com o trauma, embotamento da responsividade geral e sintomas

persistentes de excitação aumentada.

Os indivíduos com TEPT podem descrever sentimentos de culpa por terem

sobrevivido quando outros morreram ou pelas coisas que tiveram de fazer para

sobreviverem. A esquiva fóbica de situações ou atividades que lembram ou

simbolizam o trauma original pode interferir nos relacionamentos interpessoais e

acarretar conflito conjugal, divórcio ou perda do emprego. A seguinte constelação de

sintomas associados pode ocorrer, sendo vista com maior freqüência em associação

com um estressor interpessoal (por ex., abuso físico ou sexual na infância, tortura):

prejuízo na modulação do afeto; comportamento auto-destrutivo e impulsivo;

sintomas dissociativos; queixas somáticas; sensações de inutilidade, vergonha,

desespero ou desamparo; sensação de dano permanente; perda de crenças

anteriormente mantidas; hostilidade; retraimento social; sensação de constante

ameaça; prejuízo no relacionamento com outros; ou uma mudança nas características

anteriores de personalidade do indivíduo.

Pode haver um risco aumentado de Transtorno de Pânico, Agorafobia,

Transtorno Obsessivo-Compulsivo, Fobia Social, Fobia Específica, Transtorno

Depressivo Maior, Transtorno de Somatização e Transtornos Relacionados a

Substâncias. Não se sabe até que ponto esses transtornos precedem ou se seguem ao

início do Transtorno de Estresse Pós-Traumático. Estudos comunitários revelam uma

prevalência durante a vida do TEPT variando de 1 a 14%, estando a variabilidade

relacionada aos métodos de determinação e à população estudada. Estudos de

indivíduos de risco (por ex., veteranos de guerra, vítimas de erupções vulcânicas ou

violência criminal) sugerem taxas de prevalência variando de 3 a 58%.

1.2.1) DISFUNÇÕES NEUROPSICOLÓGICAS DO TEPT

Muitos estudos têm apontado para déficits neuropsicológicos associados a

traumas e ao Transtornos de Estresse Pós-Traumático (Yehuda et al. 2006; Jelinek et

al, 2006; Sailer et al, 2008). De maneira geral, estudos de neuropsicologia envolvendo

pacientes com TEPT sugerem déficits nas funções atentivas, mnêmicas e executivas.

O TEPT tem sido visto como um transtorno caracterizado pela incapacidade

de processar e integrar as informações relacionadas ao trauma, sendo descrito como

um transtorno do processamento da informação. Uma diminuição do controle

inibitório e das funções executivas relacionadas às memórias traumáticas, às emoções

e aos impulsos pode descrever este transtorno (Johnsen, e Asbjφrnsen, 2009).

Há evidências de que o TEPT está associado a padrões de disfunção cerebral e

déficits cognitivos específicos (Elzinga e Bremner, 2002). Alterações no aprendizado

verbal e na memória têm sido consistentemente documentados (Bremner et al, 2004;

Gilberston et al, 2001). Além disso, aspectos da atenção e da memória dependentes do

controle executivo aparecem comprometidos nestes pacientes (Kanagaratnam e

Asbjornsen, 2007; Vasterling et al., 1998).

Estudos recentes correlacionam o TEPT e o comprometimento de memória

verbal, tanto no que se refere à aquisição (Yehuda et al., 2005) quanto ao resgate de

material, levando a uma diminuição da habilidade de consolidação deste material

(Bremner et al, 1995; Uddo et al., 1993). Estes achados sugerem um padrão de

déficits mnêmicos associado a dificuldades no uso de estratégias organizacionais e de

aprendizado eficazes durante a aquisição do material (Sternberg e Tulving, 1977).

Por outro lado, Jenkins et al. (1998) verificaram que, apesar de sua amostra de

TEPT não parecer comprometida na aquisição ao longo das tentativas de aprendizado

verbal, ela se mostrou comprometida nos resgates imediato e tardio. Estudos também

indicaram que a capacidade cognitiva global tem sido vista como um fator de risco

para o desenvolvimento de TEPT (Macklin et al., 1998), sendo importante controlar o

QI em estudos neuropsicológicos.

Em uma revisão dos estudos do funcionamento cognitivo no TEPT, Horner e

Hamner (2002) apontam para uma gama de estudos que sugerem diminuição do

hipocampo, nos pacientes com TEPT, comparados, tanto a grupos-controle como a

grupos de pacientes expostos a traumas, mas sem diagnóstico de TEPT. De fato, o

grau de redução do volume hipocampal parece variar de 5 a 26% (Stein et al, 1997;

Gurvits et al, 1996), podendo ocorrer à direita, à esquerda ou bilateralmente.

Diminuição do hipocampo à direita ou bilateralmente relacionava-se a pacientes que

desenvolveram TEPT mais tardiamente, enquanto diminuição do volume à esquerda

estava associada à ocorrência de traumas precoces na vida (Bremner, 1999 em

Caminha, 2005).

Em um estudo de Bremner et al (1997b), apesar de ter sido verificada redução

do hipocampo em adultos que sofreram abuso na infância (cerca de 12% comparados

a controles pareados), não foi verificada correlaçãodo volume hipocampal esquerdo

ou direito e o desempenho no teste de memória verbal aplicado. Estudos de

neuroimagem funcional também identificaram regiões com alterações do fluxo

sanguíneo em pacientes com TEPT. Foi observado, com certa reprodutibilidade,

redução na ativação do hemisfério esquerdo. As estruturas encontradas com

hipoperfusão sanguínea foram o córtex pré-frontal médio/ cíngulo anterior e córtex

pré-frontal dorsolateral, o hipocampo e a área de Broca. Já as áreas com ativação mais

elevada foram o giro para-hipocampal e do cíngulo posterior, além da amígdala em

paradigmas específicos de provocação de sintomas (Bremner, 2002 em Caminha,

2005).

No estudo de Weniger et al (2008), maiores volumes do hipocampo e da

amígdala foram associados a melhores desempenhos nas tarefas cognitivas (de

atenção e memória) em adultos que sofreram abuso na infância e desenvolveram

transtornos dissociativos. Alguns autores sugerem que a gravidade dos sintomas do

TEPT influencia negativamente no desempenho de tarefas que avaliam as funções

cognitivas, assim, a maior gravidade dos sintomas está associada a maiores déficits

mnêmicos (Bremmer et al, 1993). Além disso, Wild et al (2008) verificaram que o

grau de dificuldade mnêmica diferenciava os pacientes que obtiveram melhora com o

tratamento daqueles que não melhoraram (quanto maior o déficit mnêmico, menor a

melhora no tratamento).

O comprometimento de memória verbal parece estar relacionado tanto à

aquisição quanto ao controle executivo. Assim, o comprometimento de memória pode

estar associado a estratégias deficitárias na aquisição de material e não limitado à

capacidade mnêmica em si (Wild et al, 2008). Os déficits de memória verbal foram

verificados mesmo controlando-se a influência de comorbidades, dificuldades

atentivas e capacidade cognitiva global (Wild, J et al, 2008). Por outro lado, Dickie et

al (2005) verificaram que os pacientes com TEPT apresentavam déficits mnêmicos,

parcialmente explicados por disfunções atentivas e de memória operacional. Na

revisão de Horner e Hamner (2002), déficits atentivos, tanto visuais como auditivos,

foram verificados nos pacientes com TEPT.

1.3) A INFLUÊNCIA DOS EVENTOS TRAUMÁTICOS NO

TRANSTORNO OBSESSIVO-COMPULSIVO

A ligação entre o TOC e trauma foi reconhecida há mais de três décadas atrás

quando Janet e Raymond (1976) sugeriram que, muitos casos de TOC avaliados por

eles, haviam sido causados por traumas emocionais. Num estudo em 1980,

Hollingsworth et al., verificaram a presença de acontecimentos considerados

“ameaçadores” em 15 das 17 crianças avaliadas antes do início dos sintomas

obsessivo-compulsivos, levando-os a hipotetizar que tais sintomas seriam uma forma

de defesa primitiva contra as memórias ameaçadoras intrusivas.

Mais tarde, Khana et al (1988) encontraram na história da doença de sua

amostra de pacientes com TOC, um significativo número de eventos traumáticos

ocorridos seis meses antes do aparecimento dos sintomas obsessivo-compulsivos. De

forma semelhante, Toro et al (1992) observaram que a ocorrência de eventos

traumáticos havia precedido o início dos sintomas obsessivo-compulsivos de 53% de

seus pacientes diagnosticados com TOC.

Um estudo epidemiológico na população geral apontou o risco aumentado em

10 vezes de pacientes com TEPT desenvolverem TOC, enquanto um estudo

vietnamita encontrou prevalência de TOC em torno de 5,2% em zonas consideradas

de “alto estresse”, mas apenas de 0,3% em zonas de guerra consideradas de “baixo ou

moderado estresse” (Jordan et al., 1991). Possíveis explicações para esta relação já

foram levantadas, dentre elas as explicações de modelo cognitivo e biológico.

O modelo cognitivo explicaria esta relação a partir dos efeitos cognitivos

negativos trazidos pelo trauma, o que geraria um aumento da ansiedade e uma

consequente rotulação negativa dos estímulos como extremamente ameaçadores. Esta

forma de pensar levaria a mecanismos compensatórios, como os rituais compulsivos,

com o objetivo de diminuir a excitação emocional (Riggs, 2000; Dinn et al, 1999).

O modelo biológico, por sua vez, enfatiza o papel do sistema serotoninérgico

no desenvolvimento de ambos os transtornos (DeSilva e Marks, 2001; Dinn et al,

1999). Estes autores sugerem que o estresse crônico leva a um aumento da atividade

serotoninérgica e hipermetabolismo orbitofrontal, que envolve uma alteração da

responsividade celular. A vulnerabilidade sentida, o aumento da ansiedade e a

rotulação dos estímulos como ameaçadores durante o trauma levam os pacientes a se

engajarem em compulsões na tentativa de diminuição do estresse devido à excessiva

atividade neuronal nesta região.

Alguns relatos de caso sugeriram que o trauma tem um papel etiológico no

TOC e que existe uma relação entre TOC e TEPT tanto em termos sintomáticos

quanto diagnósticos (DeSilva et al 1999; Pitman, 1993). Até 2008, não havia

estudos indicando a prevalência de trauma ou TEPT nos pacientes com TOC.

Gershuny et al (2008) avaliaram, então, a prevalência desta patologia em pacientes

que buscavam tratamento para TOC refratário. Os autores encontraram uma alta

prevalência em sua amostra (40%), assemelhando-se aos resultados obtidos em um

estudo conduzido por Mueser et al (1998) avaliando uma amostra caracterizada por

sujeitos com graves doenças mentais (43%). Entretanto, a prevalência encontrada, em

ambos estudos, foi bem mais alta que em estudos comunitários (9%, em Breslau et al,

1991) e em população psiquiátrica geral (28%, em McFarlane et al, 2001).

1.3.1) CLÍNICA

Ambos os transtornos parecem se relacionar tanto em termos de cronicidade

quanto em termos de aparecimento agudo dos sintomas (Sasson et al, 2005). Apesar

de alguns autores sugerirem que as imagens e pensamentos intrusivos do TOC se

assemelham aos flashbacks do TEPT, Sasson et al (2005) preferem identificar os

sintomas obsessivo-compulsivos como uma forma distinta de sintomatologia nos

pacientes com TEPT, ou seja, os pensamentos intrusivos relacionados ao trauma

constituem um padrão típico de sintomas obsessivos. Tais sintomas causam intenso

mal-estar e comportamentos repetitivos são realizados com o objetivo de minimizar

ou eliminar os pensamentos indesejáveis. No caso destes pacientes, a sintomatologia

obsessivo-compulsiva relaciona-se à temática do trauma.

Cromer et al (2007) investigaram o impacto de eventos traumáticos na

gravidade dos sintomas obsessivo-compulsivos e verificaram que os pacientes que

haviam desenvolvido TOC após o trauma apresentavam uma expressão clínica do

TOC mais grave, de acordo com escores da YBOCS (Goodman et al, 1989). Estes

autores verificaram que as obsessões e compulsões relacionadas ao grupo de sintomas

de checagem e simetria/ordenação eram mais freqüentes neste grupo de pacientes.

Foi encontrada uma relação interessante na forma de expressão dos sintomas

da comorbidade nos pacientes “TOC pós-traumáticos”, segundo a série de casos

descrita por Gershuny et al (2003): quando os sintomas do TOC diminuíam de

frequência e intensidade, os sintomas do TEPT aumentavam consideravelmente;

quando os sintomas obsessivo-compulsivos aumentavam, os sintomas traumáticos,

diminuíam, sugerindo uma “conexão dinâmica” entre ambos os transtornos na sua

forma de expressão.

1.3.2) HISTÓRIA FAMILIAR

Não foi verificada a existência de história familiar de TOC em nenhum dos

casos citados no estudo de Gershuny et al (2003), que realizou uma descrição de uma

série de casos de “TOC pós-traumático”. Apenas em um deles, houve relato de

comportamentos obsessivo-compulsivos no filho do paciente estudado.

1.3.3) NEUROIMAGEM

Em uma meta-análise, Rotge et al (2009) identificaram a existência de um

menor volume cerebral das regiões do córtex do cíngulo anterior e do córtex órbito-

frontal, assim como um aumento do volume do tálamo, em pacientes com TOC. A

porção afetiva do córtex do cíngulo anterior, e suas conexões ao sistema límbico,

estão implicadas na avaliação emocional da informação e na regulação da resposta

emocional, possivelmente mediando a expressão da ansiedade observada no TOC. Já

a porção cognitiva está envolvida na detecção de erros e monitoração de estímulos

conflitivos.

O córtex órbito-frontal relaciona-se com a representação de valores de

informações novas e com o controle inibitório dos comportamentos. Alterações nesta

região podem estar relacionadas à superestimação dos riscos e à diminuição do

controle dos comportamentos perseverativos no TOC. O volume do tálamo está

diretamente ligado à gravidade do TOC. Ele é uma importante estrutura que transmite

e processa informações neuronais dos gânglios basais às áreas corticais. Os resultados

desta meta-análise (Rotge et al., 2009) sugerem que as alterações funcionais do córtex

do cíngulo anterior e da atividade do córtex órbito-frontal estão associadas a

anormalidades estruturais.

Os achados mais consistentes da neuroimagem no TEPT vieram dos estudos

estruturais com ressonância magnética, que demonstraram, em sua maioria, lesões

inespecíficas de substância branca e redução do volume hipocampal em populações

heterogêneas de adultos com TEPT (Villarreal et al, 2002 em Caminha, 2005). Já os

estudos de neuroimagem funcional apontaram para um padrão de resposta exacerbado

da amígdala, a partir de estudos de provocação de sintomas nos pacientes com TEPT.

Outros estudos apontaram para uma diminuição na atividade de regiões do córtex pré-

frontal medial, incluindo o córtex do cíngulo anterior e córtex órbito-frontal nos

pacientes com TEPT (Dickie et al, 2008).

Os autores acima citados sugerem que os indivíduos com TEPT possuem uma

disfunção no circuito fronto-temporal, sugerindo a existência de um substrato neural

anormal mediando a função mnêmica, tanto para estímulos traumáticos quanto para

neutros. Por outro lado, um punhado de estudos de neuroimagem funcional

identificou alguma sobreposição dos sintomas obsessivo-compulsivos e traumáticos.

Rauch et al (1997) avaliaram 23 pacientes que preenchiam critérios para TOC, TEPT

ou fobia específica e verificaram que, durante a provocação de sintomas, o fluxo

sanguíneo aumentava em regiões do circuito paralímbico, juntamente com regiões do

córtex frontal inferior direito e núcleo subcortical. Já Lucey et al (1997) verificaram

que tanto os pacientes com TOC quanto os com TEPT diferiram de pacientes com

Transtorno do Pânico e controles saudáveis no que se refere ao fluxo sanguíneo no

córtex frontal superior bilateral e no núcleo caudado direito (Fontenelle et al 2007).

Entretanto, até a última pesquisa nas bases eletrônicas de dados investigadas, não foi

encontrado nenhum estudo de neuroimagem (funcional ou estrtutural) que avaliasse o

efeito da comorbidade (TEPT-TOC) no funcionamento cerebral ou nas regiões /

circuitos cerebrais envolvidos.

1.3.4) TRATAMENTO PSICOTERÁPICO E MEDICAMENTOSO

Com o objetivo de avaliar o impacto do trauma no tratamento dos pacientes

com TOC, Gershuny et al., (2002) conduziram um estudo de tratamento naturalístico

não-cego. Estes autores verificaram que os pacientes que não preenchiam critérios

para TEPT tiveram melhor resposta ao tratamento (terapia comportamental intensiva)

e diminuição da severidade da depressão quando comparados aos pacientes com TOC

e TEPT co-mórbidos.

O impacto negativo do trauma nos resultados da terapia puderam ser

vistos através da melhora inicial dos sintomas do TOC mas piora intensa dos

flashbacks, pesadelos e lembranças traumáticas, além de uma posterior piora dos

sintomas obsessivo-compulsivos tanto em intensidade quanto em freqüência. Devido

à “conexão dinâmica” na expressão da comorbidade TOC-TEPT, Gershuny et al

(2003) sugerem que, atuando terapeuticamente em cada patologia isoladamente, a

eficácia do tratamento ficará comprometida. Os autores sugerem que os sintomas

obsessivo-compulsivos podem ter uma função “evitativa” contra os pensamentos e

lembranças traumáticas: quando os primeiros diminuem, os outros aumentam e vice-

versa. Portanto, sugerem que ambos os transtornos sejam tratados durante o processo

psicoterápico de forma sistemática.

No que tange aos medicamentos, os tratamentos de primeira linha para os

transtornos ansiosos são os Inibidores Seletivos de Recaptação de Serotonina (ISRS).

Anti-depressivos tricíclicos também podem ser usados de forma eficaz em alguns

casos (Bendelow, B. et al, 2008). No entanto, não há uma diretriz de tratamento

medicamentoso quando a comorbidade TOC-TEPT se faz presente.

Graber et al (2008) sugerem que possivelmente os pacientes que

possuem a comorbidade TEPT-TOC procurem menos os serviços de tratamento

especializados em programas de TOC, preferindo tratar-se em ambulatórios de TEPT

devido à maior predominância destes sintomas. Gershuny et al (2003) questionam

como os pacientes que possuem a comorbidade “TOC pós-traumático” devem ser

pensados: se como pacientes apresentando dois diagnósticos separados ou como

sendo um subtipo específico e complexo de TEPT. Estudos visando esclarecer como a

sobreposição destes sintomas se expressa e evolui são necessários, tanto do ponto de

vista neuropsicológico, como de intervenção (seja para tratamento medicamentoso ou

psicoterápico).

1.3.5) NEUROPSICOLOGIA

Não foram encontrados estudos, nas bases de dados investigadas até a última

pesquisa, que avaliassem o perfil cognitivo dos pacientes que desenvolveram TOC

após a exposição a traumas (e desenvolvimento de TEPT). Com o intuito de avaliar as

funções cognitivas deste grupo de pacientes chamados “TOC pós-traumático”, o

presente estudo foi conduzido. Foram avaliadas a capacidade cognitiva global, as

funções executivas e a capacidade mnêmica. A descrição dos déficits

neuropsicológicos comumente presentes em ambas patologias, separadamente, foi

anteriormente relatada e serviu como base para a escolha dos testes utilizados no

presente estudo.

2) Apresentação da Produção Científica

2.1) Capítulo de Livro (Editora Revinter)

ASPECTOS NEUROCOGNITIVOS DOS

TRANSTORNOS DO ESPECTRO OBSESSIVO-COMPULSIVO

Manuela C. Borges

, Leonardo F. Fontenelle

RUNNING HEAD: NEUROPSICOLOGIA DO TOC

Programa de Ansiedade e Depressão do Instituto de Psiquiatria da

Universidade Federal do Rio de Janeiro (IPUB/UFRJ)

Endereço: Dr. Leonardo F. Fontenelle, Rua Visconde de Pirajá 547, Sala

719, Ipanema, Rio de Janeiro, CEP: 22410-900. Tel: ++55-21-22394919.

Agradecimentos: Este trabalho foi apoiado por uma bolsa do CNPq

(Processo n

141517/00-0).

INTRODUÇÃO

A neuropsicologia tem colaborado com o avanço no entendimento do

transtorno obsessivo-compulsivo (TOC) em diversos aspectos (Fontenelle et al.,

2006). Em primeiro lugar, tem permitido identificar as diversas áreas de

comprometimento e de preservação das funções cognitivas de pacientes com TOC.

Em segundo lugar, a neuropsicologia tem proporcionado, juntamente com estudos de

neuroimagem e de processamento de informações, a elaboração de modelos

fisiopatológicos do TOC cada vez mais aprimorados (Otto, 1992; Cottraux e Gerard,

1998; Savage, 1998). Em terceiro lugar, a neuropsicologia tem emergido como uma

área de potencial relevância para o manejo terapêutico do TOC. Finalmente, a

neuropsicologia tem contribuído para uma redefinição dos limites diagnósticos do

TOC, com identificação de subtipos e com o estabelecimento de conexões com

transtornos psiquiátricos outrora considerados independentes do TOC (os chamados

transtornos do espectro obsessivo-compulsivo).

Neste trabalho, realizamos uma revisão dos principais achados

neuropsicológicos em pacientes com TOC, suas potenciais implicações para o

tratamento, e como eles podem contribuir para uma redefinição dos limites do TOC.

FUNÇÕES EXECUTIVAS

Entendemos por funções executivas as funções mentais superiores que

modulam as habilidades mais elementares como, por exemplo, as funções senso-

perceptivas, as motoras e as atentivo-mnésicas. O funcionamento executivo,

estreitamente ligado à integridade dos lobos frontais e às suas conexões, implica na

capacidade de ter em conta todos os elementos de uma dada situação para então

antecipar as situações, selecionar os objetivos, planejar as respostas, reavaliar e iniciar

as respostas planejadas, monitorar as respostas em execução e avaliar suas

conseqüências de modo a modificar o comportamento (Benson, 1994; Mataix-cols,

2001).

Um número impressionante de diferentes disfunções executivas tem sido

identificado em pacientes com TOC. Como os testes neuropsicológicos possuem uma

função localizadora limitada e insatisfatória (i.e. estes instrumentos identificam

“sistemas”, e não regiões, disfuncionais), qualquer tentativa de atribuir uma disfunção

cognitiva a uma única região ou a uma estrutura cerebral deve ser considerada com

cautela. Com essas considerações em mente, e na tentativa de sintetizar a grande

heterogeneidade dos achados sobre a neuropsicologia do TOC, procuramos, a seguir,

relacionar alguns destes resultados a disfunções de dois sistemas funcionais, o circuito

pré-frontal dorso-lateral (CPFDL) e o circuito pré-frontal órbito-medial (CPFOM)

(Fuster, 1989). Curiosamente, a grande maioria dos estudos parece sugerir que

pacientes com TOC apresentam disfunções de um ou de outro sistema.

Estudos de lesão e neuroimagem que ajudam a investigar as disfunções

neuropsicológicas dos pacientes com TOC, sugerem que o comprometimento do

funcionamento do CPFDL está mais relacionado ao baixo desempenho em tarefas

direcionadas à descoberta de regras, à memória operante, à troca de cenário cognitivo,

à fluência verbal e ao planejamento, enquanto que a performance em testes

relacionados à inibição de resposta e ao controle atentivo é mais dependente da

integridade do funcionamento do CPFOM.

Dentre os estudos nos quais foram encontrados achados supostamente

compatíveis com uma disfunção do CPFDL encontram-se aqueles que identificaram

(1) comprometimento na mudança do cenário cognitivo, avaliada com instrumentos

como o Wisconsin Card Sorting Test (WCST) (Harvey et al., 1986; Malloy et al.,

1997; Head et al., 1989; Hymas et al., 1991; Christensen et al., 1992; Lucey et al.,

1997; Okasha et al; 2000; Fontenelle et al., 2001; Lacerda et al., 2003), o Trail

Making Test (Hollander et al., 1991; Hollander et al., 1996; Aronowitz et al., 1994;

Fontenelle et al., 2001; Kim et al., 2002; Kim et al., 2003), e a Attentional Set-Shifting

Task do Cambridge Neuropsychological Test Automated Battery (Veale et al., 1996);

(2) comprometimento da fluência verbal, estudada com o Controlled Oral Word

Asssociation Test (COWAT) (Harvey et al., 1986; Head et al., 1989; Hymas et al.,

1991; Kim et al., 2002); (3) comprometimento da memória operante, avaliada com o

Self Ordering Pointing Task (Martin et al., 1995; Galderisi et al., 1995) com o Spatial

Working Memory (Purcell et al., 1998 a,b) e (4) comprometimento do planejamento,

de acordo com os achados na Tower of Hanoi (Cavedini et al., 2001; Fernandez et al.,

2003) na Tower of London (Veale et al., 1996; Purcell et al., 1998 a,b).

Em outros estudos, foram observados padrões de disfunção cognitiva

compatíveis com a existência de uma disfunção do CPFOM. Estes padrões incluíram

(1) preservação do desempenho no WCST associada ao declínio da capacidade de

alternância a curto prazo, avaliada com o Objects Alternation Test ou testes

semelhantes (Abbruzzese et al., 1995; Abbruzzese et al., 1997; Cavedini et al., 1998;

Gross-Isseroff et al., 1996; Moritz et al., 2001); (2) comprometimento da capacidade

de tomada de decisões, de acordo com o desempenho no Gambling Task (Cavedini et

al., 2002); (3) disfunção da atenção seletiva, demonstrada pelo desempenho

comprometido no Stroop Test

(Harston et al., 1999; Bannon et al., 2002) e em suas

versões “emocionais” (Foa et al., 1993; Lavy et al., 1994; Kyrios and Iob, 1998;

Unoki et al., 1999), em uma tarefa de primming negativo (Enright and Beech, 1993) e

no Test of Everyday Attention (Clayton et al., 1999); (4) comprometimento da

execução de testes que avaliam pensamentos e ações rápidas e espontâneas, como o

Weight Sorting Task e o Digit Connection (Schmidtke et al., 1998) ; (5) lentidão na

execução (Roth et al., 2004) e adoção de estratégias organizacionais improdutivas no

Rey-Osterrieth Complex Figure Test (RCFT) (Behar et al., 1984; Savage et al., 1999;

Savage et al., 2000) e em uma tarefa de registro de material linguístico complexo

(Cabrera et al., 2001); (6) comprometimento do desempenho do teste go-non-go

(Aycicegi et al., 2003); (7) presença de respostas confabulatórias, identificadas

através do California Verbal Learning Test (CVLT) (Zielinski et al., 1991); e,

finalmente, (8) comprometimento da capacidade de identificação olfatória, avaliada

com o University of Pennsylvania Smell Identification Test (Barnett et al., 1999).

Quais circuitos estariam realmente disfuncionais em pacientes com TOC? Esta

pergunta está longe de ser respondida. Alguns estudos chegaram a identificar, por

exemplo, sindromes disexecutivas compatíveis com disfunções nos circuitos pré-

frontais dorso-lateral e órbito-medial simultaneamente (Cavedini et al., comunicação

pessoal). Recentemente, Penadés et al (2007) observaram que o desempenho de

pacientes com TOC foi significativamente inferior ao de controles saudáveis na

inibição seletiva de comportamentos motores (reações mais lentas), avaliada pelo

Go/No-Go, e na inibição da interferência cognitiva no teste do Stroop e motora no

teste Stop. A inibição da resposta motora esperada nos testes Stop e no Go/No-go se

relaciona à ativação das regiões média e inferior de lobo frontal e dos gânglios basais,

Martinot et al. (1990) observaram em pacientes com TOC uma correlação negativa entre o

metabolismo no CPFDL e tanto o número de erros quanto o tempo mensurado na situação de

interferência do Stroop test.

enquanto que a inibição cognitiva (Stroop) tem sido associada à ativação das regiões

cerebrais pré-frontais dorsolateral e mesial, sugerindo possíveis disfunções destas

regiões nos pacientes com TOC. Além disso, tanto os estudos neuropsicológicos que

identificaram alterações cognitivas sugestivas de disfunção em um circuito quanto os

que as identificaram no outro possuem suas limitações.

Estudos que encontraram desempenho comprometido no WCST, por exemplo,

têm sido criticados por incluir pacientes com menor inteligência ou sintomas

depressivos clinicamente significativos na ausência de um grupo controle adequado

(Mataix-cols., 2001; Kuelz et al., 2004). Corroborando pelo menos uma destas

hipóteses em alguns estudos, os pacientes com TOC com maior gravidade dos

sintomas depressivos caracterizaram-se por pior desempenho em testes executivos

[como o WCST, o Trail Making Test (Basso et al., 2001; Moritz et al., 2001; Mataix-

cols. et al., 2003) e o Verbal Concept Attainment Test (Basso et al., 2001)] e não-

executivos (Moritz et al., 2003; Mataix-cols. et al., 2003). No estudo de Aycicegui et

al. (2003), uma análise de covariância demonstrou que o comprometimento do

desempenho da parte B do Trail Making Test e do COWAT em pacientes com TOC

eram resultantes da presença concomitante de sintomas depressivos e esquizotípicos.

No estudo de Harris e Dinn (2003), quando comparados ao grupo controle, os

pacientes com TOC demonstraram déficits significativos em tarefas mediadas pelo

CPFOM, referentes a controle inibitório (Object Alternation Task, Stroop, e tarefa

Go/No-go). Entretanto, em tarefas dependentes do circuito do CPFDL, relacionadas às

funções executivas (fluência verbal, tarefa de pensamento divergente), os déficits

encontrados nos pacientes com TOC também foram associados à presença de traços

esquizotípicos.

Seguindo esta linha, em um estudo de Shin et al (2008), os pacientes com

TOC que apresentavam traços de personalidade esquizotípica mostraram pior

desempenho no WCST (categorias concluídas) e em dois tipos de tarefa de fluência

verbal sensíveis a disfunções do CPFDL e CPFOM, quando comparados aos controles

saudáveis, enquanto que os pacientes com TOC sem traços esquizotípicos não

apresentaram déficits nos mesmos testes. Desta forma, os autores concluíram que

traços esquizotípicos quando concomitantes ao TOC podem ser responsáveis por

déficits mais amplos das funções pré-frontais.

A atribuição de um desempenho insatisfatório no WCST a sintomas

comórbidos em pacientes com TOC também foi observada em indivíduos com

sintomas obsessivo-compulsivos subclínicos. Por exemplo, no estudo de Goodwin et

al (1992), que comparou checadores compulsivos a não-checadores quanto ao

desempenho no WCST, os autores sugeriram que o elevado número de erros e ao

maior tempo demandado para a realização da tarefa no primeiro grupo estavam

relacionados ao alto nível de ansiedade intrínseca presente no primeiro grupo.

Por outro lado, em uma grande parte dos estudos que encontraram

preservação do desempenho no WCST, foram incluídos pacientes com TOC

medicados (Abbruzzese et al., 1995; Abbruzzese et al., 1997; Zielinski et al., 1991).

Abbruzzese et al. (1995), por exemplo, notaram que o desempenho no WCST de

pacientes com TOC em uso de doses elevadas de fluvoxamina (300 mg) por pelo

menos 6 semanas foi significativamente superior ao de pacientes com TOC não

medicados. Portanto, pode se supor que o WCST seria um teste particularmente

“vulnerável” aos efeitos dos inibidores de recaptação da serotonina (IRS) e que a

inclusão de pacientes medicados nos diversos estudos poderia “mascarar” uma

disfunção do CPFDL.

Em um estudo recente, Andrés et al (2007) não encontraram disfunção

executiva em crianças e adolescentes com TOC, sugerindo que alguns sintomas

neuropsicológicos apresentados pelos pacientes com TOC não emergiriam até que o

sistema pré-frontal “amadurecesse”, o que ocorreria apenas no final da adolescência

ou mais tarde. Por outro lado, os mesmos autores encontraram, em sua amostra,

crianças e adolescentes que exibiam déficits na organização, memória visual e na

velocidade, sugerindo que estas disfunções seriam independentes de uma

sintomatologia depressiva.

O grupo de Menzies et al (2007), ao investigar um possível “endofenótipo” do

TOC (i.e. uma característica biológica transmissível geneticamente e subjacente ao

fenótipo psiquiátrico), observaram que houve um comprometimento de controle

inibitório motor predominantemente no grupo de pacientes com TOC e seu familiares,

comparados aos controles saudáveis, achado que foi significativamente associado à

redução de substância cinzenta em regiões orbitofrontal e frontal inferior direita e

aumento de substância cinzenta no cíngulo, em regiões parietais e em regiões

estriatais, a partir da observação, em conjunto, das imagens obtidas de ressonância

magnética funcional dos indivíduos avaliados.

MEMÓRIA

Na grande maioria dos estudos neuropsicológicos de pacientes com TOC,

os resultados são compatíveis com comprometimento da memória não-verbal, i.e. da

capacidade de aprender, reter e evocar imagens ou objetos novos, especialmente

aqueles que não podem ser descritos facilmente com palavras (Mataix-cols., 2001).

Um comprometimento mnêmico mais global, incluindo a memória verbal, foi

observado em apenas alguns estudos (Martin et al., 1993; Deckersbach et al., 2000;

Zitterl et al., 2001).

Dentre os testes de memória não-verbal que são executados com dificuldades

por pacientes com TOC encontram-se a reprodução visual da Wechsler Memory Scale

(Christensen et al, 1992; Boone et al., 1991); o Stylus Maze Learning Test (Behar et

al., 1984; Cox et al. 1989); o Benton Visual Retention Test (Rosen et al., 1988;

Aronowitz et al., 1992; Cohen et al., 1996); a Signoret’s Memory Efficiency Battery

(Dirson et al., 1995); o Delayed Recognition Span Test (Savage et al., 1996); o Spatial

Recognition (Purcell et al., 1998 a,b); o Recurring Figures Test (Zielinski et al., 1991;

Tallis et al., 1999), o Corsi Block Tapping Test (Zielinski et al., 1991; Zitterl et al.,

2001; Boldrini et al., no prelo), a memória tardia no Repeatable Battery for the

Assessment of Neuropsychological Status (Aycicegi et al., 2003) e as condições de

recuperação imediata e tardia do RCFT (Cox et al., 1989; Boone et al., 1991; Savage

et al., 1999; Savage et al., 2000; Kim et al., 2002; Kim et al., 2003; Chin et al., 2004),

assim como um teste muito semelhante a este último, o Figure Recall Test (Tallis et

al., 1999).

Pelo menos três estudos controlados (Savage et al., 1999; Savage et al., 2000;

Shin et al., 2004) foram conduzidos com o objetivo de investigar se existiria uma

possível relação dinâmica entre disfunções executivas (em particular as chamadas

estratégias organizacionais) e o comprometimento das memórias verbal e não-verbal

em pacientes com TOC. O termo “estratégias organizacionais” refere-se ao processo

estratégico de “quebrar” e “organizar” as informações em componentes mais simples

(ou semanticamente relacionados) que sejam mais fáceis de serem apreendidos e

memorizados.

De acordo com estes estudos, pacientes com TOC, quando em situações

ambíguas e complexas (exemplificadas em laboratório pelo RCFT e pelo CVLT),

tendem a cometer erros estratégicos. Os pacientes focalizam excessivamente em

detalhes, não consideram a gestalt visual (no caso do RCFT) ou a possibilidade de

associações semânticas (no caso do CVLT) de uma determinada situação e têm

dificuldades em mudar o cenário cognitivo. Os poucos estudos existentes sugerem

que o comprometimento das memórias não-verbal e verbal apresentado por pacientes

com TOC é resultado de uma disfunção executiva primária, i.e. os pacientes não

sabem organizar as informações de forma a torná-las mais facilmente memorizáveis.

Mataix-cols et al. (2003) observaram que o comprometimento da memória não-verbal

no TOC associou-se, independentemente, a estratégias organizacionais improdutivas

durante a condição de cópia da RCFT e à presença de sinais não localizatórios no

exame neurológico (soft signs). De acordo com estes últimos autores, duas variáveis

poderiam então mediar, independentemente, um prejuízo da memória não-verbal em

pacientes com TOC: (1) um componente cognitivo, de organização e planejamento, e

(2) um componente motor, de coordenação de movimentos complexos.

Em um estudo com indivíduos normais submetidos à tomografia por emissão

de pósitrons, Savage et al. (2001) constaram que a execução de testes que envolviam

a utilização de estratégias organizacionais estava associada a um aumento do

metabolismo em córtex órbito-frontal. Mais recentemente, Choi et al. (2004)

encontraram uma correlação positiva entre o volume da substância cinzenta do córtex

órbito-frontal anterior esquerdo e o escore obtido na cópia da RCFT em pacientes

com TOC. Considerados em conjunto, estes achados sugerem que a disfunção do

CPFOM estaria associada ao comprometimento de estratégias organizacionais em

pacientes com TOC.

O grupo de Omori (2006) avaliou 53 pacientes com TOC (sendo eles divididos

entre 27 checadores e 26 lavadores compulsivos) através de uma extensa bateria

neuropsicológica que incluía testes como o WMS-R, o Stroop Test, as Trilhas A e B, o

Go/NoGo, o Wisconsin Card Sorting Task (WCST), o WAIS-R (Digit Symbol), a

fluência verbal (letras e categorias) e a Dual-task (versão em papel e caneta). Segundo

Omori et al (2006), os checadores apresentaram um desempenho deficitário no

Stroop, no Trilhas, no Go/NoGo (omissões) e na fluência verbal (categorias).

Também apenas entre os checadores houve uma correlação significativa entre o fator

de inibição e a memória geral. Assim, no grupo dos checadores, uma memória geral

pobre estava relacionada a déficits inibitórios. Desta forma, os autores concluíram que

os déficits na inibição podem causar déficits mnêmicos secundários, especialmente

nos checadores compulsivos.

Em dois outros estudos foram encontrados distúrbios mnêmicos de provável

origem fronto-estriatal (Jurado et al., 2001; Jurado et al., 2002). Jurado et al. (2001)

observaram que pacientes com TOC, quando comparados a controles, foram

incapazes de estimar a freqüência de palavras previamente ouvidas e que esta

incapacidade correlacionou-se ao comprometimento no desempenho de um teste

executivo (o COWAT), mas não ao de outro (o WCST). O mesmo grupo (Jurado et

al., 2002) constatou que pacientes com TOC, quando comparado a controles, tiveram

problemas na execução de uma tarefa de ordenação temporal (i.e. eram incapazes de

reproduzir adequadamente uma lista de palavras na seqüência original) e, ainda assim,

superestimaram seu desempenho e não reconheceram suas dificuldades. Neste estudo,

o comprometimento na ordenação temporal também correlacionou se com o

comprometimento no desempenho de um teste executivo (no caso, o número de

categorias e os erros perseverativos do WCST).

A memória implícita também tem sido investigada em alguns estudos em

pacientes com TOC (Wiggs et al., 1996; Foa et al., 1997; Rauch et al., 1997;

Deckersbach et al., 2002, Roth et al., 2004). A memória implícita seria aquela que

envolve uma recuperação não-intencional e sem o conhecimento consciente do

indivíduo, enquanto que memória explícita englobaria aquelas lembranças que

ocorrem de maneira intencional e consciente. Embora os estudos descritos não

tenham encontrado disfunções da memória implícita, Rauch et al. (1997) observaram

que pacientes com TOC “recrutam” estruturas normalmente envolvidas no

aprendizado explícito (lobos temporais mediais) durante tarefas de aprendizado

implícito, sugerindo que as estruturas responsáveis pela memória implícita (estriado

inferior) encontram-se disfuncionais nestes indivíduos. Além disso, Deckersbach et

al. (2002) constataram que pacientes com TOC tiveram uma deterioração do

aprendizado implícito ao executarem uma tarefa que envolve as memórias explícita e

implícita simultaneamente. Segundo os autores, o aumento da demanda de

aprendizado de informações explícitas impediria o recrutamento compensatório dos

lobos temporais mediais, resultando em prejuízo do aprendizado implícito.

Outras habilidades mnêmicas, algumas provavelmente relacionadas aos lobos

frontais, estão supostamente comprometidas no TOC e incluem a meta-memória, a

memória para ações, o viés mnêmico a monitorização da realidade e a memória

prospectiva (Shimamura et al., 1991; Nyberg et al., 2001; Knight et al., 1995; Muller

e Roberts, 2004; Cuttler et al., 2006).

A meta-memória é auto-avaliação que um indivíduo faz de sua capacidade

mnêmica. Pacientes com TOC têm menor confiança em sua memória (McNally et al.,

1993; MacDonald et al., 1997; Tuna et al., no prelo) e necessitam de maior vivacidade

de suas imagens mnêmicas para alcançar um estado de satisfação subjetiva completa

(Constans et al., 1995). No estudo de Hermans et al. (2003), os pacientes com TOC

apresentaram níveis reduzidos de confiança também em outras funções cognitivas, i.e.

nas suas memória para ações, na monitorização da realidade e na capacidade de

manter a atenção focalizada. Em um único estudo (Jurado et al., 2001), os pacientes

com TOC superestimaram seus desempenhos cognitivos ou, em outras palavras,

foram excessivamente confiantes em uma tarefa de ordenação temporal quando

comparados a controles. Moritz, et al (2006) avaliaram 27 sujeitos com TOC (sendo

17 checadores) e 51 participantes saudáveis, numa tarefa de origem de memória e

numa tarefa que visava avaliar se pacientes com TOC demonstrariam algum problema

com lembranças vívidas e conscientes. Pacientes com e sem checagem não

apresentaram diferenças, em relação aos controles, na acurácia da memória de origem

nem na meta-memória.

van den Hout e Kindt (2003)

demonstraram que indivíduos normais

desenvolvem problemas com a meta-memória (lembranças menos vívidas e

detalhadas e associadas à redução da confiança na memória) a medida que repetem

verificações em laboratório, sugerindo que os problemas mnêmicos de pacientes com

TOC podem ser na realidade secundários às compulsões.

A memória para ações seria a recordação da realização de determinados atos

prévios. Alguns estudos sugerem que as compulsões se devem a uma disfunção da

memória para ações. Segundo esta hipótese, pacientes com TOC verificariam

repetidamente as portas, janelas e gás por não se lembrarem de ter realizado estes atos

previamente. Otto (1992) ressalta que a realização do comportamento repetitivo de

checagem provavelmente faz a “confirmação mnêmica” ainda mais difícil: o paciente

com TOC precisa não somente recuperar a última checagem completada, como

também, discriminar esta última checagem, das respostas de checagem anteriormente

emitidas. Até o momento, os resultados das avaliações da memória para ações em

pacientes com TOC têm sido contraditórios, observando-se em alguns estudos o

comprometimento desta habilidade (Ecker and Engelkamp, 1995) e noutros, sua

preservação (MacDonald et al., 1997; Merckelbach and Wessel, 2000).

O viés mnêmico é o processo que favorece a recordação ou dificulta o

esquecimento de determinados eventos e tem sido amplamente demonstrado em

pacientes com TOC (Radomsky et al., 1999; Radomsky et al., 2001; Tolin et al.,

2002; Ceschi et al., 2003; Wilhelm et al., 1996). A fenomenologia utiliza o termo

“hipermnesia” para descrever a vivência destes pacientes (Reed, 1977). Enquanto

“lavadores compulsivos” apresentam um viés mnêmico para os objetos “sujos”

(Ceschi et al., 2003; Radomsky et al., 1999), “verificadores compulsivos”

caracterizam-se por um viés mnêmico positivo para as situações “ameaçadoras”,

particularmente situações onde o indivíduo acredita possuir elevados níveis de

responsabilidade (Radomsky et al., 2001). Nestas situações, o viés mnêmico de

pacientes com TOC está paradoxalmente associado a uma redução da confiança em

sua memória (Radomsky et al., 2001).

Investigando os aspectos clínicos relacionados ao víeis mnêmico observados

entre os checadores compulsivos, Foa et al (2002) também observaram uma

percepção de responsabilidade do perigo aumentada nos checadores, comparados a

um grupo de pacientes obsessivo-compulsivos não-checadores e a um grupo de

pacientes ansiosos. Supostamente, tal distorção na percepção de responsabilidade

faria com que os checadores sentissem a necessidade de “corrigir” periodicamente

situações potencialmente perigosas.

A monitorização da realidade é a capacidade que um indivíduo tem de

determinar se uma determinada ação foi apenas imaginada ou verdadeiramente

realizada. Enquanto Rubinstein et al. (1993) e Ecker e Engelkamp (1995)

descreveram resultados compatíveis com o comprometimento desta habilidade, outros

autores não encontraram diferenças entre pacientes com TOC e controles saudáveis

(MacNally et al., 1993; Merckelbach and Wessel., 2000), mesmo com relação à

monitorização da realidade durante ações relacionadas com a temática do TOC

(Constans et al., 1995; Hermans et al., 2003). Surpreendentemente, Brown et al.

(1994) observaram que pacientes com TOC possuem uma capacidade ainda melhor de

monitorar a realidade do que aquela de controles normais.

Um estudo recente realizado por Cuttler et al (2006), em que participaram 126

estudantes não-graduados (classificados em 40 pouco checadores, 41 médico

checadores e 45 muito checadores), os grupos de checagem elevada e média

apresentaram um pior desempenho que o grupo de checagem baixa em uma tarefa de

memória episódica prospectiva (e.g. lembrar de realizar uma ação previamente

planejada), corroborando a tradicional teoria do déficit mnêmico em checadores

compulsivos. Os autores do referido estudo ainda sugerem que os déficits nas

memórias prospectiva e retrospectiva trabalham em conjunto na produção e

manutenção da tendência da checagem compulsiva.

HABILIDADES VISOESPACIAIS

Entre as disfunções cognitivas mais consistentemente identificadas no TOC

encontram-se o comprometimento das funções visoespaciais e visoconstrutivas,

entendidas como a capacidade de perceber ou manipular objetos no espaço

bidimensional ou tridimensional (Mataix-cols., 2001). Testes visoespaciais ou

visoconstrutivos são aqueles que envolvem desenhar ou manipular objetos em duas ou

três dimensões para reconstruir um determinado modelo original. Alguns testes nem

sequer requerem a percepção visual per se, somente a habilidade de manipular objetos

com os olhos fechados, como o Tactual Performance Test. Os testes visoespaciais são

complexos e requerem a integração de diferentes funções, ainda que compartilhem o

componente de raciocínio espacial. Diversos autores têm observado que pacientes

com TOC executam com dificuldade algumas destas tarefas, incluindo o subteste dos

cubos do WAIS (Hollander et al., 1993; Head et al., 1989; Christensen et al., 1992;

Kim et al., 2002), o Road Map Test of Direction Sense (Behar et al., 1984; Cox et al.,

1989; Head et al., 1989), o Matching Familiar Figures Test (Aronowitz et al., 1994),

o Tactual Performance Test (Christensen et al., 1992; Flor-Henry et al., 1979; Insel et

al., 1983), o Hooper Visual Organization Test (Boone et al., 1991), o Mental

Rotations Test (Savage et al., 1999) e a condição de cópia da RCFT (Behar et al.,

1984; Cox et al., 1989; Boone et al., 1991).

A relação entre as disfunções executivas e as habilidades viso-espaciais foi

objeto de poucos estudos até o momento. Head et al. (1989) observaram que pacientes

com TOC só têm dificuldades em tarefas visoespaciais que envolvem um componente

executivo (Block Design) ou a manipulação mental de informações não-verbais

(WCST). De maneira semelhante, Purcell et al. (1998 a,b) demonstraram que

pacientes com TOC têm uma disfunção da memória operante espacial (um subteste do

CANTAB). Na mesma linha de raciocínio, Mataix-cols (2001) notou que, se

examinarmos detalhadamente outros testes visoespaciais realizados com dificuldades

por pacientes com TOC, como o Road Map Test of Direction Sense ou o Mental

Rotations Test, chegaremos à conclusão de que eles também possuem um forte

componente executivo, envolvendo manipulação mental de informações espaciais.

Estes achados tornam-se particularmente interessantes quando consideramos

que, em um estudo com tomografia por emissão de pósitrons em indivíduos normais,

foi observada uma ativação do córtex pré-frontal dorso-lateral durante uma tarefa de

memória de trabalho espacial (Owen et al., 1996). No estudo de Van der Wee et al.

(2003), o comprometimento da memória de trabalho espacial de pacientes com TOC

associou-se a uma hiperatividade não do córtex pré-frontal dorso-lateral, mas do

córtex pré-frontal medial (cíngulo anterior). É possível que o aumento da atividade

nesta região tenha sido compensatório. Em resumo, os poucos estudos existentes

sugerem que o comprometimento visoespacial observado em pacientes com TOC é o

resultado de uma disfunção executiva primária. Além disso, é possível que esta

disfunção envolva o CPFDL.

PREDITORES NEUROPSICOLÓGICOS DE RESPOSTA ÀS DIVERSAS

INTERVENÇÕES TERAPÊUTICAS

A utilização de testes neuropsicológicos capazes de identificar ou de prever

quais pacientes com TOC responderiam a um dado tipo de intervenção terapêutica

seria um grande avanço, poupando a estes indivíduos tempo e sofrimento. Até o

momento, poucos estudos foram conduzidos com este objetivo.

Inibidores da recaptação da serotonina

Em uma investigação realizada na era “pré-inibidores seletivos de recaptação

da serotonina”, Malloy (1987) encontrou, em um grupo de 17 pacientes com TOC,

comprometimento do desempenho em dois subtestes do WCST (respostas

perserverativas e categorias completadas) e preservação do desempenho em testes de

atenção (Digits Forward e Letter Vigilance) e de inteligência (WAIS-R). Após a

avaliação dos escores individuais, o subgrupo com comprometimento do desempenho

no WCST (n = 8) foi considerado pelos seus clínicos como mais psicótico, com

menores níveis de funcionamento, menor inteligência, e pior prognóstico (muito

embora o autor não tenha definido quais foram os tipos de tratamento utilizados).

Em contraste, Fontenelle et al. (2001) também em um estudo não controlado

(mas prospectivo e que utilizou inibidores da recaptação da serotonina (IRS) em doses

elevadas por 10 semanas e critérios objetivos de resposta ao tratamento), observaram

que um pior desempenho dos pacientes com TOC nos parâmetros “erros

perseverativos” e “categorias completadas” do WCST (indicativos de

comprometimento da capacidade de mudança do cenário cognitivo) associou-se a

uma melhor resposta ao tratamento. Os autores discutiram seus achados à luz

daqueles descritos por Hollander e Wong (1995), que encontraram uma estreita

relação entre o comprometimento da capacidade de mudança do cenário cognitivo

(avaliada com o Trail Making Test) e uma resposta embotada da prolactina à infusão

de meta-clorofenilpiperazina, um agonista serotoninérgico. Fontenelle et al. (2001)

sugeriram que os pacientes com TOC que exibiam comprometimento da capacidade

de mudança do cenário cognitivo (e, por conseguinte, o tônus serotoninérgico

alterado) responderiam melhor ao tratamento com medicações serotoninérgicas.

Em um estudo conduzido por Cavedini et al. (2002), o desempenho de 34

pacientes com TOC no Iowa Gambling Task (IGT), uma tarefa que simula a tomada

de decisões na vida real e é supostamente sensível à disfunção órbito-medial, foi

comparado ao de 34 indivíduos saudáveis e ao de 16 pacientes com transtorno do

pânico. Os pacientes com TOC obtiveram piores resultados do que os outros dois

grupos. Quando pacientes com TOC que responderam aos IRS foram comparados aos

não respondedores observou-se que os respondedores alcançaram um desempenho

semelhante ao de indivíduos saudáveis, enquanto os não respondedores obtiveram um

maior comprometimento do desempenho da tarefa em comparação aos demais grupos.

Cavedini et al. (2002) sugeriram que a presença de uma disfunção do córtex órbito-

frontal estaria associada a uma pior resposta ao tratamento com medicações

serotoninérgicas.

Em seguida, o grupo de Cavedini et al. (2004) investigou o valor do

desempenho no IGT como critério para a seleção de um tipo específico de abordagem

farmacoterápica de pacientes com TOC, i.e. um IRS isoladamente vs. um IRS

associado a um antipsicótico. Neste trabalho, 20 pacientes com TOC e desempenho

pré-tratamento comprometido no IGT foram randomizados para um grupo a ser

tratado com fluvoxamina e risperidona (n=10) e um outro a ser tratado com

fluvoxamina e placebo (n=10). Um terceiro grupo de pacientes com TOC com

desempenho preservado no IGT pré-tratamento foi tratado com fluvoxamina e

placebo (n=10). O período de tratamento total foi de 12 semanas. Após o tratamento,

os pacientes foram reavaliados com o IGT. Cavedini et al. (2004) encontraram dois

resultados principais: (1) pacientes com desempenho comprometido no IGT mas

tratados com fluvoxamina e risperidona responderam de maneira semelhante a

pacientes com desempenho preservado no IGT e tratados com fluvoxamina

isoladamente (ambos os grupos responderam melhor do que os pacientes com

desempenho comprometido no IGT e tratados somente com fluvoxamina), e (2) o

número de pacientes com desempenho preservado no IGT após o tratamento não foi

significativamente dentre pacientes com desempenho pré-tratamento comprometido

no IGT tratados com fluvoxamina e risperidona e pacientes com desempenho

preservado no IGT e tratados com fluvoxamina isoladamente.

Nielen e Den Boer (2003) compararam o desempenho de 19 pacientes com

TOC ao de 24 indivíduos saudáveis na Cambridge Neuropsychological Test

Automated Battery. Pacientes com TOC caracterizaram-se por comprometimento da

capacidade de planejamento, da memória espacial e da velocidade motora, sugestivos

de disfunção do CPFDL. Os pacientes que não responderam ao tratamento com

fluoxetina por 12 semanas foram aqueles que obtiveram mais erros de interferência no

Stroop Test, o que é consistente com uma maior disfunção do CPFOM (Nielen e Den

Boer, 2004; Fontenelle et al., 2004).

Terapia de exposição e prevenção de respostas

A idéia de que disfunções neuropsicológicas possam ser úteis para prever

resposta à terapia de exposição e prevenção de respostas do TOC é derivada de

diversas observações (Moritz et al., no prelo). Primeiro, o comprometimento do

pensamento abstrato-lógico e da memória pode limitar a capacidade do paciente

entender e lembrar de questões discutidas durante as sessões de terapia cognitivo-

comportamental. Segundo, alguns padrões de disfunção executiva, como a

perseveração e o pensamento concreto, podem reduzir a capacidade do paciente de

transferir para o cotidiano habilidades adquiridas nas sessões. Terceiro, existe uma

crescente literatura indicando que a disfunção neuropsicológica é um importante

determinante de problemas com o funcionamento diário (e.g., estado empregatício,

relações sociais) em outros transtornos psiquiátricos (esquizofrenia, por exemplo).

Além disso, é razoável supor que problemas com o funcionamento diário possam

contribuir para piora da psicopatologia e resistência ao tratamento. Por último, a

disfunção neuropsicológica tem sido considerada um suposto fator de vulnerabilidade

para o desenvolvimento do TOC. Se isto for verdadeiro, pacientes com

comprometimento neuropsicológico grave podem se beneficiar de programas de

tratamento especializado que combinem elementos da terapia cognitivo-

comportamental e da reabilitação cognitiva.

Sieg et al.(1999) compararam o perfil cognitivo de 13 pacientes com TOC que

responderam ao tratamento cognitivo-comportamental por 9 semanas (“major

responders”) ao de 11 pacientes que não responderam adequadamente a tal

intervenção (“minor responders”). Os “minor responders” caracterizaram se por pior

desempenho no Visual Paired Associated Learning e no COWAT, tanto antes quanto

após o tratamento.

Bolton et al.(2000)

estudaram o desempenho cognitivo de 35 pacientes com

TOC antes e após 8 a 12 sessões semanais de terapia cognitivo-comportamental.

Neste estudo, foram empregados o Block Design, o Benton Visual Retention Test, a

RCFT, o Road Map Test of Direction Sense, o WCST e o COWAT-letras. Não foi

observada nenhuma correlação entre os resultados nos testes cognitivos antes do

tratamento e o decréscimo dos escores no Y-BOCS.

Moritz et al. (no prelo) avaliaram as funções cognitivas de 138 pacientes com

TOC antes de um tratamento cognitivo-comportamental multimodal que incluiu

exposição e prevenção de respostas, treinamento de habilidades sociais, resolução de

problemas e manejo de estresse. Cerca de 60% dos pacientes encontravam-se

medicados (na maioria das vezes com IRS) antes da terapia. Os testes utilizados

foram o Vocabulary Test, o TMT A e B, o Digit Span, o Creative Verbal Fluency, o

WCST, o Delayed Alternation Test (DAT), e um questionário para mensuração de

problemas atentivos subjetivos [incluindo o Fragebogen Erlebter Defizite der

Aufmerksamkeit (FEDA)]. Pacientes que não responderam ao tratamento cognitivo-

comportamental multimodal caracterizaram-se por uma tendência (p < 0.1) a um pior

desempenho no DAT, indicativo de um possível envolvimento do CPFOM. Já os

pacientes cujas compulsões não responderam ao tratamento caracterizaram-se por

maior tempo necessário para execução do TMT A e uma maior freqüência de erros

perseverativos no WCST.

CONSEQÜÊNCIAS NEUROPSICOLÓGICAS DAS DIVERSAS

INTERVENÇÕES TERAPÊUTICAS

Diversos estudos investigaram o efeito dos IRS, da terapia cognitivo-

comportamental (exposição e prevenção de respostas) e das “abordagens

neuroanatômicas” (neurocirurgia funcional e estimulação cerebral profunda) sobre as

funções cognitivas de pacientes com TOC.

Inibidores da recaptação da serotonina

Após a publicação, há mais de quinze anos, do caso de um paciente com TOC

que desenvolveu uma síndrome frontal resultante do uso de fluoxetina (Hoehn-Saric

et al., 1991), diversos estudos foram conduzidos com o objetivo de elucidar o real

efeito dos medicamentos antiobsessivos sobre as funções cognitivas de pacientes com

TOC.

Em alguns estudos transversais, nos quais pacientes com TOC em uso de

medicação foram comparados a pacientes não medicados, não foram encontradas

diferenças significativas entre os grupos (Purcell et al., 1998 a,b; Savage et al., 1999).

Entretanto, em outras investigações, sugeriu se que os IRS poderiam na realidade

melhorar o desempenho de pacientes com TOC em tarefas neuropsicológicas

(Abbruzzese et al., 1995) ou talvez até protegê-los dos efeitos deletérios de outros

psicofármacos sobre as algumas funções cognitivas (e.g. aquelas avaliadas pelo

WCST) (Mataix-cols et al., 2002). Por exemplo, enquanto Abbruzzese et al. (1995)

observaram que pacientes com TOC em uso de IRS tinham um melhor desempenho

no WCST, Mataix-cols e colaboradores (2002) notaram que pacientes com TOC em

uso de IRS e benzodiazepínicos tiveram um melhor desempenho no WCST do que

pacientes em uso de benzodiazepínicos isoladamente. Este efeito protetor não foi

notado no desempenho de outras tarefas. Pelo contrário, dentre os pacientes que

estavam medicados com benzodiazepínicos, aqueles em uso de IRS tiveram tempo de

reação mais lento do que os pacientes que não estavam em uso de IRS.

Antipsicóticos atípicos

No estudo de Cavedini et al. (2004), somente os pacientes que foram tratados

com fluvoxamina e risperidona, e não aqueles tratados somente com fluvoxamina,

melhoraram o desempenho no IGT após o tratamento. De Geus et al (2007)

investigaram os efeitos da adição do uso de outro antipsicótico atípico (quetiapina) no

tratamento com IRS dos pacientes com TOC no que tange às funções cognitivas. Os

autores utilizaram diferentes testes neuropsicológicos, como o Stroop, Trilhas, a

RCFT e o WCST, dentre outros, na linha de base e após 8 semanas de tratamento.

Concluíram que o acréscimo de quetiapina não traz maiores efeitos no funcionamento

cognitivo, embora alguma dificuldade na manutenção do cenário cognitivo no teste do

WCST tenha sido encontrada após o uso do antipsicótico.

Terapia de exposição e prevenção de respostas

Bolton et al. (2000) estudaram o perfil cognitivo de pacientes com TOC antes

e após o tratamento cognitivo-comportamental. Encontraram melhora do desempenho

no WCST (erros perseverativos) e no COWAT. Já o desempenho no Road Map Test

of Direction Sense, no Block Design, na RCFT, e no Benton Visual Retention Test

permaneceu inalterado.

Katrin et al (2006) realizaram um estudo avaliando o desempenho cognitivo

antes e após 12 semanas de terapia cognitivo-comportamental e concluíram que as

disfunções cognitivas dos pacientes com TOC podem melhorar durante o curso do

tratamento psicoterápico. Houve uma melhora significativa nos testes de memória

não-verbal, de troca de cenário e flexibilidade, e em tarefa que avaliava o

comportamento auto-guiado. Respondedores ao tratamento apresentaram desempenho

significativamente melhor nas recuperações imediata e tardia da RCFT, quando

comparados aos não-respondedores à terapia.

Neurocirurgia funcional

As intervenções neurocirurgicas permanecem como alternativas

terapêuticas viáveis em pacientes com TOC refratário aos tratamentos clínicos

habituais (Greenberg et al., 2000). No entanto, devido à falta de estudos controlados,

não há um consenso quanto a melhor técnica, i.e. aquela que está associada a uma

maior redução da intensidade dos sintomas e a uma menor freqüência de efeitos

indesejáveis, dentre os quais as disfunções cognitivas. A escolha da técnica por um

determinado centro tem sido amplamente determinada por fatores ligados à tradição e

às preferências das equipes responsáveis por um dado tipo de intervenção.

Até o momento, os procedimentos cirúrgicos utilizados com maior

freqüência para o tratamento do TOC refratário são a cingulotomia (lesão no fascículo

do cíngulo), a capsulotomia anterior (interrupção das fibras fronto-talâmicas através

de uma lesão na perna anterior da capsula interna), a tractotomia subcaudada

(interrupção das fibras fronto-talâmicas através de uma lesão na substantia

innominata), a leucotomia límbica (combinação de cingulotomia e tractotomia

subcaudada) (Greenberg et al., 2000) ou pequenas variações desses procedimentos

(Irle et al., 1998).

No estudo de Kim et al. (2003), quatorze pacientes tiveram suas funções

cognitivas examinadas antes e um ano após a realização de cingulotomia. Com o

tratamento, não foram observados comprometimentos no desempenho cognitivo dos

pacientes em diversas áreas como inteligência (WAIS), memória e habilidades

visoespaciais (RCFT), memória verbal (Hopkins Verbal Learning Test) e funções

executivas (WCST e COWAT). Ao contrário, alguns resultados do WCST (número

total de erros, respostas perseverativas e erros perseverativos) melhoraram após o

tratamento.

Nyman e Mindus (1995) investigaram as funções cognitivas de 10 pacientes

com transtornos de ansiedade “intratáveis” (sendo cinco com TOC) antes e após a

capsulotomia anterior. Um ano após o procedimento, o desempenho do grupo na

maioria dos testes permaneceu na faixa da normalidade. Foi observada, inclusive,

uma melhora significativa dos resultados obtidos no Tactual Performance Test (que

avalia memória e funções táteis). Quando os pacientes foram avaliados em conjunto,

houve uma aparente ausência de efeitos deletérios da capsulotomia sobre a cognição.

Entretanto, quando os pacientes foram avaliados individualmente, foram encontrados

decréscimos significativos no desempenho do WCST em cinco indivíduos. Um destes

pacientes apresentou um declínio maciço da performance neste teste (com um excesso

de erros perseverativos) e desenvolveu uma psicose paranóide. Não foi possível

identificar nenhum fator pré ou pós-operatório associado a um maior risco de declínio

cognitivo.

Posteriormente, o mesmo grupo (Nyman et al., 2001) comparou o

desempenho de pacientes com TOC candidatos a capsulotomia anterior ao de

pacientes com TOC já tratados. Ambos os grupos tiveram desempenhos que variavam

entre o normal e o subnormal na maioria dos testes. Entretanto, em um subgrupo de

pacientes operados que não completou todas as categorias do WCST, foi observada

uma correlação entre o tempo decorrido após a cirurgia e o número de categorias

completadas. Portanto, é possível que em alguns pacientes com TOC refratário, as

funções executivas sejam afetadas negativamente, embora transitoriamente, pela

capsulotomia.

Cumming et al. (1995) compararam o desempenho neuropsicológico de 17

pacientes com TOC submetidos a uma variedade de intervenções neurocirúrgicas

(incluindo a leucotomia límbica, a tractotomia subcaudada e a cingulotomia) ao de 17

pacientes com TOC pareados por idade, idade de início e gravidade do TOC, dentre

outras variáveis. Embora os grupos não tenham diferido em termos intelectuais e

mnêmicos, o grupo tratado cirurgicamente apresentou um desempenho no WCST

inferior ao do grupo controle, com um número significativamente menor de categorias

completas.

Irle et al. (1998) estudaram retrospectivamente 16 pacientes com TOC

submetidos a três tipos de leucotomia frontal bimedial, i.e. lesões frontais

ventromediais isoladas ou em associação a lesões no estriado ventral ou no córtex pré-

frontal dorsolateral. A melhor resposta foi obtida com a cirurgia envolvendo uma

lesão adicional no estriado ventral. Em comparação com um grupo de pacientes com

TOC grave, mas não operados, pacientes com lesões frontais ventromediais isoladas

tiveram um desempenho inferior no Emotional Sorting Task, pacientes com lesões

adicionais no estriado ventral alcançaram menos categorias no WCST, e pacientes

com lesões adicionais no córtex pré-frontal dorsolateral obtiveram piores escores no

WAIS não-verbal, na evocação imediata do Wechsler Memory Scale, no Trail Making

Test (A e B) e no Paired Associate Learning Task.

Em um estudo mais recente sobre os efeitos cognitivos da cingulotomia

(bilateral anterior), Jung et al (2006) concluíram que tal procedimento era efetivo no

tratamento do TOC refratário e nenhum efeito adverso na cognição havia sido

encontrado no seguimento após dois anos de realização da intervenção.

Estimulação cerebral profunda

Gabriels et al. (2003) estudaram o perfil cognitivo de três pacientes com

TOC refratário antes e um ano após a estimulação cerebral profunda da perna anterior

da capsula interna. Dois pacientes responderam satisfatoriamente ao tratamento

(decréscimo de pelo menos 35% dos escores iniciais no Y-BOCS). Foi observada uma

melhora do desempenho cognitivo em alguns testes: em todos pacientes foi observada

melhora da cópia do Digit Symbol e, em um caso, foi observada melhora do

desempenho na Raven Progressive Matrices, no Paced Auditory Selective Attention

Test, no RCFT e na cópia do Digit Symbol. Apesar da melhora em algumas funções,

todos os pacientes passaram a ter mais dificuldades com a execução do WCST (maior

número de erros perseverativos).

Em um estudo recente utilizando a estimulação cerebral profunda como

uma possível estratégia de tratamento em pacientes com TOC refratário, Greenberg et

al (2006) não encontraram nenhum declínio cognitivo significativo após o tratamento.

As análises dos autores revelaram melhoras significativas na recuperação de pequenas

histórias durante a estimulação crônica. No que se refere aos sintomas clínicos, foi

observada melhora significativa no humor, na ansiedade, na espontaneidade, na

fluência verbal, na expressividade, juntamente com um aumento do estado de alerta e

na freqüência cardíaca.

DISFUNÇÕES NEUROPSICOLÓGICAS DO TIPO TRAÇO VS. ESTADO

A evolução do desempenho cognitivo de pacientes com TOC também permitiu

identificar disfunções do tipo “estado” e “traço”, especialmente naqueles pacientes

que eram subtipos a diferentes tipos de tratamento simultaneamente. No estudo de

Kim et al. (2002), um grupo de 39 pacientes com TOC apresentou um desempenho

inferior ao de 31 indivíduos saudáveis na evocação imediata e tardia da RCFT, na

parte A do Trail Making Test, no COWAT (tanto letras quanto categorias), e no Block

Design. Após quatro meses (durante os quais o grupo com TOC foi tratado com IRS,

dentre outros medicamentos), somente o desempenho da parte A do Trail Making

Test, do Block Design, e do COWAT-letras melhorou com o tratamento. Os pacientes

mantiveram seu desempenho comprometido na evocação imediata e tardia do RCFT e

no COWAT- categorias, apesar de terem apresentado uma melhora significativamente

maior do que aquela demonstrada por controles. Pacientes e controles saudáveis não

diferiram no desempenho do WCST inicialmente, e ambos os grupos melhoraram seu

desempenho na segunda avaliação.

Em um outro estudo, Kang et al. (2003) avaliaram o perfil cognitivo e as taxas

de metabolismo cerebral de glicose de 10 pacientes com TOC antes e após o

tratamento com IRS (associados a antipsicóticos ou benzodiazepínicos em 3

pacientes). Após o tratamento por 4 meses, foram observadas (1) melhora

significativa do desempenho na evocação imediata e tardia da RCFT, (2) manutenção

dos escores no COWAT-letras e categorias, na parte B do Trail Making Test, na cópia

do RCFT e nos erros perseverativos do WCST; e (3) mudanças metabólicas

significativas em múltiplas áreas cerebrais, envolvendo circuitos fronto-subcorticais e

parieto-cerebelares. A melhora dos escores da evocação imediata e tardia do RCFT se

correlacionou significativamente com melhora do metabolismo da glicose em diversas

estruturas do hemisfério direito (putâmen, hipocampo e cerebelo).

Nielen e Den Boer (2003) compararam o desempenho de 19 pacientes com

TOC na Cambridge Neuropsychological Test Automated Battery foi comparado ao de

24 indivíduos saudáveis antes e após o tratamento, no caso, a fluoxetina. Os pacientes

com TOC caracterizaram-se por comprometimento da capacidade de planejamento,

da memória espacial e da velocidade motora, sugestivos de disfunção do CPFDL na

linha de base. Após 12 semanas de tratamento com fluoxetina, não foi constatada

nenhuma mudança significativa das funções cognitivas, sugerindo que a disfunção do

CPFDL é um traço de pacientes com TOC.

Mais recentemente, Bannon et al (2006) investigaram se as disfunções

executivas evidenciadas nos pacientes com TOC seriam déficits de estado ou traço e

verificaram que os déficits na mudança de cenário cognitivo e de inibição se

mantinham mesmo após a remissão dos sintomas. Os autores não verificaram déficits

no planejamento, na fluência verbal ou na memória de trabalho nos grupos de

pacientes com TOC (atual ou em remissão), sugerindo que os déficits executivos são

específicos e do tipo traço.

REABILITAÇAO COGNITIVA

Um tipo de intervenção terapêutica que poderia ser útil, mas que ainda não

foi estudado amplamente, é a reabilitação cognitiva. Savage (1998), por exemplo,

sugeriu que pacientes com TOC poderiam aprender a melhorar suas funções

executivas avaliando situações de uma maneira mais global, recuperando

secundariamente outras habilidades cognitivas (como a memória e as habilidades

visoespaciais) e, finalmente, reduzindo a intensidade dos sintomas obsessivo-

compulsivos. Este tipo de tratamento poderia ser utilizado como potencialização dos

efeitos da farmacoterapia ou da terapia cognitivo-comportamental.

Em um estudo recente avaliando os efeitos do treino cognitivo, focalizando

no aprimoramento de estratégias organizacionais, em pacientes com TOC, Park, et al

(2006) verificaram que esta modalidade de intervenção pode ser efetiva para melhorar

o funcionamento mnêmico. Durante um período de 5 semanas, os pesquisadores

ofereceram nove sessões (de sessenta minutos cada) que tinham como objetivo

aprimorar as estratégias organizacionais dos pacientes com TOC e, para isso,

utilizaram como material os cubos, comumente utilizados nos testes de inteligência, e

um treino nas habilidades de resolução de problemas, utilizando-se de situações do

dia-a-dia.

Após o treino, os pacientes obtiveram melhor desempenho na cópia e nas

recuperações (imediata e tardia) da RCFT, comparados ao grupo controle. Nenhuma

diferença foi encontrada, entre os grupos, após o treino, no desempenho do CVLT.

Desta forma, os autores concluíram que o treino cognitivo, baseado em estratégias

organizacionais, aprimora a memória visual e aliviam os sintomas clínicos do TOC

(tais pacientes também apresentaram um decréscimo na pontuação do Y-BOCS após

o treinamento cognitivo).

Em um outro estudo envolvendo 35 pacientes com TOC e 36 controles,

alguns participantes foram treinados na cópia e recuperação da Figura de Taylor

(similar à RCFT) e outros não (Buhlmann et al., 2006). Buhlmann et al (2006)

verificaram que tanto os pacientes quanto os controles treinados melhoraram na

organização e na memória visual, comparados aos indivíduos que não foram

treinados. Além disso, após o treino, os pacientes com TOC apresentaram estratégias

organizacionais significativamente superiores a de controles no registro da cópia da

RCFT, sugerindo que o comprometimento organizacional dos pacientes com TOC

afeta primariamente a habilidade de utilizar espontaneamente estratégias diante de

informações complexas e ambíguas mas também que a habilidade para implementar

tais estratégias está preservada quando são oferecidas tentativas adicionais.

SUBTIPOS E TRANSTORNOS DO ESPECTRO OBSESSIVO-COMPULSIVO

Como mencionado na seção introdutória do presente capítulo, evidências

crescentes apontam para a existência de diversos subtipos de transtornos obsessivo-

compulsivos. De fato, em diversos estudos neuropsicológicos, foram realizadas

tentativas de validação neuropsicológica de subtipos de TOC já amplamente

estudados do ponto de vista clínico e terapêutico, como aqueles baseados na idade de

início (Sobin et al., 2000; Rosário-Campos et al., 2001; Fontenelle et al., 2003), na

presença de tiques (Miguel et al., 2001), na presença de compulsões de acumulação

(Frost et al., 2000; Samuels et al., 2002; Saxena et al., 2002; Fontenelle et al., 2003) e

no gênero dos pacientes (Castle et al., 1995; Lensi et al., 1996; Bogetto et al., 1999;

Fontenelle et al., 2002).

Na tabela 1, o leitor encontra um resumo dos estudos neuropsicológicos que

investigaram a existência de diferentes subtipos do TOC. Estes estudos tendem a

validar diferentes fenótipos clínicos e neuropsicológicos do TOC (ver Tabela 1).

Enquanto muitos estudos neuropsicológicos têm contribuído para fortalecer as

evidências que sustentam a concepção de que o TOC representa uma entidade

diagnóstica distinta, do ponto de vista cognitivo, de outras patologias do sistema

nervoso central [segundo os parâmetros estabelecidos por Robins e Guze (1970) e

atualizados por Andreasen (1995)], evidências adicionais neuropsicológicas tem

contribuído para aproximar o TOC e transtornos outrora considerados independentes,

como o transtorno dismófico corporal e a tricotilomania. Estes transtornos

psiquiátricos associados, dentre outras características, à disfunções neuropsicológicas

semelhantes a do TOC, tem sido denominados transtornos do espectro obsessivo-

compulsivo. Estes transtornos apresentariam um padrão de disfunção executiva e

mnémica indistinguível de pacientes com TOC. Um resumo dos estudos que

comparam o perfil neuropsicológico de pacientes com TOC àquele de pacientes com

outros transtornos psiquiátricos encontra-se na tabela 2.

CONCLUSÕES

Ainda não existe um consenso quanto ao(s) tipo(s) exato(s) de disfunção

executiva envolvida(s) na fisiopatologia do TOC. No entanto, é provável que uma

disfunção desta natureza seja responsável, secundariamente, pelo comprometimento

da memória e das habilidades visoespaciais freqüentemente encontrado nestes

pacientes. Olley et al (2007) chamam a atenção para as cinco grandes possíveis

dimensões de sintomas do TOC como sendo fatores importantes de serem mais bem

estudados, uma vez que estudos apontam para padrões distintos de medidas

neurobiológicas e cognitivas dentre eles, além de possíveis diferenças nas respostas

aos tratamentos.

Os estudos sobre preditores de resposta ao tratamento farmacológico

merecem comentários adicionais. Uma resposta favorável ao tratamento com IRS

associou-se ao comprometimento da execução do WCST (sugestivo de disfunção em

CPFDL) em um estudo (Fontenelle et al., 2001), e a um melhor desempenho do IGT e

do Stroop Test (sugestivo de preservação da função do CPFOM) em outros dois

estudos [Cavedini et al. (2002) e Nielen e Den Boer (2003), respectivamente]. Este

perfil neuropsicológico é semelhante ao descrito em pacientes com transtorno

depressivo maior (Cavedini et al., 1998; Moritz et al., 2002) e sugere que os pacientes

que respondem ao tratamento com antidepressivos serotoninérgicos são aqueles

cognitivamente semelhantes à pacientes deprimidos. No entanto, esta ainda é uma

hipótese a ser testada. Curiosamente, enquanto que um desempenho desfavorável no

IGT parece estar associado a pior resposta ao tratamento com IRS isoladamente, a

introdução de risperidona em pacientes com TOC associou-se a melhora no

desempenho neste teste (Cavedini et al., 2004).

No geral, os achados obtidos em estudos longitudinais, antes e após o

tratamento com IRS (Kim et al., 2002; Kang et al., 2003; Nielen e Den Boer, 2003) ou

terapia cognitivo-comportamental (Bolton et al., 2000), sugerem que algumas

disfunções cognitivas associadas ao TOC seriam do tipo “traço” (e, por conseguinte,

mais resistentes ao tratamento farmacológico ou à exposição e prevenção de

respostas), enquanto outras seriam do tipo “estado” (mais facilmente manejáveis em

termos terapêuticos). Como os resultados são muito heterogêneos, não está claro

ainda quais seriam estas funções. A princípio, a existência de disfunções cognitivas

do tipo “traço” seria compatível com a hipótese de que uma disfunção cognitiva

poderia ser um fator de risco ou mesmo um endofenótipo do TOC, concorrendo

inclusive para o surgimento dos sintomas (Otto, 1992; Cottraux and Gerárd, 1998;

Savage, 1998; Menzies et al., 2007). Entretanto, os achados de van den Hout e Kindt

(2003), que observaram que a repetição de verificações pode resultar em disfunções

cognitivas (prejuízo da meta-memória), sugerem que o fenômeno inverso também

pode ser verdadeiro.

Já os estudos sobre a neurocirurgia do TOC, embora insuficentes e com

diversas falhas metodológicas, sugerem que a cingulotomia estaria associada a uma

menor possibilidade de que o paciente venha a desenvolver disfunções executivas

pós-cirurgicas. Talvez uma cirurgia que envolva uma estrutura previamente

disfuncional no TOC (i.e. o giro do cíngulo) não resulte em prejuízo cognitivo

adicional.

Estudos neuropsicológicos futuros devem fornecer dados adicionais que

confirmem ou refutem a existência de preditores de resposta ao tratamento em

pacientes com TOC, a existência de marcadores neuropsicológicos em indivíduos de

alto risco para o desenvolvimento do transtorno, e a possibilidade de utilizar

estratégias de reabilitação cognitiva como parte do tratamento anti-obsessivo.

Tabela 1: Alguns estudos neuropsicológicos com dados sobre a validação do TOC em relação à outros transtornos psiquiátricos

ESTUDOS AMOSTRA TESTES RESULTADOS

TOC vs. esquizofrenia

Bellini et al. (1988) 10 OC

10 ESQ

10 controles normais

Bateria Neuropsicológica de Luria-

Nebraska

ESQ com pior desempenho do que OC em 8 escalas

da bateria.

Abbruzzese et al.

(1997)

25 OC

25 ESQ

25 controles normais

WCST, OAT

ESQ com > no. de erros perseverativos no WCST do

que OC.

OC com > no. de erros perseverativos no OAT do

que ESQ.

Hoenig et al. (2002)

15 OC

16 ESQ

16 controles normais

Primming negativo

ESQ com pior desempenho (< quantidade de

primming negativo) do que OC.

Moritz et al. (2002) 25 OC

25 ESQ

25 DEP

70 controles normais

TMT, Stroop Test, WCST, Digit Span,

Verbal Fluency

ESQ com pior desempenho do que controles no TMT,

no Stroop Test, no WCST, no Digit Span Backward

e no Verbal Fluency.

OC com pior desempenho do que controles no TMT e

no Verbal Fluency.

Cavallaro et al.

(2003)

67 OC

11 ESQ

56 controles normais

The Gambling Task, WCST, Tower of

Hanoi

ESQ com pior desempenho no WCST (> no. de erros

perseverativos e < número de categoriascompletadas )

do que OC.

OC com pior desempenho no Gamblimg Task

(escolha de > no. de cartas desvantajosas) do que

ESQ.

Whitney et al.

(2004)

11 OC

26 ESQ ou ESQ-A

com OC

28 ESQ ou ESQ-A sem

The Gambling Task, WCST, RCFT, CVLT,

WAIS Block Design, TMT A

Não foram observadas diferenças estatisticamente

significativas entre os grupos no desempenho dos

testes utilizados.

TOC vs. transtorno

depressivo maior

Purcell et al. (1998) 30 OC

20 DEP

30 TP

30 controles normais

CANTAB Spatial Span, Spatial Working

Memory, Tower of London, Delayed

Matching to Sample Pattern

Recognition, Spatial Recognition,

Attentional Set-Shifting

OC com pior desempenho do que TP no Spatial

Working Memory (maior número de erros e pior

estratégia), no Spatial Recognition e (menor número

de acertos) e na Tower of London (mais lento nos

movimentos inicial e subseqüente).

DEP, e não OC, com pior desempenho do que

controles no estágio intradimensional do Attentional

Set-Shifting Task.

Cavedini et al.

(1998)

28 OC

29 DEP

Weigl’s Sorting Test, Verbal Fluency,

WCST, DAT, WMS

OC com pior desempenho do que DEP no DAT (> no.

de erros perseverativos).

Moritz et al. (2002) 25 OC

25 DEP

25 ESQ

70 controles normais

TMT, Stroop Test, WCST, Digit Span,

Verbal Fluency

DEP com pior desepenho do que controlesno TMT,

no Stroop Test, no WCST, no Digit Span Backward e

no Verbal Fluency.

Joel et al. (no prelo) 18 OC

16 PD

14 DEP

35 controles normais

Card Betting Task (Tarefa de

aprendizado implícito onde o

procesamento explícito compromete a

execução)

A maioria dos OC (15/18) e dos DP (14/16) não

completou a tarefa. DEP completaram a tarefa de

maneira semelhante a controles.

TOC vs. transtorno

bipolar

Deckersbach et al.

(2004)

30 OC

30 TB I

30 controles normais

CVLT

OC e TB I com pior desempenho do que controles na

evocação livre tardia e nas estratégias organizacionais

durante o aprendizado. TB I com pior desempenho do

que OC na evocação livre tardia e com melhor

desempenho que OC nas estratégias organizacionais.

TOC vs. transtornos de

ansiedade

Cohen et al. (1996) 65 OC

17 FS

32 controles normais

TMT, WAIS-R Digit Span, Digit Symbol,

Information, e Block Design, BVRT,

MFFT

FS com pior desempenho do que OC no TMT B.

Purcell et al. (1998) 30 OC

20 DEP

30 TP

30 controles normais

CANTAB Spatial Span, Spatial Working

Memory, Tower of London, Delayed

Matching to Sample Pattern

Recognition, Spatial Recognition,

Attentional Set-Shifting.

OC com pior desempenho do que TP no Spatial

Working Memory (maior número de erros e pior

estratégia), no Spatial Recognition e (menor número

de acertos) e na Tower of London (maior lentidão nos

movimentos inicias e subseqüentes).

Clayton et al. (1999)

17 OC

13 TP

14 controles normais

Test of Everyday Attention

OC com pior desempenho do que TP em tarefas de

atenção seletiva, de atenção sustentada e de mudança

do cenário atentivo do que TP.

Boldrini et al. (no

prelo)

25 OC

15 TP

15 controles normais

WCST, COWAT, RCFT, Facial

Recognition Test, Corsi Block Tapping

Task, Digit Span, Buscke-Fuld Selective

Remiding Test, Raven Colored

Progressive Matrices

OC com pior desepenho do que TP e controles no

RCFT , no Buscke-Fuld Selective Remiding Test, no

COWAT e no WCST (maior número de seleções

nulas). OC e TP com pior desempenho que controles

no Corsi Block Tapping Task..

Airaksinen et al. (no

prelo)

16 OC

32 FS

24 FE

7 TAG

175 controles normais

COWAT, TMT, Teste de Memória

Episódica

OC e TP com pior desempenho do que controles no

Teste de Memória Episódica e no TMT B.

FS com pior desempenho do que controles no Teste

de Memória Episódica.

TAG e FE sem disfunção neuropsicológica em

relação a controles.

TOC vs. transtornos

neurológicos

Hollander et al.

(1993)

37 OC

35 DP

WAIS Digit Span e Block Design, Stroop

Test

DP com pior desempenho do que OC nas partes B e C

do Stroop Test do que OC (> lentidão).

Coetzer et al. (2001)

13 OC

13 LCT

10 controles normais

SAWAIS, RCFT, Austin Maze

LCT com pior desempenho do que OC no SAWAIS

(menor QI) e no RCFT (estratégias organizacionais).

Siviero et al. (2002)

20 OC

13 disléxicos

16 controles normais

Dominância cruzada

Dominância cruzada mais freqüente em OC do que

em pacientes com dislexia

Joel et al. (no prelo) 18 OC

16 PD

14 DEP

35 controles normais

Card Betting Task (Tarefa de

aprendizado implícito onde o

procesamento explícito compromete a

execução)

A maioria dos OC (15/18) e dos DP (14/16) não

completou a tarefa. DEP completaram a tarefa de

maneira semelhante a controles.

TOC vs. transtornos do

espectro obsessivo-

compulsivo

Martin et al. (1993) 17 OC

11 tricotilomania

16 controles normais

WAIS Vocabulary e Block Design,

RMTDS, Room Test, Verbal Fluency,

Visual Reaction Time, Visual Search

Task, CVLT

O desempenho de OC não diferiu significativamente

do de pacientes com tricotilomania em nenhum dos

testes.

Stein et al. (1994) 34 OC

13 tricotilomania

16 controles normais

Face-hand test, confusão direita-

esquerda, desenho de um cubo.

O desempenho de OC não diferiu significativamente

do de pacientes com tricotilomania em nenhum dos

testes.

Coetzer e Stein

(1999)

11 OC

11 tricotilomania

11 controles normais

SAWAIS, Stroop Test, Austin Maze,

Hooper Visual Organization Test, RCFT

O desempenho de OC não diferiu significativamente

do de pacientes com tricotilomania em nenhum dos

testes.

Hanes (1998) 10 OC

14 transtorno

dismórfico corporal

14 ESQ

24 controles normais

Stroop Test, New Tower of London,

Verbal Fluency, RAVLT, RCFT, Purdue

Pegboard

O desempenho de OC não diferiu significativamente

do de pacientes com transtorno dismórifico corporal

em nenhum dos testes.

Nota: TOC = transtorno obsessivo-compulsivo; OC = pacientes com TOC; ESQ = pacientes com esquizofrenia; ESQ-A = pacientes com transtorno esquizoafetivo; DEP =

pacientes com depressão; TB I = pacientes com transtorno bipolar I; FS = pacientes com fobia social; TP = pacientes com transtorno do pânico; FE = pacientes com fobia

específica, TAG = pacientes com transtorno de ansiedade generalizada; DP = pacientes com doença de Parkinson; LCT = pacientes com lesão cerebral traumática; WCST =

Wisconsin Card Sorting Test; OAT = Objects Alternation Test; TMT = Trail Making Test; CANTAB = Cambridge Automated Neuropsychological Test Battery; DAT =

Delayed Alternation Test; WMS = Wechsler Memory Scale; WAIS-R = Weschsler Adult Inteligence Scale-Revised; BVRT = Benton Visual Retention Test; MFFT =

Matching Familiar Figures Test; SAWAIS = South African Weschsler Adult Inteligence Scale; RCFT = Rey Osterreith Complex Figure Test; RMTDS = Road Map Test of

Direction Sense; CVLT = California Verbal Learning Test; RAVLT = Rey Auditory Verbal Learning Test.

Tabela 2: Alguns estudos neuropsicológicos com dados sobre a validação de prováveis subtipos de TOC

AMOSTRA TESTES RESULTADOS

TOC de início

precoce

Behar et al. (1984) Dezesseis crianças e

adolescentes com TOC vs. 16

crianças e adolescentes

saudáveis.

RMDS, Stylus Maze, RWLT,

RCFT, Dihaptic Testing,

Reaction Time and two flash

threshold.

OC com pior desempenho do que

controles no Stylus Maze e no

RMDS.

Cox et al. (1989) Quarenta e duas crianças e

adolescentes com TOC vs. 35

crianças e adolescentes

saudáveis.

WCST, Stylus Maze Learning,

RMDS, RCFT, RAVLT, Visual

recognition threholds for words

and patterns, auditory tasks,

Dihaptic enconding task.

OC com pior desempenho que

controles no WCST, Stylus Maze

Learning, RMDS, RCFT e no

RAVLT.

Beers et al. (1999)

Vinte e uma crianças e adolescentes

com TOC não deprimidas vs. 21

crianças e adolescentes saudáveis.

WCST, Stroop Test, TMT,

COWAT, Tower of Hanoi, Go-

no-go, CVLT, WISC-III,

Grooved Pegboard.

OC não diferiram de controles no

desempenho de nenhum teste.

Cavedini et al.

(2001)

Cento e vinte e três adultos com

TOC (com diversas idades de

início) vs. 53 adultos saudáveis.

Tower of Hanoi

Escores no Tower of

hanoi/procedimento se

correlacionaram com a idade de

início mais precoce.

Henin et al. (2001) Trinta e sete adultos com TOC

de início precoce vs. 31 com

início tardio

RCFT, CVLT. OC com início precoce não diferiram

daqueles de início tardio no

desempenho de nenhum teste.

Roth et al. (2005) Vinte e um pacientes com TOC

de início precoce; 17 pacientes

com início tardio

WCST, SOPT, TMT, WMS-R,

CVLT, RCFT, WAIS-R Block

Design, Digit Span e Digit

Symbol, Purdue Pegboard e

dinamômetro manual

OC com início tardio obteve escores

mais baixos em medidas de função

executiva, atenção auditiva e

memória visual que o grupo de início

precoce dos sintomas

Hwang et al.

(2007)

Vinte e quarto pacientes com

TOC de início precoce; 24

pacientes TOC de início tardio;

24 adultos saudáveis

RCFT, COWAT; TMT; WCST;

K-WAIS

OC com início tardio tiveram pior

desempenho nas recuperações

imediata e tardia da RCFT e no

COWAT. Os controles e os pacientes

com início precoce não diferiram no

desempenho de nenhum teste

TOC associado a

tiques

Hartston e

Swerdlow (1999)

Setenta e seis adultos com TOC

vs. 76 controles saudáveis

Visuospatial Primming Task,

Stroop Test.

OC com tiques com > maior

facilitação do priming visoespacial

em comparação com OC sem tiques.

TOC diferentes

dimensões de

sintomas

Kyrios et al. (1999)

Cinqüenta e nove pacientes

com TOC

Cambridge Automated

Neuropsychological Test Battery

Em uma tarefa de reconhecimento,

os OC lavadores tiveram um

desempenho significativamente

melhor, enquanto que, numa tarefa

de planejamento, os OC checadores

demandaram um maior tempo para a

resposta motora, mas não para a

cognitiva, comparados aos demais

subtipos.

Hartl et al. (2001) Vinte e dois adultos com

acumulação (com e sem TOC)

vs. 24 adultos saudáveis.

RCFT, CVLT Acumuladores com pior evocação no

RCFT e no CVLT, e menor uso de

estratégias organizacionais eficazes

no RCFT, mas não no CVLT

(acumuladores com mais preservados

do que outros OC?).

Grisham et al.

(2005)

Trinta pacientes com

acumulação (com ou sem TOC)

vs. 30 pacientes com sintomas

mesclados vs. 30 pacientes não

clínicos

WASI Visual Memory Span and

Digit Span, Continuous

Performance Test-II, The

Gambling Task

Pacientes com acumulação

demonstraram maior lentidão, tempo

de reação mais variável, aumento da

impulsividade, maior dificuldade em

distinguir estímulos alvos e não-

alvos e pior atenção espacial

comparados aos outros dois grupos.

Lawrence et al.

(2006)

Trinta e nove pacientes com

TOC vs. 40 controles

WCST, The Gambling Task OC com acumulação mais grave

tiveram desempenho mais

comprometido no Gambling Task.e

OC com sintomas de

simetria/ordenação mais grave se

associaram desempenho mais

comprometido no WCST.

Cha et al. (2007) Vinte e três pacientes com TOC

lavadores vs. 24 pacientes com

TOC checadores vs. 20

controles saudáveis

WCST, RCFT, Hopkins Verbal

Learning Test, WAIS-R

OC checadores obriveram escores

significativamente mais baixos nas

recuperações imediata e tardia da

figura de Rey.

TOC baseado no

gênero

Aronowitz et al.

(1994)

Trinta e um adultos com TOC

vs. 22 adultos saudáveis (Vinte

homens com TOC vs. 10

homens saudáveis).

WAIS Information, Digit Span,

Block Design, Digit Symbol;

Stroop Test, TMT, BVRT,

MFFT.

OC com pior desempenho do que

controles no BVRT, no MFFT e no

TMT A e B. Homens com TOC com

pior desempenho que controles no

BVRT, no TMT B, e no Information,

Block Design, e Digit Symbol do

WAIS (homens com maior

comprometimento visoespecial e

visoconstrutivo?)

Zohar et al. (1999) Dezoito mulheres adultas com

TOC vs. 14 homens adultos

com TOC.

WCST, DAT, Raven’s Colored

ou Standard Progressive

Matrices.

Correlação entre a gravidade dos

sintomas obsessivo-compulsivos e

número de alternâncias no DAT

positiva em homens e negativa em

mulheres com TOC.

Fontenelle et al.

(dados não

publicados)

Doze mulheres adultas com

TOC vs. 8 homens adultos com

TOC.

WCST, The Gambling Task,

Tower of Hanoi, BADS,

COWAT, RCFT, CVLT, WAIS-

R Visual Reproduction, Digit e

Visual Span, Raven’s Progressive

Matrices.

Mulheres com pior desempenho do

que homens no Visual Reproduction,

no Digit Span e no Visual Span do

WAIS-R (mulheres com maior

comprometimento da memória

operante?)

Mataix-cols et al.

(2006)

Cinqüenta e seis pacientes com

TOC e 40 controles saudáveis

COWAT, Stroop test, WAIS-R

Digit Span Forward test.

Mulheres com TOC com pior

desempenho na fluência verbal que

os mulheres saúdaveis com TOC e

controles

Nota: TOC= transtorno obsessivo-compulsivo; RMDS= Road Map of Direction Sense; RWLT= Rey Word List Learning; RCFT= Rey-Osterreith Complex Figure Test; OC=

pacientes com TOC; WCST= Wisconsin Card Sorting Test; RAVLT= Rey Auditory Verbal Learning Test; TMT= Trail Making Test; COWAT= Controlled Oral Word

Association Test; CVLT= California Verbal Learning Test; WISC-III= Wechsler Intelligence Scale for Children-III; WAIS= Wechsler Adult Intelligence Scale-Revised;

BVRT= Benton Visual Retention Test; MFFT= Matching Familiar Figures Test; DAT= Delayed Alternation Test; BADS= Behavior Assessment of the Dysexecutive

Syndrome.

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113-7.

2.2) Artigo científico submetido à Psychological Medicine

COGNITIVE DYSFUNCTION IN “POST-TRAUMATIC” OBSESSIVE-

COMPULSIVE DISORDER

Manuela C. Borges

;

Daniela T. Braga

; Sandro Iêgo

; Carina C. D’Alcante

; Anita

Taub

; Ilduara Sidrim

; Maria Cristiana Machado

; Kátia Petribú

; Samantha Nunes

;

Paula Sanders

; Curt H. Menezes

; Aristides V. Cordioli

; Maria Conceição do

Rosário

; Mauro V. Mendlowicz

; Jair J. Mari

; Eurípedes Miguel

;

Leonardo F. Fontenelle

1,6

Running-Head: Cognition in PsT-OCD

______________________________________________________________

Instituto de Psiquiatria, Universidade Federal do Rio de Janeiro, Rio de Janeiro,

Brazil;

Departamento de Psiquiatria; Universidade Federal do Rio Grande do Sul,

Porto Alegre, Brazil;

Departamento de Psiquiatria, Universidade Federal da Bahia,

Salvador, Brazil;

Departamento e Instituto de Psiquiatria, Universidade de São

Paulo, São Paulo, Brazil;

Faculdade de Ciências Médicas, Universidade de

Pernambuco, Recife; Brazil;

Departamento de Psiquiatria e Saúde Mental,

Universidade Federal Fluminense, Niterói, Brazil;

Departamento de Psiquiatria,

Universidade Federal de São Paulo, São Paulo; Brazil.

ABSTRACT

BACKGROUND: It has been suggested that obsessive-compulsive disorder (OCD)

developing after clinically significant trauma may constitute an etiologically distinct

subtype of OCD. The objective of the present study was to investigate whether

patients who develop OCD after posttraumatic stress disorder [PTSD, i.e. “post-

traumatic OCD” (PsT-OCD)] display a distinctive neurocognitive pattern of

dysfunction, therefore supporting the validity of this OCD subtype. METHODS:

Patients with PsT-OCD (n = 16), “pre-traumatic” OCD [PrT-OCD (n = 18)], non-

traumatic OCD [NonT-OCD (n = 67)] and healthy controls (n=17) had their

performance compared on the following neuropsychological tests: the Wisconsin

Card Sorting Test (WCST), the Iowa Gambling Task (IGT), the Wechsler Memory

Scale Logical Memory (LM), the Brief Visual Memory Test-Revised (BVMT-R), and

the Wechsler Abbreviated Scale for Intelligence (WASI). RESULTS: We found that

patients with OCD, in general, were characterized by poor set-shifting abilities and

impaired verbal and visuospatial memories, findings that were independent from age,

education, severity of depressive symptoms and intellectual level. Further, impaired

set shifting abilities were found to correlate with the severity of obsessive-compulsive

symptoms in all groups of patients with OCD, with the exception of PsT-OCD.

Patients with PsT-OCD were characterized by impaired visuospatial recognition, a

dysfunction that was found to correlate with poor set-shifting abilities in this

particular group of patients, but not in individuals with other types of OCD or in

healthy controls. CONCLUSIONS: Although our study showed that PsT-OCD is

associated with a distinctive pattern of neurocognitive dysfunction, additional

research will be needed to clarify whether poor visuospatial recognition is a risk

factor, a correlate, or a consequence of obsessive-compulsive symptoms that develop

after severe traumatic events. KEY-WORDS: obsessive-compulsive disorder;

psychological trauma; psychopathology; memory.

INTRODUCTION

Obsessive-compulsive disorder (OCD) is characterized by unwanted and persistent

thoughts, images, or impulses (i.e. obsessions) and/or complex behaviors that include,

among others, repetitive hand washing, checking, and ordering (i.e. compulsions). In

order to meet current DSM-IV-TR diagnostic criteria for OCD, a patient has to

exhibit either obsessions and/or compulsions that result in marked anxiety or distress,

consume time (take more than 1 hour a day), or significantly interfere with the

person's normal routine, occupational (or academic) functioning, or usual social

activities or relationships (APA, 2000). In a recent review of studies that employed

the Composite International Diagnostic Instrument (Robins et al., 1988) as a

diagnostic instrument, the one-month prevalence of obsessive–compulsive disorder

(OCD) in the general population ranged from 0.3 in Brazil to 3.1% in US samples

(Fontenelle et al., 2006).

A number of correlates and potential risk factors associated with the development of

OCD have been identified through epidemiological studies (Fontenelle and Hasler,

2008), including demographic characteristics (such as age, gender, employment,

marital condition, education, race, and socioeconomic status), innate features (like

familial background), and environmental factors (such as pregnancy and birth

complications, substance abuse, and life events, including trauma).

The role of environmental factors, particularly life events and traumatic experiences,

in the pathogeneses of OCD is still a largely understudied field (Fontenelle and

Hasler, 2008). For example, in their two-stage epidemiological study, Valleni-Basile

et al. (1996) found that adolescents who had experienced more undesirable and less

desirable life events, as measured by the Coddington Life Events Scale for

Adolescents, were at higher risk for developing OCD later in life. Likewise, at least

three studies found a significant link between victimization and the development of

OCD in the general population (Jordan et al., 1991; Boudreaux et al., 1998, Maes et

al., 2000). For instance, experiencing a situation during which the person feared

serious injury or death was associated with increased rates of several psychiatric

disorders, including PTSD, major depressive episode, agoraphobia, social anxiety

disorder, and OCD (Boudreaux et al., 1998). More strikingly, while PTSD acted as a

strong mediator between victimization and most Axis I disorders, in one study rape

remained a significant and independent predictor of OCD (Boudreaux et al., 1998).

Although it had been suggested that traumatic events could shape the expression of

OCD (Gershuny et al., 2003; Sasson et al., 2005; Cromer et al., 2007a; Cromer et al.,

2007b), only lately has evidence concerning the validity of a specific post-traumatic

subtype of OCD emerged. In a recent study, patients who developed OCD after

traumatic events were compared to patients with non-trauma-related OCD and found

to be characterized by a latter age at onset of obsessions, higher prevalence of

obsessions with aggressive content; increased levels of “suicidality”, greater severity

of depression, anxiety, and aggression, symmetry, and miscellaneous obsessive-

compulsive symptoms; increased rates of mood, anxiety, impulse-control and tic

disorders, and a positive family history for PTSD, major depressive disorder, and

generalized anxiety disorder, but not for OCD (Fontenelle et al., 2008).

Based on these findings, we have proposed that OCD developing after a traumatic

event may constitute an etiologically distinct subtype of OCD, perhaps more related

to other mood and/or anxiety disorders than to endogenous OCD. Nevertheless, in

order to validate this incipient psychiatric phenotype, more studies investigating

whether “post-traumatic” OCD is also associated with particular neurocognitive

characteristics or different treatment outcomes are badly needed (Gershuny et al.,

2008). With this in mind, the objective of the present study was to investigate whether

OCD occurring simultaneously or after PTSD (herein termed PsT-OCD) is associated

with distinctive executive, memory, and intellectual patterns of dysfunction, therefore

adding greater validity to its existence. Since traumatic events have been shown to be

particularly detrimental to memory abilities (Golier and Yehuda, 2002; Bremner,

2006), we predicted that individuals with whose traumatic events/PTSD were

etiologically related to OCD (PsT-OCD) would be characterized by decreased

learning abilities when compared to individuals who experienced similar traumatic

events/PTSD after developing OCD, individuals with OCD without a history of

similar traumatic events//PTSD, and healthy controls.

METHODS

Subjects

The data set was composed of 101 consecutive outpatients with OCD diagnosis

according to the DSM-IV criteria. Patients were recruited from four different

university centers [UFRGS (n=35), UFBA (n=25), UFRJ (n=23), and UPE (n=18)],

each located in a different Brazilian city (including Porto Alegre, Salvador, Rio de

Janeiro and Recife, respectively) and interviewed between August 2003 and August

2008. Healthy controls were selected among the health and administrative staff of

University of São Paulo (n=17). All institutions belonged to the neuropsychology core

of the Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders

(CTOC), a collaborative enterprise of seven Brazilian centers aiming to investigate

characteristics of OCD patients and their families, spanning over all areas of OCD

research (Miguel et al., 2008).

To be included in the study, patients were required to have a DSM-IV diagnosis of

OCD confirmed by the Structured Clinical Interview for DSM-IV Axis I disorders

(SCID-I). Individuals suffering from with schizophrenia, dementia, or any other

condition that could limit their understanding of the procedures involved in the

research protocol were preliminarily excluded. The Institutional Review Board of

each institution involved in the CTOC approved this project. Accordingly, all

participants signed a written informed consent after a receiving a full description of

the study and the assurance that the decision not to participate in the project would not

interfere with their access to treatment. A complete account of the methodology of the

CTOC can be found elsewhere (Miguel et al., 2008).

Psychiatric Assessment

Research subjects were interviewed by psychologists or psychiatrists with experience

in the diagnosis and treatment of individuals with OCD. An array of standardized

instruments was applied: Structured Clinical Interview for Diagnosis of Axis I,

according to DSM-IV (SCID-I), Yale–Brown Obsessive–Compulsive Scale (Y-

BOCS), and Beck Depression (BDI) and Anxiety Inventories (BAI). Examiners from

different CTOC sites were intensively trained in two-day meetings three times a year

(2004-2006) in order to guarantee satisfactory reliability among participants, which

reached 96% (Miguel et al., 2008).

Neuropsychological Assessment

The C-TOC neuropsychological core selected a battery of neuropsychological tests

aimed at evaluating different aspects of cognitive performance, including executive

function, memory, and intellectual abilities. The evaluation of executive functioning

included the administration of the Wisconsin Card Sorting Test (WCST), an

instrument designed to assess, among other cognitive functions, set-shifting skills, an

ability presumably related to dorsal aspects of the prefrontal cortex, and the Iowa

Gambling Task (IGT), a test that is thought to tap decision-making biases and, as a

consequence, to probe the more ventral and medial aspects of the prefrontal cortex.

The battery for the assessment of memory comprised the Wechsler Memory Scale -R

Logical Memory (LM), a test that investigates verbal memory, and the Brief Visual

Memory Test-Revised (BVMT-R), to evaluate visuospatial memory abilities.

Intellectual skills were evaluated by means of the Wechsler Abbreviated Scale of

Intelligence (WASI).

The methods of administration and correction of the neuropsychological tasks were

standardized across the five CTOC sites. Examiners were re-trained and reassessed

three times a year. A PhD level neuropsychologist supervised the application of the

neuropsychological battery on each site. A detailed description of each of these tasks

is given below.

Executive function tests

Wisconsin Card Sorting Test (WCST)

We employed the computerized version of the WCST (Heaton et al., 1993). In this

test, subjects sit in front of a monitor exhibiting four stimulus cards with symbols that

differ in color, form, and number and are instructed to match each card of a series of

128 cards to one of the stimulus cards according to a specific criterion (color, form, or

number). Subjects are not informed of the matching criterion, but were told after each

trial whether the match was correct or not. The criterion changes automatically after

10 consecutive correct matches. Perseveration consists in continuing to sort the cards

according to a previous rule, even after the computer’s negative feedback shows that

this rule has been changed. The number of categories completed is the number of

times an individual gave 10 consecutive correct responses.

Iowa Gambling Task (IGT)

We employed the computerized version of the Iowa Gambling Task (IGT) (Bechara

et al., 1994). In this test, subjects sit in front of a monitor exhibiting four decks of

cards (termed A, B, C and D), each containing 40 cards. They are asked to choose a

card from any of the four decks. The “disadvantageous” decks (A and B) result in

large short-term monetary gains but even larger long-term losses, whereas

“advantageous” decks (C and D) lead to small short-term monetary gains but even

smaller long-term losses. Thus, the disadvantageous decks appear, at first, to be the

best choice, at least with respect to the amount to be won. Individuals with

orbitofrontal lesions tend to choose an excessive number of cards from decks A and

Memory tests

WMS-R Logical Memory

Immediate and 30-minute delayed trials of the WMS-R LM were administered to test

verbal memory (Wechsler, 1987). Briefly, story A is read once to the subject, who

then orally provides any information recalled. Next, story B is read twice to the

examinee, with any recalled information provided after each reading. The examiner

records the number of free recall units and thematic units. After 30 minutes of other

testing, the subject is asked to provide any piece of information recalled from Story A

and then Story B. A standard cue is provided if the subject has no recollection of a

story. The recall scores are again recorded.

BVMT-Revised

The Brief Visual Memory Test-Revised (BVMT-R) is a test of visuospatial memory

(Benedict, 1997). It consists of three learning trials in which six abstract designs are

presented for 10 seconds. A learning score is calculated by summing all designs

recalled across the three encoding trials (maximum score=36). Recall is scored by the

accuracy and correct placement of each figure (maximum score=12). Delayed recall

of the designs takes place after a 25-minute delay. A recognition trial then followed,

where subjects had to recognize six core stimuli from 12 designs (maximum score=6).

Intellectual assessment

WASI

The Wechsler Abbreviated Scale for Intelligence (WASI, 1999) is a short test of adult

intelligence composed of four subtests: similarities (evaluating abstract verbal

reasoning), vocabulary (measuring the extent to which one has learned, been able to

comprehend, and give definitions of some words), block design (assessing spatial

perception, visual abstract processing and problem solving) and matrix reasoning (a

subtest that evaluates nonverbal abstract problem-solving skills).

Statistical Analyses

The OCD sample was divided into three groups based on the presence of comorbid

PTSD and its temporal relationship with OCD, i.e. “post-traumatic OCD” [PsT-OCD

(n = 16)], “pre-traumatic OCD” [PrT-OCD (n = 18)], non-traumatic OCD [NT-OCD

(n = 67)]. Demographic, clinical, and neuropsychological features of these three OCD

groups were compared to those of healthy controls (n=17) using χ2 test or Fisher’s

Exact Test for categorical variables and multivariate analysis of variance (MANOVA)

for continuous variables. When the overall MANOVAs were significant (p < 0.05),

post hoc pairwise comparisons were done using partitioned χ2 test for categorical

variables and Least Significant Difference (LSD) or Dunnett's tests (according to the

homogeneity of variance) for continuous variables.

Because we found, as expected, some significant demographic and

psychopathological differences between the groups, we employed a multiple analysis

of covariance (MANCOVA) with diagnostic group as the fixed factor,

neuropsychological tests as dependent variables, and the above-mentioned MANOVA

findings as covariates. Statistical tests were two-tailed, and p values < 0.05 were

considered significant. Corrections for multiple comparisons were not made to avoid

missing potential effects.

RESULTS

General description of the sample

We recruited a total of 118 participants who fulfilled the inclusion criteria: 101

patients with OCD and 17 healthy controls. Patients with OCD were predominantly

female (n=59; 58.4%) with a mean age of 35.4 (±13.2) years. Fifty-nine (59.6%)

participants were single, 29 (28.7%) were married, 7 (6.9%) lived together with a

partner, and 4 (4%) were divorced or separated. The volunteers with OCD had 13.0 ±

3.7 years of study and 83% of them belonged to classes B or C (A being the highest

and E, the lowest), according to Brazilian norms. They reported the onset of

obsessions and/or compulsions at age 13.8 ± 9.1 years. Their mean scores on the Y-

BOCS, BDI, and BAI were, respectively, 26.9±7.3 (severe obsessive-compulsive

symptoms), 16.5±11.2 (mild-moderate depression), and 17.0±12.7 (moderate

anxiety). In terms of comorbid disorders, 58.2% of the patients with OCD exhibited a

current major depressive episode, 26.5% had specific phobia, 24.5% had social

phobia, 17.8% had generalized anxiety disorder, and 11.2% presented panic disorder

with or without agoraphobia. Most patients were already under psychological and/or

pharmacological treatment. A description of the socio-demographic features of the

healthy controls can be found in Table 1.

Comparison between OCD groups and healthy controls

The clinical (PsT-OCD, PrT-OCD, and NT-OCD) and the healthy control groups had

their socio-demographic, clinical and neuropsychological characteristics compared to

one another as seen in Tables 1, 2, and 3, respectively.

Table 1: Comparison of socio-demographic features between the groups

PST-OCD

(N=16)

PRT-OCD

(N=18)

NT-TOC

(N=67)

CONTROLS

(N=17)

MANOVA’S

P-VALUE

Age (in yrs)

39.2

12.4

‡

41.2

12.3

¶¶ /

33.0

13.2

29.9

7.9

P=0.01

Gender

P=0.80

male

9 (56.3%)

11 (61.1%)

39 (58.2%)

12 (70.6%)

Male

7 (43.8%)

7 (38.9%)

28 (41.8%)

5 (29.4%)

Education (in yrs)

11.6

4.2

13.6

4.3

13.1

3.4

14.0

2.7

P=0.26

Marital status

P=0.25

Single

10 (62.5%)

8 (44.4%)

41 (63.1%)

13 (76.5%)

Married

(18.8%)

9 (50.0%)

17 (26.2%)

3 (17.6%)

Divorced or separated

2 (12.5%)

0 (0.0%)

2 (3.1%)

1 (5.9%)

Other

1 (6.3%)

1 (5.6%)

5 (7.7%)

0 (0.0%)

Socioeconomic levels

P=0.55

Class A

0 (0.0%)

2 (11.1%)

4 (6.5%)

5 (31.5%)

Class B

6 (42.9%)

(33.3%)

25 (40.3%)

7 (43.8%)

Class C

7 (50%)

9 (50.0%)

25 (40.3%)

4 (25.0%)

Class D or lower

1 (7.1%)

1 (5.6%)

8 (12.9%)

0 (0.0%)

Footnote: PsT-OCD vs. PrT-OCD: ✽

✽✽

✽ p ≤ 0.05, ✽✽

✽✽✽✽

✽✽ p ≤ 0.01, ✽✽✽

✽✽✽✽✽✽

✽✽✽ p ≤ 0.001

PsT-OCD vs. NT-TOC: †

††

† p ≤ 0.05, ††

††††

†† p ≤ 0.01, †††

††††††

††† p ≤ 0.001

PsT-OCD vs. Controls: ‡

‡‡

‡ p ≤ 0.05, ‡‡

‡‡‡‡

‡‡ p ≤ 0.01, ‡‡‡

‡‡‡‡‡‡

‡‡‡ p ≤ 0.001

PrT-OCD vs. NT-TOC: §

§§

§ p ≤ 0.05, §§

§§§§

§§ p ≤ 0.01, §§§

§§§§§§

§§§ p ≤ 0.001

PrT-OCD vs. Controls: ¶ p ≤ 0.05, ¶¶ p ≤ 0.01, ¶¶¶ p ≤ 0.001

NT-TOC vs. Controls: ∆ p ≤ 0.05, ∆∆ p ≤ 0.01, ∆∆∆ p ≤ 0.001

Table 2: Comparison of psychiatric features between the groups

PST-OCD

(N=16)

PRT-OCD

(N=18)

NT-TOC

(N=67)

CONTROLS

(N=17)

MANOVA’S

P-VALUE

Severity of symptoms

BDI

23.8

10.8

†††‡‡‡

22.5

10.5

§§§

¶¶¶

13.1

9.5

∆∆∆

2.9

4.0

P<0.00

BAI

25.6

17.0

†††‡‡‡

23.6

11.8

§§§

¶¶¶

13.1

9.3

∆∆

2.9

3.7

P<0.001

YBOCS

Obsessions

12.2

5.0

‡‡‡

13.2

3.3

¶¶¶

13.4

3.4

∆∆∆

1.3

2.9

P<0.001

Compulsions

12.4

4.9

‡‡‡

13.4

3.5

¶¶¶

13.7

3.7

∆∆∆

1.8

3.2

P<0.001

Total

24.6

9.3

‡‡‡

26.6

6.4

¶¶¶

27.2

6.7

∆∆∆

3.2

5.9

P<0.001

Comorbidity

MDD

11 (68.8%)

‡‡

11 (61.1%)

¶¶

35 (54.7%)

∆∆

3 (18.8%)

P=0.02

Dysthymic disorder

1 (6.3%)

1 (5.6%)

4 (6.3%)

0 (0.0%)

P=0.60

Panic disorder

6 (37.5%)

✽†††‡‡‡

3 (16.7%)

2 (3.1%)

0 (0.0%)

P=0.00

Social phobia

5 (31.3%)

4 (22.2%)

15 (23.4%)

1 (6.3%)

P=0.28

Specific phobia

6 (37.5%)

‡

4 (22.2%)

16 (25.0%)

0 (0.0%)

P=0.01

GAD

5(31.3%)

2 (11.1%)

11 (17.2%)

1 (6.3%)

P=0.25

Substance abuse

2 (12.5%)

1 (5.6%)

2 (3.1%)

0 (0.0%)

P=0.32

Footnote: PsT-OCD vs. PrT-OCD: ✽

✽✽

✽ p ≤ 0.05, ✽✽

✽✽✽✽

✽✽ p ≤ 0.01, ✽✽✽

✽✽✽✽✽✽

✽✽✽ p ≤ 0.001

PsT-OCD vs. NT-TOC: †

††

† p ≤ 0.05, ††

††††

†† p ≤ 0.01, †††

††††††

††† p ≤ 0.001

PsT-OCD vs. Controls: ‡

‡‡

‡ p ≤ 0.05, ‡‡

‡‡‡‡

‡‡ p ≤ 0.01, ‡‡‡

‡‡‡‡‡‡

‡‡‡ p ≤ 0.001

PrT-OCD vs. NT-TOC: §

§§

§ p ≤ 0.05, §§

§§§§

§§ p ≤ 0.01, §§§

§§§§§§

§§§ p ≤ 0.001

PrT-OCD vs. Controls: ¶ p ≤ 0.05, ¶¶ p ≤ 0.01, ¶¶¶ p ≤ 0.001

NT-TOC vs. Controls: ∆ p ≤ 0.05, ∆∆ p ≤ 0.01, ∆∆∆ p ≤ 0.001

Table 3: Comparison of neuropsychological performance between the groups

PST-OCD

(N=16)

PRT-OCD

(N=18)

NT-TOC

(N=67)

CONTROLS

(N=17)

MANOVA’S P-

VALUE

Intelligence

Verbal IQ

85.8

16.8

‡‡

88.0

16.1

93.0

14.2

101.1

12.2

P=0.01

Visuospatial IQ

87.7

16.6

‡‡

91.6

18.3

95.0

16.2

103.4

13.8

P=0.04

Total IQ

87.3

15.8

‡‡

88.6

16.5

¶¶

93.5

14.5

102.8

12.9

P=0.01

WCST

Categor

ies completed

4.2

1.5

3.7

1.9

4.2

1.9

3.6

1.2

P=0.51

Inability to maintain set

1.6

1.9

1.3

1.2

2.3

0.4

0.9

P=0.34

Learning to learn

0.1

10.2

2.1

10.1

0.6

9.1

4.2

9.2

P=0.37

Perseverative errors

19.0

7.0

‡‡‡

21.9

10.7

¶¶¶

17.5

8.5

∆∆∆

4.5

6.2

P<0.001

Non

perseverative erros

22.1

12.5

22.1

11.2

24.4

19.9

15.7

8.3

P=0.29

IGT

Decks A+B

50.2

8.1

51.3

6.4

52.1

11.8

53.3

9.5

P=0.84

Decks C+D

49.9

8.1

48.7

6.4

48.4

11.9

46.7

9.5

P=0.85

Net score (C+D)

(A+B)

1.6

16.2

5.13

12.1

4.4

23.6

6.8

19.0

P=0.91

Logical Memory A

Immediate recall

11.2

3.7

10.8

4.3

11.6

4.1

13.9

3.6

P=0.10

Late recall

9.0

3.5

9.0

3.5

9.1

4.1

10.7

3.9

P=0.49

Logical Memory B

Immediate recall

8.5

3.4

‡‡‡

8.7

4.4

¶¶¶

10.2

3.8

∆∆

13.1

3.2

P=0.002

Late recall

6.5

4.0

‡‡‡

6.5

3.9

¶¶¶

8.0

3.6

∆∆

10.9

3.1

P=0.002

BVMT-R

Total recall

19.1

8.6

†‡‡‡

18.2

7.9

¶¶¶

23.0

7.5

∆

28.1

6.3

P=0.001

Delayed recall

7.6

3.3

†‡‡

7.9

3.1

¶¶

9.1

2.8

∆

10.8

1.6

P=0.006

Recognition

hits

5.1±1.0

✽✽†††‡‡‡

5.6

0.5

5.8

0.4

5.8

.0.4

P=0.003

Footnote: PsT-OCD vs. PrT-OCD: ✽

✽✽

✽ p ≤ 0.05, ✽✽

✽✽✽✽

✽✽ p ≤ 0.01, ✽✽✽

✽✽✽✽✽✽

✽✽✽ p ≤ 0.001

PsT-OCD vs. NT-TOC: †

††

† p ≤ 0.05, ††

††††

†† p ≤ 0.01, †††

††††††

††† p ≤ 0.001

PsT-OCD vs. Controls: ‡

‡‡

‡ p ≤ 0.05, ‡‡

‡‡‡‡

‡‡ p ≤ 0.01, ‡‡‡

‡‡‡‡‡‡

‡‡‡ p ≤ 0.001

PrT-OCD vs. NT-TOC: §

§§

§ p ≤ 0.05, §§

§§§§

§§ p ≤ 0.01, §§§

§§§§§§

§§§ p ≤ 0.001

PrT-OCD vs. Controls: ¶ p ≤ 0.05, ¶¶ p ≤ 0.01, ¶¶¶ p ≤ 0.001

NT-TOC vs. Controls: ∆ p ≤ 0.05, ∆∆ p ≤ 0.01, ∆∆∆ p ≤ 0.00

100

Because there were some significant differences between the groups, spanning current

age, severity of symptoms, patterns of comorbidity, and intelligence levels (tables 1,

2, and 3), comparisons were made using multiple analysis of covariance

(MANCOVA) with the diagnostic group as the fixed factor, neuropsychological tests

as dependent variables, and age at presentation, Beck’s anxiety and depression scores,

presence of major depression, panic disorder, specific phobia, and IQ scores as

covariates. As seen in table 4, only age of presentation reached a level of significance

that allowed it to be kept in the MANCOVA model.

Although controlling for age attenuated some of the findings described in the previous

model, most differences remained significant (Table 5). In our final MANCOVA

model, while patients with PsT-OCD, PrT-OCD and NT-OCD exhibited more

perseverative errors and verbal and visuospatial memory problems than healthy

controls, individuals with PsT-OCD and PrT-OCD seemed to be particularly impaired

from the cognitive point of view. Of note, patients with PsT-OCD exhibited less

recognition hits than patients with PrT-OCD.

101

Table 4: Multivariate analysis of variance of features that differed between groups

WILKS’ LAMBDA F DF P

Age 0.72 1.91 17 0.03

BDI 0.85 0.87 17 0.60

BAI 0.89 0.59 17 0.89

Major depressive disorder 0.84 0.89 17 0.58

Panic disorder 0.85 0.88 17 0.59

Specific phobia 0.85 0.83 17 0.65

Verbal IQ 0.92 0.43 17 0.97

Visuospatial IQ 0.86 0.77 17 0.71

Total IQ 0.89 0.60 17 0.87

102

Table 5: Comparison of neuropsychological performance between the groups controlling for age at presentation

PST-OCD

(N=16)

PRT-OCD

(N=18)

NT-TOC

(N=67)

CONTROLS

(N=17)

MANCOVA’S P-VALUE

WCST

Categories completed

4.2

1.9

3.7

2.0

4.2

2.0

3.5

1.2

P=0.53

Inability to

maintain set

1.8

2.3

1.3

1.1

2.6

0.8

P=0.40

Learning to learn

0.1

13.2

2.6

11.5

0.9

10.4

4.7

9.7

P=0.30

Perseverative errors

19.9

8.4

‡‡‡

22.5

11.2

¶¶¶

17.6

9.0

∆∆∆

1.8

2.1

P<0.001

Non

perseverative errors

21.9

15.4

22.0

11.9

24.7

2.12

14.7

8.4

P=0.30

IGT

Decks A+B

49.1

10.3

51.2

7.3

52.2

15.7

53.6

10.5

P=0.85

Decks C+D

50.9

10.3

48.8

7.3

48.4

15.9

46.3

10.5

P=0.87

Net score (C+D)

(A+B)

0.2

0.7

5.29

13.8

4.3

31.4

7.3

21.0

P=0.92

Logical Memory A

Immediate recall

11.1

4.0

‡

10.7

4.5

11.6

4.1

∆

13.9

3.5

P=0.11

Late recall

9.0

3.8

9.0

3.7

9.1

4.2

10.7

3.8

P=0.51

Logical Memory B

Immediate recall

8.3

3.6

‡‡‡

8.6

4.7

¶¶

3.8

∆∆

13.1

3.2

P=0.002

Late recall

6.3

4.2

‡‡‡

6.4

4.2

¶¶¶

8.0

3.6

∆∆

10.8

3.1

P=0.002

BVMT-R

Total recall

18.1

9.8

‡‡

17.4

8.4

¶¶

23.0

7.9

∆

28.0

6.3

P=0.001

Delayed recall

7.2

3.7

‡‡

7.7

3.4

9.1

2.9

∆

10.7

1.6

P=0.006

Recognition

hits

5.0±1.2

✽†††‡‡‡

5.6

0.5

5.7

0.4

5.7

0.4

P=0.001

Footnote: PsT-OCD vs. PrT-OCD: ✽

✽✽

✽ p ≤ 0.05, ✽✽

✽✽✽✽

✽✽ p ≤ 0.01, ✽✽✽

✽✽✽✽✽✽

✽✽✽ p ≤ 0.001

PsT-OCD vs. NT-TOC: †

††

† p ≤ 0.05, ††

††††

†† p ≤ 0.01, †††

††††††

††† p ≤ 0.001

PsT-OCD vs. Controls: ‡

‡‡

‡ p ≤ 0.05, ‡‡

‡‡‡‡

‡‡ p ≤ 0.01, ‡‡‡

‡‡‡‡‡‡

‡‡‡ p ≤ 0.001

PrT-OCD vs. NT-TOC: §

§§

§ p ≤ 0.05, §§

§§§§

§§ p ≤ 0.01, §§§

§§§§§§

§§§ p ≤ 0.001

PrT-OCD vs. Controls: ¶ p ≤ 0.05, ¶¶ p ≤ 0.01, ¶¶¶ p ≤ 0.001

NT-TOC vs. Controls: ∆ p ≤ 0.05, ∆∆ p ≤ 0.01, ∆∆∆ p ≤ 0.001

103

Further, we also found that BVMT recognition hits correlated significantly both with

WCST categories completed (rho=0.72; p=0.001) and perseverative responses (rho=0.61;

p=0.01) in patients with PsT-OCD, but not in healthy controls (rho=0.15; p=0.57 and rho=-

0.21; p=0.40, respectively), NT-OCD (rho=0.16; p=0.19 and rho=0.01; p=0.89,

respectively), and PrT-OCD (rho=2.9; p=0.28 and rho=-0.16; p=0.57, respectively).

The severity of obsessive-compulsive symptoms (Y-BOCS obsessions, compulsions, and

total scores) correlated significantly with WCST perseverative responses in patients with

NT-OCD (rho=0.47; p=<0.001, rho=0.47; p<0.001, and rho=0.50; p<0.001, respectively)

and PrT-OCD (rho=0.45; p=<0.05, rho=0.58; p=0.01, and rho=0.56; p=0.01, respectively),

but not in PsT-OCD (rho=0.26; p=0.35; rho=0.11; p=0.71, and rho=0.20;p=0.49,

respectively).

Discussion

We found that patients with OCD were characterized by poor set-shifting abilities and

impaired verbal and visuospatial memory even after controlling for age, education,

intellectual level and severity of depressive symptoms. Further, impaired set shifting

abilities were found to correlate with the severity of obsessive-compulsive symptoms in all

groups of patients with OCD, with the exception of PsT-OCD. Also, patients who

developed OCD after PTSD were distinctively characterized by impaired visuospatial

recognition, a dysfunction that was found to correlate with poor set-shifting abilities in this

particular group of patients, but not in individuals with other types of OCD or in healthy

controls.

In our study, all OCD samples exhibited higher average perserverative errors than the

healthy control group, a result that could not ascribed to differences in terms of age,

104

education, intellectual level and severity of depressive symptoms. Also, the severity of

obsessive-compulsive symptoms (i.e. obsessions, compulsions, and total scores) correlated

significantly with perseverative responses in the WCST in the NonT-OCD and the PrT-

OCD (but non in PsT-OCD). Nevertheless, whether patients with OCD exhibit increased

perseverative errors/responses in the WCST is area still opened to debate. For example,

while some studies have suggested that associated depression (Basso et al., 2001; Mataix-

cols et al., 2003), schizotypal symptoms (Aycicegi et al., 2003; Shin et al., 2008), or

intellectual impairment (Henry, 2006) are responsible for this association, other

investigations, like ours, support the idea that patients with OCD display a primary deficit

of set-shifiting ability that is independent of other confounding factors. As it was

previously proposed, although poor WCST performance may be worsened by a number of

confounding factors, it may also be negatively influenced by certain clinical features (e.g.

symmetry/ordering symptoms; Lawrence et al., 2006) or genetic polimorphisms (DA-48G,

DSer9Gly, 5-HTT102C and 5-HTT267C, Lane et al., 2008) that may be present in

individuals with OCD free from different comorbidities.

We found that all groups of patients with OCD exhibited a reduction in immediate and

delayed verbal episodic memory for short prose passages (LM from the WMS-R) in

comparison with healthy controls. These findings remained significant after controlling for

the effects of age, education, depression, or intellectual levels and had been already

reported in sub-clinical checkers (Sher et al., 1983) and in other samples of patients with

OCD (Roth et al., 2005; Exner et al., 2009). Of note, severity of obsessive-compulsive

symptoms correlated with impairment in logical memory, particularly in patients with

NonT-OCD. Recently, however, Andrés and coworkers argued that, at least in children

105

with OCD, impaired delayed recall might be ascribable to comorbid depression (Andrés et

al., 2007) and resistant to treatment (Andrés et al., 2008). Therefore, if left untreated, it is

possible that episodic memory impairment of children with OCD might consolidate later in

life independently of depression.

Traditionally, verbal memory impairment in patients with OCD has been assessed on the

basis of list-learning (CVLT or others) or paired associates paradigms (Cutler and Graf,

2009). Nevertheless, the recall of orally presented stories, such as employed in our study,

has been shown to predict every day memory problems in a wide range of clinical

conditions (Lezak, 1995). The inability of patients with OCD to memorize complex verbal

information may be related to their reduced capacity for semantic processing (Cabrera et

al., 2001; Deckersbach et al., 2000). As suggested by Exner et al. (2009a, 2009b), patients

with OCD might miss the overall semantic essence of the story while trying to keep track of

its every single detail.

On the other hand, patients with OCD, either trauma- or non-trauma-related, displayed

significantly reduced total and delayed recall of visuospatial information as compared to

healthy controls. As reported for set-shifting abilities and verbal memory functioning,

results for visuospatial memory could not be ascribed to differences in terms of age,

education, depression, or intellectual levels. Although not previously employed in OCD,

the BVMT results replicated visualspatial memory deficits seen in previous studies that

used the WAIS-R Visual Construction, the Benton Visual Retention, or the Rey Complex

Figure Test (Fontenelle et al., 2006). Further, the fact that all OCD groups, with the

exception of patients with PsT-OCD, exhibited preserved recognition hits suggests that

106

patients with “classical” OCD (PrT-OCD and NonT-OCD) display a typical fronto-striatal

retrieval deficit syndrome, instead of a simple impairment in the ability to store visuospatial

information (Cummings, 1993).

The existence of a post-traumatic subtype of OCD has been speculated for decades (van der

Kolk et al., 1989), though no previous study has attempted to delineate its differential

pathophysiology. In order to investigate the etiological role played by traumatic events in

certain cases of OCD, we focused our study in the neuropsychological functioning of

patients with PsT-OCD. As hypothesized, patients with PsT-OCD were found to be

distinctively impaired, i.e. they were characterized by significantly lower visuospatial

recognition hits than healthy controls, NonT-OCD and, more importantly, PrT-OCD (Table

5). Indeed, the comparison between PsT-OCD and PrT-OCD allowed us to control for the

impact of PTSD in brain functioning, i.e. lower visual recognition could not be ascribed to

the presence of PTSD in general but to PTSD occurring before OCD. Whether lower visual

recognition is a risk factor, a correlate, or a consequence of PsT-OCD, however, is not

possible to answer with a cross-sectional study such as ours.

Further, we also found that BVMT recognition hits correlated significantly both with

WCST categories completed and perseverative responses in patients with PsT-OCD, but

not in healthy controls, non-trauma related OCD and PrT-OCD. Taken together, these

findings probably suggest that PsT-OCD may be related to greater right hippocampal

dysfunction and, secondarily, to the impaired set-shifting abilities that are thought to

underlie obsessive-compulsive symptoms. These results are similar to those reported in

individuals with PTSD, who exhibited impaired verbal memory (Golier and Yehuda et al.,

107

2002; Johnsen and Asbjørnsen, 2009) and left hippocampal dysfunction (Villarreal et al.,

2002; Yehuda et al., 1999; Siegmund et al., 2009) in several studies. In other words, while

left hippocampal dysfunction could confer greater susceptibility to PTSD, right

hippocampal dysfunction may be a marker for the development of obsessive-compulsive

symptoms in the aftermath of PTSD.

Our study has several limitations that need to be taken into account. First, the number of

patients with pre- and post-traumatic OCD was relatively small. Clearly, a larger sample

would contribute greatly to elucidate the relationship between neuropsychological deficits

and different clinical groups. Nevertheless, one should consider that we are dealing with an

atypical, probably rare, OCD phenotype. Indeed, we have made the best of our efforts to

identify the greatest possible number of patients with PTSD-related OCD, a strategy that

was only possible in the context of a multicenter study conducted by a research consortium

such as ours.

Second, the fact that our study involved different research groups may raise questions

regarding the reliability of the methods of evaluation of cognitive abilities employed by our

neuropsychologists. In fact, although we did not test inter-rater reliability of

neuropsychological assessments formally, we tried to circumvent this potential limitation

by adopting strict instructions, routine calibration meetings, and regular supervision by an

expert neuropsychologist who would visit each center to check for data quality.

Third, since we have reported data on the neuropsychology of a clinical sample of patients

with OCD, most of our research subjects were under pharmacotherapy, including serotonin

108

reuptake inhibitors (as the main therapeutic anchors), atypical antipsychotics and, in cases

of treatment resistance or comorbid disorders, benzodiazepines (especially clonazepam). It

must be underlined, though, that traditional anti-OCD treatment did not seem to affect

neuropsychological performance in other OCD adult samples (Mataix-Cols et al., 2002).

Nevertheless, despite these reassuring results, we acknowledge that future studies on the

neuropsychology of PsT-OCD should investigate non-clinical samples or drug naïve

patients.

Finally, we did not employ any instrument to assess for the severity of PTSD symptoms. It

has already been demonstrated that severity of PTSD has a negative impact on measures of

cognitive performance, mainly memory tasks (Dickie et al., 2008). Therefore, we cannot

exclude the possibility that the lower number of recognition hits obtained by PsT-OCD

patients might reflect, perhaps, more severe PTSD symptoms.

In sum, we found that patients with OCD in general were characterized by impaired set-

shifting abilities, verbal and visuospatial memory that were independent from age,

education, depression and intellectual levels. Further, impaired set shifting abilities were

found to correlate with the severity of obsessive-compulsive symptoms in all groups of

patients with OCD. Patients who developed OCD after PTSD were distinctively

characterized by impaired visuospatial recognition, a dysfunction that was found to

correlate with poor set-shifting abilities in this particular group of patients.

109

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3) Discussão da tese

O TOC tem sido investigado a partir de diferentes perspectivas, i.e. classes de

sintomas, neuropsicologia, resposta ao tratamento (farmacológico, psicoterápico e

neurocirúrgico), neuroimagem, dentre outras – com o intuito de maximizar o conhecimento

acerca de suas características, sintomas e prognósticos para, assim, fornecer melhor

qualidade de vida aos que dele sofrem. Nesse mesmo caminho, têm sido realizadas

pesquisas com o Transtorno de Estresse Pós-Traumático (TEPT), uma vez que a

contemporaneidade traz consigo o aumento da violência e o consequente impacto que esta

pode causar sobre os seres humanos.

O que diferencia um indivíduo que desenvolve TOC ou TEPT, de outro que passou

pelas mesmas circunstâncias e nada sofreu? Que fatores fornecem esta capacidade de

resiliência? A ciência e suas inúmeras pesquisas buscam incansavelmente conhecer o ser

humano e dele extrair conhecimentos capazes de “prever” como cada um reagirá a

determinada situação. Assim, pode se observar o crescente interesse pelo impacto do

trauma nos pacientes que já têm ou que desenvolveram o TOC a partir deste evento.

Os pesquisadores têm se dedicado a estudar o papel do trauma no TOC tanto em

termos de características clínicas quanto de resposta ao tratamento. Muitos estudos

(Gershuny et al., 2003; Sasson et al., 2005; Cromer et al., 2007) verificaram que este grupo

de pacientes “TOC pós-traumáticos” apresentam diferenças quanto à resposta ao

tratamento, sendo mais resistentes às intervenções, principalmente psicoterápicas, o que

diverge do observado nos pacientes com TOC “puro”, que apresentam boa resposta ao

tratamento com a terapia cognitivo-comportamental, principalmente, frente à técnica de

Exposição e Prevenção de Respostas (EPR).

Os pacientes “TOC pós-traumáticos” também se apresentam clinicamente de forma

peculiar, ocorrendo o que os autores acima citados chamam de “conexão dinâmica” entre os

sintomas: quando os sintomas obsessivo-compulsivos melhoram (em freqüência e

intensidade), os traumáticos pioram (também em freqüência e intensidade). Tal padrão

“dinâmico” de sintomas não é observado, por exemplo, nos pacientes que apresentam

depressão comórbida com o TOC, quando se verifica melhora ou piora dos sintomas

depressivos e obsessivo-compulsivos simultaneamente. Além disso, muitos autores têm

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validado este grupo de pacientes como um subtipo específico de pacientes com TOC.

Fontenelle et al (2008) verificaram que os pacientes com “TOC pós-traumático” são

caracterizados por idade de início mais tardio das obsessões, maior prevalência de

obsessões de conteúdo agressivo, maiores níveis de “suicidabilidade”, maior severidade dos

sintomas depressivos, ansiosos e obsessivo-compulsivos, relacionados a determinadas

classes de sintomas (agressão, simetria e diversas).

Foi observada também, nesse grupo de pacientes, maior incidência de transtornos de

humor, ansiedade, de controle de impulsos e de tiques, além de história familiar positiva

para Transtorno de Estresse Pós-Traumático (TEPT), Episódio Depressivo Maior (EDM) e

Transtorno de Ansiedade Generalizada (TAG). Estes achados de história familiar chamam

atenção pois, no TOC “puro”, geralmente a história familiar para este transtorno é positiva.

Apesar de a literatura científica apontar para um possível papel etiológico em

comum para o desenvolvimento tanto do Transtorno Obsessivo-Compulsivo (TOC) quanto

do Transtorno de Estresse Pós-Traumático (TEPT), não foram encontrados estudos sob o

ponto de vista neuropsicológico que ajudassem a delimitar as semelhanças e diferenças

neste grupo de pacientes (“TOC pós-traumático”), comparado com os grupos de pacientes

com TOC ou TEPT “puros”. O presente estudo foi conduzido, então, com este objetivo,

sendo composto por uma amostra de civis, o que na literatura tem sido apontado como uma

vantagem nos estudos sobre trauma e TEPT.

Estudos vêm demonstrando disfunções executivas e déficits na memória não-verbal

de maneira bastante consistente nos pacientes com TOC “puro” ou primário, indicando que

estas características seriam “marcadores” destes pacientes (Rao et al, 2008). Em nosso

estudo, também foi verificado este “padrão” cognitivo típico nos grupos de pacientes com

TOC (TOC pós-traumático, TOC pré-traumático e TOC não-traumático) realmente tiveram

pior desempenho em tarefa de flexibilidade cognitiva (Wisconsin Card Sorting Test -

WCST), apresentando maior número de erros perseverativos nesta tarefa, comparados ao

grupo controle. Este desempenho pode refletir uma dificuldade na mudança do cenário

cognitivo, função relacionada ao córtex pré-frontal, mais dependente das regiões dorso e

ventro-lateral, que de regiões orbitais. Esta disfunção pode se refletir na natureza repetitiva

dos comportamentos e sintomas obsessivo-compulsivos (Menzies et al 2008).

115

Apesar de alguns estudos sugerirem o TOC como um transtorno caracterizado pela

dificuldade em tomar decisões (Sachdev and Malhi, 2005) – disfunção mais orbitofrontal -,

em nosso estudo todos os grupos se desempenharam de maneira bastante semelhante no

Iowa Gambling Task (IGT), o que não nos possibilita sugerir esta hipótese anterior de

dificuldade na tomada de decisões como verdadeira. Os pacientes com TOC (nos três

grupos estudados: TOC pós-traumático, TOC pré-traumático e TOC “não-traumático”)

demonstraram um pior desempenho que os controles saudáveis nas tarefas de memória,

tanto com material não-verbal quanto auditivo-verbal. Entretanto ,o grupo “pós-

traumático”, qualitativamente, obteve pior desempenho em alguns dos índices estudados

(Memória lógica B – recuperações imediata e tardia - e Brief Visual Memory Test-Revised

(BVMT-R) – resgate tardio e reconhecimento), sendo o reconhecimento de material não-

verbal ainda mais deficitário e com diferença estatisticamente significativa, quando

comparado aos demais grupos.

Estes resultados corroboram estudos anteriores que sugerem a presença de

dificuldades mnêmicas tanto nos pacientes com TOC (Savage et al., 1999, 2000;

Deckersbach et al., 2000) quanto nos pacientes com TEPT (Bremner et al., 2004;

Gilbertson et al., 2001). No que se refere à memória verbal, o teste utilizado (Memória

Lógica) é considerado como a medida de memória episódica mais “pura”, pois se

assemelha ao conteúdo cotidiano (Lezak et al, 2004). Em alguns estudos, o volume

hipocampal esquerdo se correlacionou ao desempenho no teste de Memória Lógica, tanto

no resgate imediato quanto no tardio.

Levando-se em consideração o achado estatisticamente mais significativo no nosso

artigo “Cognitive dysfunction in ‘post-traumatic’ obsessive-compulsive disorder” (Borges

et al, 2009), que se refere a dificuldades de reconhecimento de material não-verbal no

grupo “TOC pós-traumático”, tais resultados podem sugerir a presença de uma disfunção

hipocampal à direita. O reconhecimento é considerado por Lezak (2004) como

procedimento importante nas tarefas de memória não-verbal, quando o resgate livre é

deficitário, para tentar delimitar se as dificuldades observadas referem-se à aquisição ou à

retenção do material.

Em nosso estudo, a retenção parece mais comprometida que a aquisição no grupo

“TOC pós-traumático,” uma vez que a recuperação imediata (de material não-verbal) é até

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melhor que a do grupo “TOC pré-traumático” mas o resgate e o reconhecimento são mais

deficitários. O hipocampo tem sido identificado como local de interação entre a percepção

e os sistemas de memória, com papel importante na memória não-verbal. Lesões unilaterais

hipocampais trazem processos diferenciados: perda ou lesão de hipocampo esquerdo

implica em memória verbal comprometida, enquanto lesão hipocampal, à direita, resulta em

reconhecimento e resgate deficitários de materiais visual e auditivo complexos pouco

verbalizáveis (Lezak et al, 2004).

Esta autora também enfatiza a importância do hipocampo e de estruturas límbicas

no aprendizado de novas informações, enquanto o córtex temporal aparece como “moradia”

para informações já consolidadas. Lezak et al (2004) sugere que pacientes com lesões

frontais vão proporcionalmente melhor em tarefas de reconhecimento pois estas demandam

menor grau de organização da informação que no resgate livre. Para uma conclusão mais

definitiva referindo-se até que ponto tais déficits mnêmicos são conseqüência de disfunções

executivas primárias ou são manifestações “em si”, outros estudos precisam ser realizados,

pois existem achados consistentes para ambas hipóteses, como já citado anteriormente na

introdução desta tese.

Foi também verificado em nossos resultados que o grupo de pacientes “TOC pós-

traumáticos” apresentou menor QI e menor escolaridade, o que nos leva a uma reflexão

sobre o que é causa e conseqüência: tais pacientes apresentam menor grau de escolaridade

por apresentarem capacidade cognitiva mais baixa, ou o fato de apresentarem tais

comorbidades levou a uma maior evasão acadêmica, como conseqüência das limitações que

os transtornos psiquiátricos causam? Em um estudo anterior, menores escores de QI foram

sugeridos como sendo fatores de risco aumentados para o desenvolvimento do TEPT

(Macklin et al., 1998).

Estudos de neuroimagem estrutural e funcional sugeriram disfunções tanto em

córtex pré-frontal quanto temporal nos pacientes com TEPT (Kitayama et al., 2005; Shin et

al., 2001), indicando possíveis déficits executivos e mnêmicos. Em nosso estudo,

verificamos déficits mnêmicos (discutidos anteriormente) e dificuldades de mudança de

setting (maior índice de erros perseverativos), mas não de tomada de decisões (pela

performance no IGT). Indivíduos com TEPT parecem apresentar uma disfunção no

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circuito fronto-temporal, sugerindo a existência de um substrato neural anormal mediando

as funções executivas e mnêmica, tanto para estímulos traumáticos quanto para neutros.

Os estudos de neuroimagem que sugerem alterações tanto anatômicas quanto

funcionais do hipocampo, neste grupo de pacientes, corroboram nosso achado

neuropsicológico, entretanto não nos ajuda a definir se a alteração é anterior ao trauma ou

conseqüência dele (Caminha, 2005). A presença de TEPT fez com que tanto o grupo de

“TOC pós-traumático” quanto o “TOC pré-traumático” apresentassem pior desempenho em

todos os índices avaliados (exceto IGT), incluindo capacidade cognitiva global, testes de

memória verbal e não-verbal e um dos testes endereçados às funções executivas (WCST),

quando comparamos aos grupos de “TOC não-traumático” e controles. Ambos os grupos

com TEPT também apresentaram menor QI, menor escolaridade e maiores índices de

depressão e ansiedade, indicados pelos inventários de Beck utilizados (BDI e BAI).

Em relação ao tratamento deste grupo de pacientes, Wild et al (2008) verificaram

que o grau de dificuldade mnêmica diferenciava os pacientes que obtinham melhora com o

tratamento daqueles que não melhoravam (quanto maior o déficit mnêmico, menor a

melhora no tratamento). Levando-se em consideração o estudo de Graber et al (2008) cujos

achados sugerem que possivelmente os pacientes que possuem a comorbidade TEPT-TOC

procurem menos os serviços de tratamento especializados em programas de TOC,

preferindo tratar-se em ambulatórios de TEPT devido à maior predominância destes

sintomas, estudos futuros podem ajudar a planejar estratégias mais eficazes de tratamento

disponíveis tanto nos ambulatórios de TOC quanto de TEPT.

Por ter sido um estudo exploratório inicial, os resultados apresentados não podem

ser generalizados, pois apresentam suas limitações e precisam ser mais investigados,

pretendendo que este seja um estudo preliminar para que este grupo de pacientes (“TOC

pós-traumáticos”) receba formas de tratamento mais específicas e eficazes.

118

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6) Participação em outras Produções Científicas:

6.1) Artigo 1: Rev Bras Psiquiatr. 2008; 30 (3):185-96

ORIGINAL ARTICLE

The Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders:

recruitment, assessment instruments, methods for the development of multicenter

collaborative studies and preliminary results

Consórcio Brasileiro de Pesquisa em Transtornos do Espectro Obsessivo-Compulsivo:

recrutamento, instrumentos de avaliação, métodos para o desenvolvimento de estudos

colaborativos multicêntricos e resultados preliminares

Euripedes Constantino Miguel,

Ygor Arzeno Ferrão,

Maria Conceição do Rosário,

3,4

Maria Alice de Mathis,

Albina Rodrigues Torres,

Leonardo Franklin Fontenelle,

Ana Gabriela Hounie,

Roseli Gedanke Shavitt,

Aristides Volpato Cordioli,

Christina Hojaij Gonzalez,

Kátia Petribú,

Juliana Belo Diniz,

Dante Marino Malavazzi,

Ricardo C Torresan,

Andréa Litvin Raffin,

Elisabeth Meyer,

Daniela T Braga,

Sonia

Borcato,

Carolina Valério,

Luciana N Gropo,

Helena da Silva Prado,

Eduardo Alliende Perin,

Sandro Iêgo Santos,

Helen Copque,

Manuela Corrêa Borges,

Angélica Prazeres Lopes,

Elenita D da Silva,

The Brazilian Research Consortium on

Obsessive-Compulsive Spectrum Disorders (CTOC)*

Abstract

Objective: To describe the recruitment of patients, assessment instruments, implementation,

methods and preliminary results of The Brazilian Research Consortium on Obsessive-

Compulsive Spectrum Disorders, which includes seven university sites. Method: This

cross-sectional study included a comprehensive clinical assessment including semi-

structured interviews (sociodemographic data, medical and psychiatric history, disease

course and comorbid psychiatric diagnoses), and instruments to assess obsessive-

compulsive (Yale-Brown Obsessive-Compulsive Scale and Dimensional Yale-Brown

Obsessive-Compulsive Scale), depressive (Beck Depression Inventory) and anxious (Beck

Anxiety Inventory) symptoms, sensory phenomena (Universidade de São Paulo Sensory

Phenomena Scale), insight (Brown Assessment Beliefs Scale), tics (Yale Global Tics

Severity Scale) and quality of life (Medical Outcome Quality of Life Scale Short-form-36

and Social Assessment Scale). The raters’ training consisted of watching at least five

videotaped interviews and interviewing five patients with an expert researcher before

interviewing patients alone. The reliability between all leaders for the most important

instruments (Structured Clinical Interview for DSM-IV, Dimensional Yale-Brown

126

Obsessive-Compulsive Scale, Universidade de São Paulo Sensory Phenomena Scale) was

measured after six complete interviews. Results: Inter-rater reliability was 96%. By March

2008, 630 obsessive-compulsive disorder patients had been systematically evaluated. Mean

age (±SE) was 34.7 (±0.51), 56.3% were female, and 84.6% Caucasian. The most prevalent

obsessive compulsive symptom dimensions were symmetry and contamination. The most

common comorbidities were major depression, generalized anxiety and social anxiety

disorder. The most common DSM-IV impulsive control disorder was skin picking.

Conclusion: The sample was composed mainly by Caucasian individuals, unmarried, with

some kind of occupational activity, mean age of 35 years, onset of obsessive-compulsive

symptoms at 13 years of age, mild to moderate severity, mostly of symmetry,

contamination/ cleaning and comorbidity with depressive disorders. The Brazilian Research

Consortium on Obsessive-Compulsive Spectrum Disorders has established an important

network for standardized collaborative clinical research in obsessive-compulsive disorder

and may pave the way to similar projects aimed at integrating other research groups in

Brazil and throughout the world.

Descriptors: Obsessive-compulsive disorder; Clinical medicine; Multicenter study;

Diagnosis; Prevalence

127

Resumo

Objetivo: Descrever o recrutamento de pacientes, instrumentos de avaliação, métodos para

o desenvolvimento de estudos colaborativos multicêntricos e os resultados preliminares do

Consórcio Brasileiro de Pesquisa em Transtornos do Espectro Obsessivo-Compulsivo, que

inclui sete centros universitários. Método: Este estudo transversal incluiu entrevistas semi-

estruturadas (dados sociodemográficos, histórico médico e psiquiátrico, curso da doença e

diagnósticos psiquiátricos comórbidos) e instrumentos que avaliam os sintomas do

transtorno obsessivo-compulsivo (Escala para Sintomas Obsessivo-Compulsivos de Yale-

Brown e Escala Dimensional para Sintomas Obsessivo-Compulsivos de Yale-Brown),

sintomas depressivos (Inventário de Depressão de Beck), sintomas ansiosos (Inventário de

Ansiedade de Beck), fenômenos sensoriais (Escala de Fenômenos Sensoriais da

Universidade de São Paulo), juízo crítico (Escala de Avaliação de Crenças de Brown),

tiques (Escala de Gravidade Global de Tiques de Yale) e qualidade de vida (questionário

genérico de avaliação de qualidade de vida, Medical Outcome Quality of Life Scale Short-

form-36 e Escala de Avaliação Social). O treinamento dos avaliadores consistiu em assistir

cinco entrevistas filmadas e entrevistar cinco pacientes junto com um pesquisador mais

experiente, antes de entrevistar pacientes sozinhos. A confiabilidade entre todos os líderes

de grupo para os instrumentos mais importantes (Structured Clinical Interview for DSM-

IV, Dimensional Yale-Brown Obsessive-Compulsive Scale, Universidade de São Paulo

Sensory Phenomena Scale ) foi medida após seis entrevistas completas. Resultados: A

confiabilidade entre avaliadores foi de 96%. Até março de 2008, 630 pacientes com

transtorno obsessivo-compulsivo tinham sido sistematicamente avaliados. A média de

idade (±SE) foi de 34,7 (±0,51), 56,3% eram do sexo feminino e 84,6% caucasianos. Os

sintomas obsessivo-compulsivos mais prevalentes foram os de simetria e os de

contaminação. As comorbidades psiquiátricas mais comuns foram depressão maior,

ansiedade generalizada e transtorno de ansiedade social. O transtorno de controle de

impulsos mais comum foi escoriação neurótica. Conclusão: Este consórcio de pesquisa,

pioneiro no Brasil, permitiu delinear o perfil sociodemográfico, clínico e terapêutico do

paciente com transtorno obsessivo-compulsivo em uma grande amostra clínica de

pacientes. O Consórcio Brasileiro de Pesquisa em Transtornos do Espectro Obsessivo-

Compulsivo estabeleceu uma importante rede de colaboração de investigação clínica

padronizada sobre o transtorno obsessivo-compulsivo e pode abrir o caminho para projetos

semelhantes destinados a integrar outros grupos de pesquisa no Brasil e em todo o mundo.

Descritores: Transtorno obsessivo-compulsivo; Medicina clínica; Estudo multicêntrico;

Diagnóstico; Prevalência

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Introduction

Obsessive-compulsive disorder (OCD) is a common and disabling disorder.

Despite the

increasing number of studies investigating aspects of OCD clinical characteristics, genetics,

neuroimaging and treatment response, the pathogenesis of the disorder remains unknown,

and a substantial number of patients do not respond to available treatments.

2,3

One of the most frequent constraints that limit the progress of OCD research is the

relatively small number of patients enrolled in most studies, which contributes to reducing

the statistical power and to limiting interpretation of findings.

Therefore, patient recruitment and proper evaluation is a fundamental step for the

development of clinical research. However, this is not always an easy task. There are

patients who do not accept participating or do not look for treatment for reasons related to

intrinsic characteristics of the condition. These include features such as fear,

embarrassment, lack of insight, symptom severity and specific presentations of obsessive-

compulsive symptoms (OCS). All of them implicate in more limited access to patients.

Another challenge is to perform a comprehensive evaluation in a great number of patients.

Detailed phenotypic interviews are very time-consuming and need careful training of

several reliable interviewers to be administered to a substantial number of subjects.

One strategy to overcome these limitations and optimize recruitment and training efforts is

multicenter collaborations between research groups, also called consortiums. This type of

initiative, usually limited to a specific research area, has already been applied to several

psychiatric disorders, including schizophrenia

and bipolar disorders.

There are no

published studies using this type of approach in OCD.

The purpose of this study is to present initial findings of The Brazilian Research

Consortium on Obsessive-Compulsive Spectrum Disorders (CTOC), an enterprise of seven

Brazilian centers aiming to investigate characteristics of OCD patients and their families,

spanning over all areas of OCD research.

More precisely, this paper provides a detailed description of the CTOC implementation and

its methodology, including recruitment of patients, assessment instruments, quality

assurance procedures and the inter-rater reliability process. We also present the

demographic and clinical characteristics of the initial 630 patients evaluated.

Method

1. Ethical issues

CTOC research projects were submitted to and approved by the local Ethics Committees of

the involved centers (Process: USP-968/05; IPA-6600023; UFRGS-06/171; Unifesp-

302/2006 and UFRJ-0024.0.249.000-06). Written informed consents were obtained from all

participants, after a thorough description of the objectives and methods of each study, and

129

the reassurance that their decision to participate or not would not have any impact on their

treatment availability. When the subject was younger than 18 years old, a written informed

consent form was signed by the subject and also by a parent or legal guardian.

2. CTOC organization and structure

The CTOC was created in 2003. It has a self-governing organizational structure to facilitate

the establishment of group policies and procedures. There are sub-committees for different

issues, as shown in Figure 1.

a) Universidade de São Paulo (USP); b) Universidade Federal de São Paulo (Unifesp); c)

Universidade Estadual Paulista (Unesp); d) Universidade Federal do Rio de Janeiro

(UFRJ); e) Universidade Federal do Rio Grande do Sul and Universidade Metodista do Sul

- Instituto Porto Alegre (UFRGS-IPA); f) Universidade Federal de Pernanbuco (UFPE); g)

Universidade Federal da Bahia (UFBA). OCD - Transtorno Obsessivo-Compulsivo.

130

The main objectives of the CTOC are to systematically collect clinical data of OCD

patients from multiple centers, building a database for collaborative studies; to stimulate the

development of expert groups in this field throughout the country; to share information and

to set up a higher standard of care for Brazilian OCD patients; to promote research training

in this field; to create, translate, adapt and validate instruments to assess OCD; and to

generate new findings that can contribute to the understanding and treatment of OCD and

the most common psychiatric comorbidities.

Since 2006, the CTOC has been sponsored mainly by the National Council for Scientific

and Technological Development (CNPq, i.e., the Millennium Project), but also by grants

from Fundação de Amparo à Pesquisa do Estado de São Paulo (Fapesp).

A website was created to facilitate the communication between members

(http://protoc.incubadora.fapesp.br/portal/ctoc/). At this restricted website, assessment

instruments, videos for interview training and inter-rater reliability assessment, tasks,

workshop planning and other information are available online.

3. Description of each center

Brazil is a country with continental dimensions and great cultural diversity. It has 26 states,

divided into five regions, and a current population of almost 190 million inhabitants

(Brazilian Institute of Geography and Statistics – IBGE, 2008, available at http//:www.

ibge.org.br). Each region has its own culture, ethnic distribution, and socioeconomic

characteristics. In order to contemplate this diversity, the CTOC is composed of seven

centers from five Brazilian states and three different regions (Table 1).

131

This cross-sectional study is the result of the recruitment of the first three years (from 2005

to 2007). CTOC structure and principles allow each center to have independent research

projects in different fields, such as the phenotype dissection of OCD heterogeneity,

genetics, neuropsychology, neuroimaging and clinical trials with pharmacotherapy,

cognitive-behavioral therapy and neurosurgery for refractory cases. Each leading team may

invite researchers from other centers to participate as co-authors, so that several projects are

currently underway.

4. Implementation of the CTOC

The analyses of the variables originated from the instruments listed bellow will be planned

for each new research project, according to the specific characteristics and objectives of the

various studies to be conducted with this database. All future studies using the CTOC

dataset will be based on predefined hypotheses.

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1) Assessment instruments

Initially, the leaders from each center gathered in two different occasions to decide which

instruments should be included in the “Initial Evaluation Protocol” and to nominate

researchers for each of the sub-committees. The current version of the ”Initial Evaluation

Protocol” is an assessment package (available at http://protoc.

incubadora.fapesp.br/portal/ctoc/) that includes an informed consent form,

sociodemographic, socioeconomic (according to Associação Brasileira de Institutos de

Pesquisa de Mercado – ABIPEME -scale), medical history data, a semi-structured

interview about family psychiatric history (available under request), and the instruments

briefly described below. The research protocol is usually completed over the course of one

to three meetings (2 to 3 hours each), which are scheduled with intervals as short as

possible. Each center may add instruments to this basic research protocol, according to

approved specific projects.

2) Clinical assessment

Structured Clinical Interview for DSM-IV (SCID-I)6 and additional modules for tic and

impulse control disorders.

Attention deficit hyperactivity disorder (ADHD) and separation

anxiety disorder are investigated through a module of the Kiddie Schedule for Affective

Disorders and Schizophrenia (K-SADS).

Yale-Brown Obsessive-Compulsive Scale (Y-

BOCS).

This scale has been used worldwide to evaluate OCS severity. It has been

translated into Portuguese by Asbhar et al., 2002. Dimensional Yale-Brown Obsessive-

Compulsive Scale (DYBOCS).

It evaluates OCS according to specific dimensions, which

include obsessions and related compulsions. The severity of each dimension can be

independently quantified. Another advantage of this scale is that avoidant behaviors, mental

and repetitive rituals are investigated within each dimension, allowing for a more precise

evaluation of the severity of patients’ symptoms. It also investigates the time spent with

OCS, the level of anxiety and interference, with scores ranging from 0 to 5 (maximum of

15 for each dimension). The negative impact of OCS is also measured (maximum score of

30) and the therapeutic response can be evaluated according to specific dimensions. This

instrument was simultaneously validated in Portuguese and English.

Yale OCD Natural History Questionnaire (Leckman et al., 2002, unpublished manuscript,

translated into Portuguese by Rosário et al., 2002). This is a detailed instrument about OCS

onset and course, including several life events and situations that may contribute to trigger,

worsen or improve symptoms.

Yale Global Tic Severity Scale (YGTSS).

This scale has been used worldwide to evaluate

the nature and severity of motor and vocal tics. Translated into Portuguese by Miguel et al.,

2000. Beck Depression and Anxiety Inventories.

12,13

Translated into Portuguese by

Gorenstein and Andrade, 1996.

These are widely known scales to evaluate depressive and

anxiety symptoms. Universidade de São Paulo Sensory Phenomena Scale (USP-SPS).

The USP-SPS evaluates the presence and severity of sensory phenomena (SP - subjective

experiences of physical or mental sensations associated with repetitive behaviors). It is a

semi-structured scale composed by two parts. The first one investigates the occurrence of

past and current SP, divided into physical and mental sensations (examples of each type are

133

supplied), including age at onset. The second part measures the frequency, distress and

interference caused by each SP, in Likert scales ranging from 0 to 4 or 5.

Multimodality Treatment Assessment Study -Swanson, Nolan and Pelham Questionnaire

(SNAP – IV) for parents and teachers (translated into Portuguese by Mattos et al., 2006).

This scale evaluates symptoms of hyperactivity and attention deficit.

Brown Assessment of Beliefs Scale (BABS).

Translated into Portuguese by Ferrão and

Hounie, 2002. The BABS is a clinician-administered scale to evaluate different aspects of

the patient’s insight: conviction regarding the belief, perception of others’ views and

explanation of different views about it, fixity of belief, attempts to disprove it, whether the

individual recognizes a psychiatric/psychological cause for the belief, and presence of ideas

of reference.

Social Assessment Scale (SAS). Translated into Portuguese by Gorenstein et al., 2002.

This 42-item scale evaluates the quality of nine areas of participants’ social life: work

(three areas), leisure, family, marital status, offspring, domestic life and financial status.

Brazilian version of the Medical Outcomes Study Short Form 36 (SF-36). Translated and

validated to Portuguese by Ciconelli et al., 1999.

The SF-36 evaluates the quality of life

in the previous month and consists of 11 items, subdivided into 36 questions. It comprises

questions about physical, social and emotional health, regarding different activities and

general limitation.

Clinical Global Impressions Scale (CGI, adapted version).

The CGI investigates the

health professional’s impression regarding the patient’s problem severity.

5. Training of the Interviewers and CTOC meetings

In order to guarantee a standardized use of the instruments, experienced clinicians trained

the personnel from all the centers. A PhD level psychologist from Universidade de São

Paulo (USP) visited the other CTOC sites to conduct training sessions on the application of

structured interviews, which had already been used at USP. In addition, since 2003, two-

day meetings have been held three times a year to discuss, practice and standardize the

utilization of the research instruments (13 meetings so far).

Workshops on specific issues were also organized in order to present research results,

discuss new research projects and specific methodological aspects. Brazilian experts on

several areas (e.g. immunology, genetics, neuroimaging, neuropsychology,

psychopathology of other disorders, statistics, database, etc.) have been invited to improve

the discussions. During every CTOC meeting, a videotaped interview with a patient,

including the SCID-I, DY-BOCS and USP-SPS interviews, was watched by all

participants, who rated their evaluations using individual answer sheets that were inserted

in a specific database for reliability evaluations. Nine meetings with this aim have already

been organized so far. As this is an ongoing consortium project, live and videotaped

interviews will be continuously rated by participants for reliability purposes (at least twice

a year).

134

Interviews using the above cited instruments, conducted by experienced professionals, are

also available at the CTOC website, facilitating new members’ training. Training consists

of watching at least five videotaped interviews, observing five live interviews and

interviewing five patients with the supervision of another researcher before interviewing

patients alone. Instructions about the use of the most important instruments are also

available at the CTOC website, as well as the most frequent doubts and questions regarding

the use of these scales. In case of remaining questions about interviews, the Assessment

Instruments sub-committee can be consulted.

The leaders also promote continuous training in their centers to guarantee a high level of

reliability among the participants of the local research teams.

All research protocols are sent to the Central Data Core (USP) and are thoroughly reviewed

for quality assurance before insertion in the CTOC database. This is performed by a

psychologist (MAM) who has directly participated in the training of members from all

centers. She extensively checks all the files to detect possible missing or incongruent data.

When found, the protocol is returned to the original site for correction (if necessary, the

patient is reinterviewed). After insertion, the data are also reviewed by the Database

subcommittee, constituted by six members. Copies of the research protocols are stored

locally at each center. The final database is available for each center leader (Figure 1).

6. Types of studies

1) Phenotypical studies

These are the core projects conducted by the CTOC, since all centers use the “Initial

Evaluation Protocol” that has all the phenotypic information. Based on the clinical

assessment instruments, several studies on the phenotypical expression of OCD are being

conducted or being prepared, including gender differences, early vs. late onset of

symptoms, specific comorbidity patterns (e.g. patients with and without tic disorders,

substance use and impulse control disorders, and social anxiety disorder) and specific

clinical features of some symptom dimensions (e.g. hoarding obsessions and compulsions),

presence of suicidal thoughts, plans and attempts, etc.

2) Other studies

Performed by some of the centers, depending on their specificities, investigating the

following aspects: a) Genetic Studies (the CTOC is part of an international consortium for

genetic studies in OCD). Blood serum and DNA from blood or saliva are also obtained

from patients and first-degree relatives to perform molecular genetics and immunological

investigations); b) Neuroimaging studies, investigating cerebral structural and functional

alterations; c) Neuropsychological studies, investigating brain function as possible

endophenotypes; d) Clinical trials, investigating the response to pharmacological or

cognitive-behavioral approaches.

135

136

7. Sample recruitment

Until March 2008, a total of 630 patients had been systematically evaluated and included in

the dada set. Inclusion criteria: individuals under treatment in any of the seven sites, who

had DSM-IV OCD as their main psychiatric diagnosis confirmed by the SCID-I,

and were

able to understand and agreed to participate in the research protocol.

Forty-six patients from all centers were excluded from the study: seven patients fulfilled

DSM-IV diagnostic criteria for schizophrenia; one patient was unable to understand and

provide informed consent and 38 subjects refused to participate: 32 due to the long time

spent to answer all the research protocol, and six did not agree to sign the informed consent

(two were afraid of being identified, and four did not want to supply blood for genetic

research).

Sources of referral included outpatient (mostly) and inpatient clinics, clinicians in primary

or secondary health care units, private psychiatric services (150 from São Paulo and 20

from Rio Grande do Sul), websites, media advertisements, self-help groups and the

Brazilian Association of Obsessive-Compulsive and Tourette Syndrome Disorders

(ASTOC – www.astoc.org.br). Recruitment efforts were focused on individuals living in

the local area or patients presenting for treatment at the centers.

8. Statistical analyses

Initially, the frequency and distribution calculations of selected variables were performed

for the sample as a whole, using mean ± standard error (SE), percentages, median,

minimum and maximum values. For the differences between centers, Pearson’s chi-square

for categorical (dichotomic or polytomic) variables was used. Tests were adjusted for all

pairwise comparisons within a row of each innermost suitable using the Bonferroni

correction. One-way analysis of variance (ANOVA) followed by the post-hoc Scheffé test

(normal distribution) or Kruskal-Wallis H test (non-normal distribution) for continuous

variables were performed. Scales scores (e.g. Y-BOCS, DY-BOCS, BABS, BDI, BAI,

YGTSS) were analyzed as continuous variables.

The initial objective of this study was to measure the inter-rater reliability between the

leaders of all CTOC centers with at least six patients thoroughly evaluated. As it is an

ongoing consortium work, the reliability analyses will be continuously performed every ten

cases. At this moment, for an initial reliability evaluation, only the core instruments for

most studies and those that could lead to higher occurrence of disagreement between

evaluators were chosen. It must be highlighted that the inter-reliability was not assessed for

those scales that are very descriptive (straight forward answers) and less clinical, with little

room for disagreement. Furthermore, all participants watched the videos together and

discussed each of the differences.

The statistical level of significance adopted was 5%. The software used in all analyses was

the Statistical Package for Social Science (SPSS), version 15.0 (SPSS Inc., Chicago, USA).

137

Results

1. Inter-rater reliability

Concerning the reliability of instrument administration between raters, the leaders of each

center watched and independently rated at least six patients’ videotaped interviews of the

SCID-I, DY-BOCS and USP-SPS, totalizing 191 items, which were analyzed. The answers

could be dichotomic or ordinal. Of these 191 items, 184 (96%) were concordant by the

eight leaders of the research centers. Three items (1.6%) were discordant for one rater,

three items (1.6%) for two raters and one item (0.5%) for four raters.

2. Demographic and clinical data

Of the 630 patients, 308 (49.0%) came from USP, 126 (20.0%) from Universidade Federal

do Rio Grande do Sul-Universidade Metodista do Sul (UFRGS-IPA), 73 (11.6%) from

Universidade de Pernambuco (UPE), 49 (7.8%) from Universidade Estadual Paulista

(Unesp), 33 (5.2%) from Universidade Federal de São Paulo (Unifesp), 23 (3.7%) from

Universidade Federal da Bahia (UFBA), and 17(2.7%) from Universidade Federal do Rio

de Janeiro (UFRJ). Table 2 shows the main sociodemographic and clinical features for the

total sample and of each of the centers. Having no partner was more frequent at the UPE

center and the lowest rates of unemployment appeared at the UFRGS-IPA center. The

sample evinces a higher prevalence of social class A at the USP center (reflecting the

higher frequency of private patients in this center) and social class E at UFBA. Higher

mean educational level was found at USP (also secondary to the higher frequency of private

patients in this center). The age at onset of OCS was higher for the Unesp center, and the

longest time gap to start any kind of appropriate treatment occurred at UFRGS-IPA.

According to Y-BOCS, DY-BOCS and CGI, the most severe cases were presented by the

UFRGS-IPA and UPE centers.

Although it was not an initial purpose of this study, the sociodemographic and clinical

characteristics of patients from private and public services were compared, since it was

believed to be a potential confounding variable. The patients recruited from public services,

when compared to private ones, were more likely to be female, from lower social class, less

educated, and to present a longer time gap to start treatment. They also tended to be older

when they get the OCD diagnosis and to have more severe OCS (measured by the Y-BOCS

and DY-BOCS), as shown in Table 3.

138

139

Prior to the interview, the most frequently used anti-obsessive medications were fluoxetine

(n = 290, 46.0%); clomipramine (n = 220, 34.9%); paroxetine (n = 166, 26.3%), and

sertraline (n = 166, 26.3%). The most frequently used benzodiazepines were clonazepam (n

= 185, 29.4%), diazepam (n = 81, 12.9%), and alprazolam (n = 70, 11.1%), and the most

frequently used antipsychotics associated with the SSRIs were risperidone (n = 61, 9.7%),

haloperidol (n = 52, 8.3%), and olanzapine (n = 33, 5.2%).

According to the DY-BOCS, the most prevalent symptom dimension was symmetry. The

other dimensions are described in Figure 2. The most common “other OCS” were

obsessions of separation from parents or other relatives (n = 248; 39.4%), superstitious

obsessions (n = 226; 35.9%), obsessions about medical diseases (n = 203; 32.2%),

“slowness, repetitive behaviors” (n = 202; 32.1%), and compulsions to prevent from losing

a relative (n = 201; 31.9%). The DY-BOCS dimensions median scores were (25th

percentile-75th percentile): aggression – 4 (0-9); sexual-religious – 0 (0-8); symmetry,

order – 8 (3-11); contamination, cleaning – 7 (0-11); hoarding – 0 (0-6); other OCS – 8 (3-

11) and total score – 22 (18-25).

The lifetime psychiatric comorbidities are listed in Table 4. The five most common

comorbidities were major depressive disorder, generalized anxiety disorder, social anxiety

disorder (“social anxiety disorder” has been proposed as an alternative for the DSM-IV

established term “social phobia”), simple phobia and separation anxiety (investigated in all

sample, including adults). Among impulsive control disorders, skin picking appeared as the

most common comorbidity followed by compulsive buying, intermittent explosive disorder

and trichotillomania. Eating disorders were present in less than 10% of the sample, as well

as drug/alcohol abuse or dependence and ADHD.

The mean (±SE) age of the first tic was 12.87 (±0.62), ranging from 1 to 55 years old

(median = 12.0). The USP-SPS was administered to 605 subjects; 395 (65.3%) of them

presented any of the sensory phenomena and the total mean (±SE) score of the scale was

7.81 (±0.17), ranging from 1 to 15.

The mean (±SE) score of BDI of 613 patients was 15.54 (±0.45), ranging from 0 to 53

(median = 14); and of BAI was 15.15 (±0.46), ranging from 0 to 53 (median = 13.0).

Among the 593 patients that answered the BABS, the mean (±SE) score was 6.49 (± 0.22),

ranging from 0 to 24 (median = 6). The quality of life of 378 patients of the sample

(60.0%), according to the SF-36, showed the following scores [mean(±SE)]: functional

capacity: 83.79 (±1.04); limitation due to physical aspects: 75.19 (±1.71); pain: 71.79

(±1.37); general health status: 64.00 (±1.27); vitality: 52.84 (±1.18); social aspects: 49.93

(±1.51); limitation due to emotional aspects: 53.00 (±1.88); mental health: 53.98 (±1.11). A

total SF-36 score could be obtained through the arithmetic mean of the eight dimensions:

63.14 (±0.96). According to the EAS scores, the mean (±SE) total score was 1.40 (±0.042)

for those patients who work (n = 234); 1.73 (±0.041) for those who are housewives (n =

211); and 0.99 (±0.045) for those who are students (n = 95).

140

141

142

Discussion

There is considerable agreement on the need to recruit a high number of participants for

clinical research on psychiatric disorders in general and OCD in particular. Large sample

sizes enhance the study power to test specific hypotheses. We present the first CTOC

investigating characteristics of OCD patients and their families spanning over all areas of

OCD research. The main objective of the CTOC is to conduct multicenter research on

OCD, using properly and uniformly administered assessment instruments in order to form a

unique dataset to be used by all Consortium sites. These requirements entail a great deal of

planning, mainly to standardize the training and methods, and to constantly guarantee

cross-site reliability. Considering the remarkable heterogeneity of OCD, this approach

optimizes the findings on specific clinical phenotypes of the disorder, which is extremely

relevant for clinical, genetic, neuropsychological, neuroimaging and treatment outcome

studies.

So far, our research assessment protocol has proved to be successful. The interviews

exhibited adequate inter-rater reliability, an essential step for a multicenter initiative like

this. The continuing regular meetings have allowed CTOC members to “test” the

applicability of the assessment package and to identify current or potential problems. This

strategy also favored the clarification of several clinical questions and the immediate

correction of some quandaries, including unclear decision trees or imprecise statements.

Nevertheless, the current absence of appropriate validation of the instruments in Brazil

may, to some extent, limit some findings of our studies. As it is an ongoing research

Consortium, future papers will acknowledge this core methodological aspect.

After the first two years of active recruitment, 630 participants (much more than the

predefined goal) have been successfully evaluated and their data inserted in the core data

bank. Some caution on the external validity of all studies derived from this sample should

be taken. All CTOC centers are specialized university services or private clinics for OCD

treatment, probably comprising more severe cases. Therefore, the results cannot be directly

generalized to OCD patients from primary or secondary health care units, neither to

community samples.

It is also uncertain to what extent the results can be generalized to other countries and

cultures, despite the similar profile of the main OCD clinical features worldwide.

Brazil, only two community-based studies (restricted to big urban areas) have been

conducted. The lifetime prevalence rates of OCD found in the general population were

0.7% in Brasilia-DF, 2.1% in Porto Alegre-RS

and 0.3% in São Paulo-SP.

Most surveys

conducted in other countries and cultures have found lifetime prevalence ranging from

0.3% to 3.0%.24 Although these quite distinct estimates may reflect methodological

differences among sites, such as different interviewers’ training and skills, they are more

likely due to some regional differences in a country with so much cultural variety.

24,25

Nevertheless, the CTOC sample includes patients from different Brazilian states and

regions and the patients’ demographic and clinical characteristics differ in many aspects

between the centers, as indicated by the initial comparative analysis reported here.

143

Otherwise the sample ethnic distribution resembles the Brazilian cultural heterogeneity

(Brazilian Institute of Geography and Statistics, 2008-IBGE, available at

http//:www.ibge.org.br), since the centers from the Northeast region, in contrast with the

centers from the South, present lower frequency of Caucasian participants.

This CTOC sample also includes patients from private and public services. The longer time

gap to start treatment in the public services, when compared to the private ones, may

indicate deficiencies in the current public health system in the identification and

management of OCD cases. Considering the level of education, as measured by the number

of years of formal education, the two-year difference found between these groups, although

statistically significant, does not seem to be clinically relevant. It is worthwhile to stress

that even the participants from public services had a much higher level of education

compared to the Brazilian general population, which ranges from 4.6 years in the Northeast

to 6.6 years in the Southeast region (Brazilian Institute of Geography and Statistics, 2008-

IBGE, available at http//:www.ibge.org.br). Therefore, a possible difference on the capacity

to understand the assessment instruments by individuals from private and public services is

very unlikely. Furthermore, participants with considerable difficulties in understanding the

research questions were excluded from the study.

Although the YBOCS and D-YBOCS showed statistically significant differences between

public and private participants, one point in the YBOCS compulsions subscale and 1.4

points in the D-YBOCS total score do not seem to evince clinical relevance.

This is the first study with a large sample to evaluate OCS using a dimensional

questionnaire (DY-BOCS). The results are similar to other two previously published papers

with 48 and 137 patients,

2,10

which indicated the dimension of symmetry, order and

arrangement as the most prevalent one. Another instrument evaluating subjective

experiences of physical or mental sensations associated with repetitive behaviors (sensory

phenomena) – the USP-SPS – was also widely used for the first time. The prevalence of

sensory phenomena in this sample (65.3%) was similar to that of other studies, where they

ranged from 40% to 57.5%.

1,15,26-28

The mean score on BDI and BAI were consonant with

other international studies,

but lower than one previous Brazilian study.

The BABS

mean score was similar to that found by Phillips et al. in 198 OCD patients: 6.8 (±4.9).

Our findings concerning comorbid axis I conditions are generally in the reported ranges for

OCD clinical samples, which were differently ascertained and vary considerably. As in

most studies, major depressive disorder was the most frequent comorbid condition,

followed by anxiety disorders in general. In the literature, the rates for depressive episodes

vary from 20-67%, for specific phobias from 7% - 22%, for social anxiety disorder from 8-

42% and generalized anxiety disorder from 8-32%.

32-38

The slightly higher figures for some

disorders in our sample may be due to the fact that these patients are from specialized or

tertiary services, which usually assist more severe cases. The 7.5% prevalence of alcohol

dependence is similar to that of other clinical studies

34,39

and much lower than that of

community studies,

40,41

as expected.

There are differences regarding the types of comorbid psychiatric disorders found in

community and clinical samples, probably because of their impact on help-seeking

144

behaviors.

The CTOC sample presents a comorbidity pattern that is similar to what is

expected in clinical studies. Lifetime prevalence of mood, anxiety and tic disorders are very

similar to findings from previous studies with OCD patients who are under treatment.

26,43

On the other hand, this study presents original findings regarding the prevalence of specific

impulse control disorders that had never been systematically investigated in such a large

sample. The relatively high frequency of comorbidity with skin picking and the relatively

low frequency of compulsive sexual behavior, compulsive “interneting,” kleptomania and

pathological gambling found in this sample may serve as an additional evidence suggesting

that skin picking may be part of the obsessive-compulsive spectrum disorders

as opposed

to a more “impulsive spectrum,” which would include the other putative impulse control

disorders.

45,46

More studies in this area of OCSD are clearly needed. Addictive behaviors,

such as those involved in drug and alcohol abuse and dependence are much less frequent in

clinical samples, compared to general population samples, indicating that some OCD

sufferers may be using substances to deal with their symptoms instead of seeking

treatment.

The results regarding some aspects of the patient’s quality of life (QoL) (i.e., vitality,

social, emotional and mental health) reflect the negative impact of OCD severity and other

co-occurring symptoms (i.e., depressive, anxious). The importance of studying this aspect

is that QoL may be an appropriate indicator of treatment impact on several aspects of the

patient’s life.

Severe OCD symptoms may lead to the same levels of QoL and family

burden of schizophrenic patients, especially on psychological and social domains.

Even

with relatively mild mean scores of depression and anxiety symptoms, their additional

impact on OCD may increase the patient’s burden and, probably, of their families.

specific analyses of QoL of these patients will be described in future papers, regarding

clinical aspects that can have different impact, such as obsessions or compulsions, as

suggested by Stengler-Wenzke et al.

The CTOC participants are confident that their main goals have been successfully achieved

so far. Relevant clinical data have been systematically and uniformly collected, a large

database for collaborative studies has been built, graduate and post-graduate students are

receiving research training in this field, and expert groups are under continuous

development throughout the country. This effort will certainly generate new findings that

can contribute to the understanding and treatment of OCSD, which hopefully will lead to a

better standard of care for Brazilian patients and their families and may serve as a model to

be followed in other countries.

In conclusion, the CTOC has established an important network for recruitment and

implemented methods for standardized assessment of OCD patients in Brazil. In addition,

the chosen instruments also allowed, for the first time, a comprehensive evaluation and

measurement of multiple intrinsic and extrinsic OCD features in a large clinical sample. It

was possible, for the first time in our country, to draw a general demographic and clinical

profile of OCD patients from different regions: most of them are Caucasian, unmarried,

with some kind of occupational activity, mean age of 35 years and onset of OCS at 13 years

of age, symptoms of mild to moderate severity, higher prevalence of symmetry and

contamination/cleaning symptoms and comorbidity with depression. The present findings

145

provide a strong methodological backbone for the studies to come. Moreover, the CTOC

may pave the way to similar projects aimed at integrating other Brazilian research groups.

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148

6.2) Artigo 2: J Bras Psiquiatr, 56(3): 219-223, 2007

Transtorno obsessivo-compulsivo, parafilia, transtorno de controle de impulsos.

Key-words: Obsessive-compulsive disorder, paraphilia, impulse control disorder.

Recebido

04/06/2007

Aprovado

31/08/2007

Transtornos parafílicos em pacientes com transtorno obsessivo-compulsivo: série de casos

Paraphilic disorders among patients with obsessive-compulsive disorder: case series

Manuela C. Borges

, Lídia Ordacgi

, Rafael F. Garcia

, Bruno P. Nazar

, Leonardo F.

Fontenelle

Programa de Ansiedade e Depressão do Instituto de Psiquiatria da Universidade Federal

do Rio de Janeiro (Ipub/UFRJ).

Resumo

Com o intuito de elucidar a relação entre transtornos do controle de impulsos (TCI) e

transtorno obsessivo-compulsivo (TOC), faz-se mister estudar subgrupos mais clinicamente

homogêneos de transtornos impulsivos. Por meio do relato de quatro casos de pacientes

com TOC e diferentes tipos de transtornos parafílicos (fetichismo transvético, sadismo,

ginandromorfofilia e exibicionismo), são discutidos os conceitos de compulsividade,

impulsividade e a relação temporal entre ambos. O estudo dos casos aqui descritos mostra

que (1) pacientes com TOC e transtornos parafílicos tendem a desenvolver o TOC primeiro,

(2) diante de desejos, fantasias ou atos sexuais parafílicos, pacientes com TOC podem

lançar mão de comportamentos tipicamente compulsivos, (3) pacientes com TOC e

obsessões sexuais egodistônicas podem desenvolver desejos, fantasias ou atos sexuais

parafílicos de conteúdo semelhante ao das obsessões, (4) em um mesmo paciente, TOC e

parafilias podem apresentar cursos independentes, e (5) pacientes com TOC e parafilias

podem não apresentar obsessões sexuais. O sofrimento de pacientes com TOC e parafilias

justifica a investigação continuada de tais condições no intuito de elucidar os mecanismos

que subjazem esta associação e de criar estratégias que aumentem a adesão ao tratamento.

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Abstract

In order to elucidate the relationship between impulse control disorders and obsessive-

compulsive disorder (OCD), it is essential to study more clinically homogenous subgroups

of patients with impulsive disorders. Using four cases of patients with OCD and comorbid

paraphilias (transvestic fetishism, sadism, gynandromorphophilia, and exhibitionism) as

reference-points, we discuss the concepts of compulsivity, impulsivity, and the temporal

relationship between them. The case studies here described suggest that (1) patients with

OCD and comorbid paraphilias tend to develop OCD first, (2) once developing paraphilic

fantasies, desires, or behaviors, patients with OCD can exhibit typical compulsive

behaviors in an attempt to keep these phenomena under control, (3) patients with OCD and

ego-dystonic sexual obsessions can develop paraphilic fantasies, desires, or behaviors with

similar content to the first phenomenon, (4) OCD and paraphilias can follow independent

courses in the same patient, and (5) patients with OCD and paraphilias may not present

obsessions with sexual content. The distress presented by patients with OCD and

paraphilias give good reason for the continuous investigation of this association, aiming at

clarifying the neurobiological mechanisms underlying this association.

Introdução

A existência de um espectro obsessivo-impulsivo, com o transtorno obsessivo-compulsivo

(TOC) em um de seus extremos e os transtornos de controle do impulso (TCI) no pólo

oposto, tem sido objeto de intensa discussão na literatura (Hollander e Wong 1995). Esse

espectro englobaria transtornos que apresentam em comum uma incapacidade para

postergar ou inibir comportamentos repetitivos, e uma resposta supostamente positiva ao

tratamento com inibidores da recaptação de serotonina (IRS). Segundo o modelo hipotético

proposto por Hollander e Wong (1995), o TOC seria caracterizado por hiperfrontalidade,

aumento da função serotoninérgica e comportamentos repetitivos conduzidos, com o

objetivo de evitar acontecimentos desagradáveis. Já os TCI estariam associados à

hipofrontalidade, diminuição da função serotoninérgica e comportamentos repetitivos que

resultam eventos desagradáveis.

Os transtornos parafílicos (ou simplesmente parafilias) são caracterizados por desejos,

fantasias ou atos sexuais que envolvem a humilhação ou o sofrimento do parceiro, crianças

ou pessoas desavisadas, ou objetos não-humanos. Segundo a DSM-IV-TR, as parafilias são

exemplos de transtornos impulsivos classificados em outro local, isto é, junto aos

transtornos sexuais. Uma análise superficial do modelo de Hollander e Wong (1995) e seu

antagonismo entre compulsividade e impulsividade sugere que a associação entre TOC e

TCI, em geral, e parafilias, em particular, é rara. No entanto, diversos estudos demonstram

prevalências de transtornos de controle dos impulsos em pacientes com TOC que variam

entre 16,4% (Grant et al., 2006), 29,0% (Matsunaga et al., 2005) e 35,5% (Fontenelle et al.

2005).

A heterogeneidade destes achados reflete os diferentes conceitos de TCI adotados nestes

estudos. Por exemplo, enquanto Grant et al. (2006) avaliaram predominantemente TCI não

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classificados em outro lugar (de acordo com a DSM-IV-TR), Fontenelle et al. (2005) e

Matsunaga et al. (2005) adotaram conceitos mais amplos, incluindo neste grupo pacientes

com abuso de álcool, bulimia nervosa e parafilias (Fontenelle et al., 2005), ou mesmo

transtornos de personalidade borderline e anti-social e “impulsividade sexual” (Matsunaga

et al., 2005).

Não há dúvidas de que o conceito de TCI é demasiadamente amplo. Portanto, com o intuito

de elucidar a relação entre TCI e TOC, faz-se mister estudar subgrupos mais clinicamente

homogêneos de transtornos impulsivos. Recentemente, por exemplo, Stewart et al (2005)

constataram que pacientes com TOC e tricotilomania (um transtorno de controle dos

impulsos não classificado em outro local) caracterizaram-se por uma predominância do

sexo feminino, por apresentarem pelo menos um tique comórbido, TOC de início precoce,

número inferior de obsessões de contaminação e compulsões de verificação, e por

encontrarem-se em uso de psicoestimulantes ou venlafaxina. No presente estudo,

descrevemos quatro pacientes com uma associação entre TOC e transtornos parafílicos e

discutimos a psicopatologia destas condições à luz do chamado espectro compulsivo-

impulsivo.

Caso 1

Sr. A, um paciente do sexo masculino, 24 anos, negro, solteiro e bibliotecário, apresentou

os primeiros sintomas obsessivo-compulsivos aos 16 anos, quando começou a sentir

necessidade de pisar quatro vezes no pé da porta, antes de entrar. Pouco depois,

desenvolveu obsessões de cunho sexual envolvendo seu pai (por exemplo, “ele quer que eu

fique louco” e “ele quer transar comigo”) e outros pensamentos repetitivos e desagradáveis

que incluíam dúvidas como “será que eu tirei a virgindade das minhas irmãs?” e “será que

eu tive orgasmo com o empregado homossexual lá de casa?”.

Em resposta a esses pensamentos, o Sr. A executava comportamentos como piscar oito

vezes, repetir o próprio pensamento e cruzar a perna por quatro vezes. Outras compulsões

presentes incluíam a necessidade de subir e descer de sua moto duas vezes, cantar uma

música para “ficar protegido” e pisar de uma maneira especial por cinco vezes, cada vez

que pisava em falso, por achar que isso era “coisa de homossexual”.

Dois anos mais tarde, o Sr. A passou a usar roupas íntimas das irmãs durante a

masturbação. Sempre tentava atingir um total de quatro episódios masturbatórios, que eram

seguidos por muita culpa. Depois da masturbação, o paciente não só feria seus braços e

pernas, como forma de expiação, também realizava outros comportamentos compulsivos

descritos anteriormente, como a repetição de rituais um determinado número de vezes. Seus

diagnósticos foram TOC e fetichismo transvéstico.

Entre as drogas utilizadas pelo Sr. A, por dose e tempo adequados, encontravam-se

fluoxetina e paroxetina potencializadas por risperidona, tioridazina e carbamazepina. Após

ser admitido em nosso serviço sem medicações, o paciente fez uso de fluoxetina 80 mg e

alprazolam 2 mg, sem apresentar melhora. Cerca de quatro meses depois, o paciente

abandonou o tratamento.

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Caso 2

Sr. B, um paciente do sexo masculino, 44 anos, branco, casado e dentista, apresentou os

primeiros sintomas aos 6 anos, quando começou a fazer gestos obscenos, a piscar e a bater

na parte superior das portas. Desde aquela época, é tomado por uma imagem em que é

violentado sexualmente e pela idéia de que seus parentes seriam aleijados, cegos e doentes.

Na época de admissão em nosso serviço, apresentava tiques faciais, como piscar

excessivamente e mostrar a língua, e fônicos, como fungar, tossir e pronunciar palavras

obscenas. Tiques complexos, como girar os braços, também estavam presentes. Além disso,

mantinha obsessões somáticas e de agressão.

Desde os 18 anos, o Sr. B apresentava fantasias sexuais nas quais era um executivo que

espanca, humilha e abusa de sua secretária. As fantasias eram acompanhadas por

masturbação. O paciente imaginava tais situações e se masturbava todos os dias antes de

dormir, mesmo com a esposa ao lado, o que interferia significativamente em seu

relacionamento marital. Os diagnósticos do Sr. B foram síndrome de La Tourette, TOC e

sadismo sexual.

O paciente procurou tratamento pela primeira vez aos 26 anos. Ao longo de sua vida, Sr. B

fez uso de vários medicamentos, incluindo risperidona, clonazepam, flufenazina,pimozida e

bromazepam. Em nosso serviço, o paciente foi tratado com quetiapina em doses de até 100

mg/dia. Sr. B relatou melhora parcial dos pensamentos obsessivos após quatro semanas. No

entanto, o desenvolvimento de sonolência impediu acréscimos adicionais da dose. Durante

todo o seguimento, suas fantasias sexuais se mantiveram inalteradas e os tiques evoluíram

com flutuações importantes. O paciente abandonou o tratamento após cerca de seis meses.

Caso 3

Sr. C, um paciente do sexo masculino de 40 anos, pardo, solteiro e digitador, apresentou os

primeiros sintomas aos 8 anos, quando começou a “falar para encher o tempo”. Esse

sintoma persiste até hoje, e enquanto o Sr. C não completa o raciocínio, repete as sílabas

“sé, sé, sé, sé...”. Ao ser admitido em nosso serviço, o paciente ainda apresentava obsessões

de contaminação, como preocupação com sujeira e micróbios e vasto número de

compulsões, como contar as próprias fezes, interromper a evacuação para dar descarga,

lavar cada parte do corpo sete vezes e alinhar quadros em sua parede. O Sr. C também

colecionava objetos, como copos, miniaturas, animais empalhados, figurinhas, bonecos,

discos, CDs e placas de trânsito.

O paciente apresentava, desde o início da idade adulta, fantasias envolvendo homens com

aspectos feminilizados (travestis), com quem ocasionalmente mantinha contato sexual. O

Sr. C permanecia horas perambulando pelas ruas onde os travestis trabalhavam durante a

noite. Sentia-se profundamente atraído pela curvas dos travestis e essa fantasia não o

preocupava. Dizia ser “um garanhão” e ter muitas parceiras. Seus diagnósticos foram

transtorno de tique fônico crônico, TOC e ginandromorfofilia.

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Em nosso serviço, o paciente foi medicado com fluoxetina, em doses de até 60 mg/dia.

Embora tenha apresentado melhora parcial dos sintomas obsessivo-compulsivos, o paciente

desenvolveu náusea, o que motivou a interrupção do tratamento várias vezes, com piora dos

sintomas. Foi então medicado com clomipramina, até 50 mg/dia, mas o paciente passou a

se queixar de sonolência e cansaço, o que o levou a abandonar o tratamento após menos de

três meses. Durante todo o período de seguimento, o quadro de ginandromorfofilia

permaneceu inalterado.

Caso 4

Sr. D, um paciente do sexo masculino de 22 anos, negro, solteiro e professor, apresentou as

primeiras compulsões de simetria e organização aos 13 anos. Relatava organizar seus livros

em casa cuidadosamente e empilhá-los sempre da mesma maneira antes de iniciar uma

aula. Sr. D afirmava ainda ter em casa todos os testes e provas que já fez durante a vida

organizados em pastas. Percebia um odor desagradável originário de suas axilas ao fim da

jornada de trabalho. Esse odor não era perceptível para as outras pessoas. O paciente

evitava se envolver em atividades sociais imediatamente depois do trabalho, pois acreditava

que esse cheiro poderia incomodar e constranger seus colegas. Além disso, ao dormir em

companhia de sua namorada, acordava no meio da noite para tomar banho e passar

desodorante.

Aos 18 anos, passou a exibir seus genitais a mulheres desavisadas. O paciente gastava horas

perambulando pelas ruas, todos os dias, em busca de uma situação que possibilitasse o

comportamento exibicionista. Dizia perder noites inteiras procurando uma oportunidade

para exibir sua genitália. Preferia exibir seus genitais a mulheres que se vestissem “como

piranhas” e ficava excitado, tanto com reações de repulsa quanto de curiosidade por parte

das mulheres.

Afirmava atingir o orgasmo invariavelmente ao notar que sua vitima olhava seu pênis. O

paciente masturbava-se repetidamente pensando nas mulheres a quem já havia se exibido.

Os diagnósticos do Sr. C foram TOC e exibicionismo.

Ao ser admitido em nosso serviço, foi medicado com venlafaxina, 75 mg/dia, com melhora

discreta dos sintomas obsessivo-compulsivos ao final de um mês. O quadro de

exibicionismo, no entanto, permaneceu inalterado. Logo em seguida, o paciente abandonou

o tratamento.

Discussão

Embora diversos estudos apontem para uma associação entre o TOC e os TCI, a

heterogeneidade dos TCI dificulta enormemente a elucidação das relações entre tais

condições, tanto do ponto de vista dos sintomas quanto do curso, da resposta tratamento e

dos substratos neurais subjacentes. O estudo de populações mais homogêneas do ponto de

vista clínico pode ajudar de maneira significativa na compreensão da complexa relação

entre pacientes com TOC e TCI. Daí a importância de investigar a relação entre o TOC e

um TCI em específico, por exemplo, as parafilias. Nossa série de casos aqui relatada pode

representar um importante passo neste sentido.

153

Os casos aqui descritos sugerem que, quando ocorre uma associação entre o TOC e

transtornos parafílicos, o TOC tende a surgir primeiro. De fato, este curso de aparecimento

dos sintomas parece refletir o período habitual de desenvolvimento dos transtornos

psiquiátricos em análise. Em outras palavras, pacientes com TOC costumam apresentar

início precoce ou até mesmo pré-puberal dos sintomas (Rosário-Campos et al., 2001;

Fontenelle et al., 2003), enquanto pacientes com parafilias só apresentam os sintomas deste

transtorno quando se encontram em um estágio mais avançado do desenvolvimento

psicossexual (Grant, 2005). A relação temporal entre os transtornos psiquiátricos aqui

descritos também contradiz a hipótese de que o TOC possa ser uma condição secundária às

parafilias, ou seja, uma tentativa de suprimir desejos, fantasias ou atos sexuais inaceitáveis

(Stein, 1994).

No entanto, o paciente já portador de TOC, uma vez desenvolvendo uma parafilia, pode

lançar mão de comportamentos compulsivos na tentativa de anular ou de manter seus

desejos, fantasias ou atos sexuais sob controle. Por exemplo, no caso 1, o Sr. A utilizava

roupas íntimas da irmãs durante a masturbação e, logo após o orgasmo, feria seus braços e

pernas como forma de expiação, além de repetir atividades rotineiras determinado número

de vezes. De fato, existem alguns relatos na literatura que sugerem que fantasias parafílicas

podem apresentar características egodistônicas, como aquelas presentes em um pensamento

tipicamente obsessivo (Abdo et al., 2001). Uma outra possibilidade seria a de que um

paciente com TOC com imagens sexuais egodistônicas pudesse se sentir sexualmente

atraído pelo conteúdo de tais vivências mediante sua repetição e habituação. Nesta linha, o

Sr. B (caso 2) apresentava, na infância, imagens nas quais ele mesmo era violentado e seus

parentes aleijados, cegos e doentes. Posteriormente, aos 18 anos, o Sr. B passou a

apresentar fantasias sexuais nas quais era um executivo que espancava, humilhava e

abusava. Mais estudos centrados na psicopatologia das obsessões, dos impulsos e das

compulsões nos parecem apropriados para que a relação entre estes fenômenos seja

esclarecida.

Os casos 3 e 4 sugerem que pacientes com TOC e parafilias podem não lançar mão de

comportamentos compulsivos na tentativa de anular ou de manter seus desejos, fantasias ou

atos sexuais sob controle [os quais podem ser egossintônicos (caso 3)] ou mesmo sequer

apresentar obsessões de conteúdo sexual dentre os seus sintomas obsessivo-compulsivos

(casos 3 e 4). Os fatores que determinam o surgimento de compulsões “antifantasias” ou a

transformação de obsessões sexuais egodistônicas em fantasias egossintônicas devem ser

investigados em estudos futuros com amostras maiores.

Todos os pacientes descritos no presente relato apresentaram graves problemas quanto à

adesão ao tratamento. As razões para este fenômeno são desconhecidas, mas podem incluir

vergonha ou constrangimento diante do relato de seus sintomas sexuais aos profissionais

responsáveis por seus cuidados clínicos. Estas vivências podem ser particularmente

intensas em pacientes com TOC, sabidamente conscienciosos.

Fontenelle et al. (2005) sugeriram que pacientes com a comorbidade entre TOC e TCI

requerem um maior número de ensaios terapêuticos com IRS até alcançar resposta

terapêutica. Portanto, é possível que, mediante um incremento da adesão ao tratamento,

154

alguns pacientes com TOC e parafilias respondam adequadamente à medicação instituída.

De fato, embora alguns estudos sugiram que os IRS podem ser eficazes no manejo de

pacientes com parafilias (Zohar et al., 1994; Abouesh e Clayton, 1999), tais medicações

não demonstraram ser eficazes em outros pacientes, especialmente aqueles com sintomas

parafílicos egossintônicos (Abdo et al., 2001).

De qualquer forma, a adesão ao tratamento se torna ainda mais importante diante das

evidências de que algumas classes de drogas podem ser eficazes, tanto no TOC resistente

ao tratamento quanto nas parafilias, incluindo o acetato de ciproterona (Casas et al., 1986;

Feldman et al., 1988; Gijs e Gooren, 1996), os hormônios liberadores da gonadotrofina [por

exemplo, triptorelina (Eriksson, 2000; Eriksson, 2007; Briken et al., 2003)] e alguns

anticonvulsivantes [por exemplo, topiramato (Khazaal e Zullino, 2006; Marazziti e

Dell’Osso, 2006; Hollander e Dell’Osso, 2006; Van Ameringen et al., 2006)].

Conclusão

Nosso estudo sugere que TOC e parafilias podem se associar em um mesmo paciente,

observação esta inconsistente com a visão de que compulsividade e impulsividade devem

ser consideradas pólos opostos do espectro compulsivo impulsivo. Nosso estudo sugere que

(1) pacientes com TOC e transtornos parafílicos tendem a desenvolver o TOC primeiro, (2)

diante de desejos, fantasias ou atos sexuais parafílicos, pacientes com TOC podem lançar

mão de comportamentos tipicamente compulsivos, (3) pacientes com TOC e obsessões

sexuais egodistônicas podem desenvolver desejos, fantasias ou atos sexuais parafílicos, (4)

em um mesmo paciente, TOC e parafilias podem apresentar cursos independentes e (5)

pacientes com TOC e parafilias podem não apresentar obsessões sexuais. Pacientes com

TOC e transtornos parafílicos apresentam pouca adesão ao tratamento por razões ainda

desconhecidas. O sofrimento de pacientes com TOC e parafilias justifica a investigação

continuada de tais condições no intuito de elucidar claramente os mecanismos que

subjazem esta associação e de criar estratégias que aumentem a adesão ao tratamento.

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6.3) Artigo 3: Journal of Psychiatric Research 43 (2009) 455–463

Empathy and symptoms dimensions of patients with obsessive–compulsive disorder

Leonardo F. Fontenelle

a,b,

Isabela D. Soares

, Flavia Miele

, Manuela C. Borges

Angélica M. Prazeres

, Bernard P. Rangé

, Jorge Moll

Anxiety and Depression Research Program, Institute of Psychiatry, Federal University of

Rio de Janeiro, Rio de Janeiro, Brazil

Department of Psychiatry and Mental Health, Institute of Community Health, Fluminense

Federal University, Niterói, Brazil

Postgraduate Program in Psychology, Institute of Psychology, Federal University of Rio de

Janeiro, Rio de Janeiro, Brazil

Brain Morphometry and Investigative Neuroimaging, LABS-D’Or Hospital Network, Rio

de Janeiro, Brazil

Received 7 April 2008; received in revised form 24 May 2008; accepted 27 May 2008

Abstract

Patients with obsessive–compulsive disorder (OCD) often display cognitions and/or

behaviors that may well reflect the existence of ‘‘hyper-attachment” to different

environmental elements, including their offspring, family members, divine entities, or even

inanimate objects. Based on the fact that both OCD symptoms and physiologic

interpersonal attachment mechanisms involve overlapping ventral fronto-limbic circuits, we

hypothesized that there is a relationship between empathy, evaluated with the Interpersonal

Reactivity Index (IRI), and OCD symptom dimensions. We evaluated 53 patients with

OCD and 53 age-and sex-matched individuals from the community with the Structured

Clinical Interview for the Diagnosis of DSM-IV axis I disorders, the Saving Inventory-

Revised, the IRI (composed of four sub-scales), the Obsessive–Compulsive Inventory –

Revised, the Beck Depression Inventory, and the Beck Anxiety Inventory. Patients with

OCD displayed greater levels of affective empathy (i.e., empathic concern (p = 0.006) and

personal discomfort (p < 0.001)) than community controls. In bivariate analyses, the

severity of hoarding symptoms of patients with OCD correlated with empathic concern (r =

0.39; p < 0.001), fantasy(r = 0.36; p < 0.01), and personal discomfort(r = 0.39; p < 0.001).

In partial correlation analyses adjusting for comorbid depression and anxiety, only the

association between hoarding and fantasy remained robust(r = 0.41; p < 0.001).A model

that included severity of hoarding, depression, and anxiety symptoms predicted 33% of the

variance on the fantasy scale. Our findings suggest that hoarding is linked to specific

aspects of interpersonal reactivity. Comorbid depression and anxiety, however, explain a

large proportion of the empathic profile exhibited by patients with OCD.

158

Keywords: Obsessive–compulsive disorder; Hoarding; Empathy

1. Introduction

There is no dispute that empathy – the capacity to understand and share emotional

states of others in reference to oneself – plays a critical role in human interpersonal

engagement and social interaction (Decety and Moriguchi, 2007). Nevertheless, it has been

argued that empathy is not a unitary system but rather a loose collection of

partiallydissociable neurocognitive systems. In particular, three main divisions have been

made: cognitive empathy (or Theory of Mind), emotional empathy, and motor empathy

(Blair, 2005). Several neuropsychiatric disorders have been shown to present deficits in

different types of empathic abilities including schizophrenia (Montag et al., 2007),

Asperger syndrome (Rogers et al., 2007), psychopathy (de Oliveira-Souza et al., 2008),

brain injury (Shamay-Tsoory et al., 2004), and frontotemporal lobar degeneration (Rankin

et al., 2005).

An important emerging concept is that empathic abilities may strongly rely on the

neurobiology of social attachment or bonding, which has been extensively studied in

animals (Insel, 1997; Young andWang, 2004) and, more recently, in humans (Bowlby,

1988; Moll et al., 2006, 2008; Krueger et al., 2007). Interestingly, patients with obsessive–

compulsive disorder (OCD) often show cognitions and/or behaviors that may well reflect

the existence of ‘‘hyper-attachment” or excessive bonding to different environmental

elements, including their offspring or close family members (e.g., in post-partum ‘‘maternal

preoccupations” – Leckman and Herman, 2002); divine entities (Birgegard and Granqvist,

2004) (e.g., in religious scrupulosity – Nelson et al., 2006) or even inanimate objects (e.g.,

in the compulsive hoarding syndrome – Frost et al., 1995). In the present paper, we will

address the possible links between OCD symptom dimensions and empathy.

Although it is unquestionable that OCD is a homogeneous disorder in terms of form

(i.e., the presence of obsessive thoughts and/or compulsive rituals), there is a large

variability in terms of symptoms content. For example, in a recent review paper of 12

principal-components and confirmatory factor analytic studies involving over 2000 patients

with OCD, at least four symptom dimensions were consistently extracted:

symmetry/ordering, contamination/ cleaning, obsessions/checking, and hoarding (Mataix-

Cols et al., 2005). These dimensions were associated with distinctive clinical, biological

and outcome features. The evidence supporting the hoarding dimension was particularly

robust (Mataix-Cols et al., 2005).

In fact, the so-called ‘‘compulsive hoarding syndrome” in OCD has been associated

with several differential features, including earlier age at onset (Samuels et al., 2002;

Fontenelle et al., 2004); worse social functioning (Saxena et al., 2002; Frost et al., 2000;

Lochner et al., 2005; Wheaton et al., 2008); lower insight into symptoms (Damecour and

Charron, 1998; Storch et al., 2007); higher rates of past traumatic events (Hartl et al., 2004;

LaSalle-Ricci et al., 2006); greater frequency of certain types of OCD symptoms (e.g.,

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symmetry/ordering) and comorbid axis I and II disorders (Frost et al., 2000; Samuels et

al.,2002; Fontenelle et al., 2004; Lochner et al., 2005; LaSalle-Ricci et al., 2006); specific

COMT polymorphisms and linkage to a region on chromosome 14 (Lochner etal., 2005;

Samuels et al., 2007a,b); higher frequency of hoarding among first-degree members

(Samuels et al., 2007a); distinguished neuroanatomical (Saxena et al., 2004) and

neuropsychological (Lawrence et al., 2006) underpinnings; possible dopaminergic

involvement (Stein et al., 1999), and poorer treatment outcome to serotonin-reuptake

inhibitors (Black et al., 1998; Winsberg et al., 1999; Mataix-Cols et al., 1999), cognitive

behavioral therapy (Mataix-Cols et al., 2002), or their combination (Frost et al.,2000).

It is difficult to speculate on the role of social cognition in OCD in general and

obsessive–compulsive symptoms dimensions in particular, but empathic abilities could

provide an additional paradigm aimed at disentangling different sub-types of OCD and at

searching for additional dimensions of neurobiological significance. It could be the case,

for example, that increased levels of empathy could lead to an overvaluation of certain

thoughts (Obsessive–Compulsive Cognitions Working Group – OCCWG, 1997) with

aggressive (i.e., ‘‘I fear acting unwanted impulses (e.g., stabbing my children)”), sexual

(i.e., ‘‘I am afraid of having sexual behavior toward other people”), or even contamination

themes (i.e., ‘‘I am concerned that will get others ill by spreading contaminants”), resulting

in full-formed obsessions of the so-called ‘‘obsessionschecking” dimension of OCD.

One additional, perhaps more significant, role of empathic abilities in OCD could be

that played by a close construct, i.e., emotional attachment, in certain hoarding behaviors.

Although DSM-IV and Yale-Brown Obsessive–Compulsive Scale (YBOCS) suggest that

hoarding involves only non-sentimental saving, several studies contradict this assumption

(Frost et al., 1998). On the basis of some clinical observations, for example, it could be

argued that hoarding may be one way of expressing increased levels of empathic abilities

or, more speculatively, that empathymay represent some sort of cognitive or affective

counterpart of some types of hoarding.

For example, Frost and Gross found that hoarders reported more sentimental saving

and greater emotional attachment to possessions than non-hoarders. In fact, many hoarders

see their possessions as extensions of their bodies, i.e., when other people touch or move

their belongings; the hoarders tend to feel violated (Frost et al.,1995). For other individuals,

some possessions may serve as meaningful reminders of important past social events and

getting rid of them may sound like the loss of a close friend. Some hoarders may even

impart human qualities to their possessions or ‘‘anthropomorphize” them (Greenberg,

1987). On the other hand, hoarders may extend their emotional attachment to another level,

accumulating not only objects, but also living beings, including animals and friends; a

phenomenon that could mimic increased interpersonal empathy and social bonding. Finally,

there may be some biological commonalties between empathy and OCD, particularly

hoarding. For example, oxytocin has been consistently implicated in the mechanisms

underlying empathy in humans. For example, Domes et al. (2007) found that, compared to

placebo, 24 UI of intranasal oxytocin improved the performance of normal subjects on the

Reading the Mind in the Eyes Test. On the other hand, a handful of studies have found

increased levels of oxytocin in the cerebrospinal fluid of patients with OCD (Leckman et

al., 1994). Neuroimaging studies have also provided important evidence linking brain

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systems involved with attachment responses and pro-social behaviors. Decisions to donate

to charitable organizations and decisions to cooperate based on trust were associated with

activation of the septal and sub-genual regions (Moll et al., 2006; Krueger et al., 2007),

which are intimately linked to mechanisms of social bonding and oxytocin release by the

anterior hypothalamus (Freedman et al., 2000).

Based on the aforementioned findings, we predicted that patients with OCD and

hoarding symptoms would exhibit increased levels of affective and cognitive empathic

abilities. If our hypothesis is correct, hoarding may be the ultimate result of a social

neurocognitive system in overdrive or, more speculatively, the gregariousness presented by

some patients with OCD may be a forme fruste of ‘‘interpersonal” hoarding. Speculations

aside, we believe that the study of interpersonal aspects, especially empathic concern, of

patients with OCD, may be of significant interest in order to clarify the cognitive and

affective aspects underling pathological hoarding behavior in OCD.

The objectives of this study were (1) to compare patients with OCD and individuals

from the community in terms of interpersonal reactivity according to scores obtained on the

IRI and (2) to evaluate the relationship between the severity of different OCD dimensions

(according to the OCI and the SI-R) with the patterns of interpersonal reactivity as

measured by the IRI.

2.Methods

Patients were consecutively selected among those under treatment in (1) the Anxiety

and Depression Research Program at the Institute of Psychiatry of the Federal University of

Rio de Janeiro (IPUB/UFRJ), (2) the Division of Applied Psychology at the Institute of

Psychology of the same university (DPA/UFRJ), and (3) the first author’s private practice.

The inclusion criteria were (1) the diagnosis of OCD, with or without psychiatric

comorbidity confirmed by means of the Structured Clinical Interview for Axis I disorders

(SCID), (2) age between 18 and 80 years, and (3) absence of any other neurological,

endocrinological, or systemic disorder that could interfere in our results. In the presence of

any psychiatric comorbidity, only patients who developed OCD as a primary disorder,

either in terms of chronology or in terms of severity of symptoms, were included.

The control group consisted of individuals recruited in the community by means of

local advertisements, and included members of the medical and administrative staff of the

Federal University of Rio de Janeiro. The inclusion criteria for volunteers selected to

participate in the control group were (1) age between 18 and 80 years, and (2) absence of

any other neurological, endocrinological, or systemic disorder that could interfere in our

results. Community controls were not evaluated a priori for the presence of psychiatric

disorders. With this strategy, we intended to avoid the selection of a ‘‘supernormal”

sample, which would be not representative of the general population.

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2.1.

Procedures

The local institutional review board approved this research protocol (SISNEP code

= CAAE -0002.0.249.000-07). All participants signed an informed consent after a detailed

explanation of the procedures involved in the study. Patients with OCD, but not controls,

were evaluated with the Brazilian version of the SCID-IV (Del-Ben et al., 2001). The

SCID-IV is a semi-structured clinical interview to be administered by the clinicians in order

to identify axis I diagnosis according to the DSM-IV criteria. Since two different centers

(IPUB/UFRJ and IP/UFRJ) were responsible for the recruitment and administration of the

SCID in the majority of cases, some questions regarding the reliability of our methods

could be raised. Nevertheless, the simultaneous psychiatric (Anxiety and Depression

Research Program) and psychological (Division of Applied Psychology) follow-up of a

significant portion of patients allowed us to discuss and reach a consensus on cases

presenting difficult diagnoses.

A socio-demographic questionnaire was administered to both patients and controls

including the following information: age, gender, educational level, marital and

employment status, and monthly income. A clinical questionnaire was employed to gather

patients’ data on the age at onset of sub-clinical obsessions and/or compulsions (i.e., the

age in which the patient remember first presented obsessive–compulsive symptoms without

distress or impairment), different psychiatric comorbidities according to the SCID, and

current therapeutic strategies.

2.2.

Instruments

2.2.1. Saving inventory – revised (SI-R)

The SI-R was developed by Frost et al. (2004) and validated to Brazilian Portuguese

by Soares (2007). The SI-R is aimed to evaluate the severity of hoarding behaviors in

clinical and non-clinical populations. It is a self-administered Likert Scale that includes 23

items. The items are divided in three sub-scales: the clutter sub-scale (9 items), the difficult

discarding sub-scale (7 items) and the acquisition sub-scale (7 items). A detailed

description on the psychometric properties of the Brazilian version of the SI-R is available

upon request.

2.2.2. Beck depression inventory (BDI)

The BDI is one of most used self-rated instruments to evaluate the severity of

depression in different populations. The scale has 21 items, each consisting of four

statements describing increasing intensities of symptoms of depression. Items are rated on a

scale from 0 to 3, reflecting how participants have felt over the past week. Possible scores

range from 0 to 48; higher scores reflect more severe depressive symptoms. The BDI was

validated to Brazilian Portuguese by Cunha (2001).

2.2.3. Beck anxiety inventory (BAI)

The BAI is a self-rated instrument to evaluate the severity of anxiety in different

populations. The scale has 21 items describing subjective, somatic, or panic-related

symptoms, each consisting of four statements about physiological and cognitive

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components of anxiety. It was specifically designed to reduce the overlap between

depression and anxiety scales by measuring anxiety symptoms shared minimally with those

of depression. Items are rated on a scale from 0 to 3, reflecting how participants have felt

over the past week. Possible scores range from 0 to 63; higher scores reflect more severe

anxiety symptoms. The BAI was validated to Brazilian Portuguese by Cunha (2001).

2.2.4. Obsessive–compulsive inventory – revised (OCI-R)

The OCI-R, developed by Foa et al. (2002), is a revised and shorter version of the

Obsessive–Compulsive Inventory (OCI), an instrument created by the same group of

investigators (Foa et al., 1998). The OCI-R evaluates the severity of a series of obsessive–

compulsive symptoms. The OCI-R is a Likert scale that contains 18 items and is self-

administered. It provides a total score and six sub-scores, including washing, checking,

ordering, rumination, hoarding, and neutralization. Recently, the OCI-R was translated and

adapted to Brazilian Portuguese by Souza et al. (2008).

2.2.5. Interpersonal reactivity index (IRI)

The IRI, developed by Davis (1983), is the most used self-administered instrument

to assess the different components of empathy. The IRI includes 28 items divided in four

sub-scales (2 cognitive and 2 affective scales). Each answer score can vary from 0 (does not

describe me well) to 4 (describes me very well). The scores of each sub-scale are calculated

individually. The IRI does not provide a total score since each sub-scale evaluates an

independent component of empathy (D’Orazio, 2004).We employeda Brazilian Portuguese

version of the IRI provided by Oliveira-Souza and Moll (unpublished version).

The IRI cognitive sub-scales include the ‘‘perspective taking” and the ‘‘fantasy”

sub-scales. The ‘‘perspective taking” sub-scale evaluates the tendency that an individual

has to adopt, spontaneously, the psychological point-of-view of another person (e.g., I

sometimes try to understand my friends better by imagining how things look from their

perspective). The ‘‘fantasy sub-scale” evaluates the tendency that the individual has to

identify him or herself with fictitious personages, such as book, films, or plays characters

(e.g.,I really get involved withthe feelings of the characters in a novel). The IRI affective

sub-scales include the ‘‘empathic concern” and the ‘‘personal discomfort” sub-scales. The

empathic concern sub-scale refers to the feelings of compassion, tenderness and concern for

the others (e.g., I often have tender, concerned feelings for people less fortunate than me).

The ‘‘personal discomfort” sub-scale evaluates self-oriented anxiety and discomfort

resulting from tense personal situations (e.g., I sometimes feel helpless when I am in the

middle of a very emotional situation).

2.3. Statistical analyses

Fifty-three patients with OCD and 53 age-and gender-matched individuals from the

community had their categorical variables compared by means of the v 2 test and their

continuous variables (including their scores on the BDI, BAI, OCI-R, SI-R and IRI)

compared by means of the Student’s t-test. We adopted standard deviation as measure of

variability. For the correlation analyses, only patients with OCD were selected. Bivariate

Pearson’s correlation analyses were performed using IRI, OCI-R, and the SI-R total and

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partial scores. Partial analyses including these variables and controlling for the BDIand

BAI scores were also performed. The level of statistical significance was 5%.

3.Results

3.1. Description of the sample

At first, a total of 135 participants fulfilled our inclusion criteria: 65 patients with

OCD and 70 community individuals. The volunteers were predominantly female

individuals (n = 82; 60.7%) with a current mean age of 37.3 (±13.5) years. Sixty-nine

(51.1%) participants were single, 48 (35.6%) were married, 7 (5.2%) were divorced, 6

(4.4%) were separated and 5 (3.7%) were widowed. The volunteers had a mean of 13.2±4.1

years of education and 78 (57.8%) were employed. Their mean monthly income was 2.120

(±2.172) reais (about 1.100 American dollars). A comparison between the socio-

demographic characteristics of our patients with OCD and volunteers from the community

is depicted in Table 1. Although the mean monthly income of patients with OCD was lower

than that of community controls, this difference did not reach statistical significance.

In terms of OCD patients, 47 (72.3%) were selected from the sample being treated

in the Anxiety and Depression Research Program from the IPUB/UFRJ, 10 (15.4%) from

the Division of Applied Psychology of the IP/UFRJ, and 8 (12.3%) from the first authors’

private practice. Although it was tempting to compare patients recruited in different centers,

the low numbers precluded valid analyses. In general lines, however, they were similar

from the socio-demographic point-of-view.

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Patients with OCD reported the onset of obsessions and compulsions at 14.5±10.5

and 15.9±12.7 years, respectively. In terms of comorbid disorders, 35.9% of the patients

with OCD exhibited a current major depressive episode; 6.3% had social phobia and 6.3%

presented a dysthimic disorder. The low prevalence of comorbid conditions may be

attributed by transversal nature of the study and by the fact that patients were under

psychological and/or pharmacological treatment. For example, 79.7% of patients were

under a serotonin reuptake inhibitor, 40% were using a benzodiazepine, and 32.3% were

under an antipsychotic. Further, 32.3% of the patients were being treated with cognitive

behavioral therapy.

3.2. Main findings

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Patients with OCD and controls were matched according to age and gender,

generating two groups of 53 participants each, for the comparison of the profiles of

response on the IRI, as seen in Table 2. All patients with OCD (n = 65) were included in

the bivariate Pearson’s correlation analyses (Table3) and the partial analyses controlling for

the BDI and BAI scores (Table4).

Patients with OCD displayed greater levels of affective empathy (i.e., empathic

concern (p = 0.006) and personal discomfort (p < 0.001)) than community controls. In

bivariate analyses, the severity of hoarding symptoms of patients with OCD correlated with

empathic concern (r = 0.39; p < 0.001), fantasy (r = 0.36; p < 0.01), and personal (r = 0.39;

p < 0.001). In partial correlation analyses adjusting for comorbid depression and anxiety,

only the association between hoarding and fantasy remained robust (r = 0.41; p < 0.001).

Female patients with OCD displayed significantly greater scores on the personal distress

scale than male patients (t =



3.21, df = 50, p = 0.002).

Since only the IRI fantasy scores were independently associated with a particular

obsessive–compulsive symptom dimension, we decided to perform a specific stepwise

regression analysis using fantasy as the dependent variable and the BAI, BDI, OCI-R

dimensions, and the SI-R scores as independent ones. We found that a model that included

severity of depression, anxiety, and hoarding predicted 33% of the variance on the fantasy

scale (Table5).

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4. Discussion

We found that patients with OCD presented significantly higher levels of affective

empathy (i.e., empathic concern and personal discomfort) than community individuals.

Although, as predicted, statistically significant correlations were found between the two

forms of affective empathy and the severity of hoarding behaviors, similar correlations

were found between empathic concern and personal discomfort with other obsessive–

compulsive symptoms, such as ordering, checking and washing. Further, a subsequent

analysis revealed that the severity of comorbid symptoms of depression and anxiety largely

explained the correlations between affective empathy and obsessive–compulsive symptoms

in patients with OCD.

Leckman and Cohen (1999) suggested that patients with Tourette syndrome (TS), a

condition biologically linked to some forms of OCD, are ‘‘sensitive to the feelings and

experiences of others, and have a thinner barrier to stimulation” (also termed

‘‘somatosensory hyper-awareness”). Although this was an untested clinical observation,

findings from other controlled studies on TS are interesting in this regard. Harrison et al.

(2007) compared the profile of response on the IRI of patients with TS with (n =30) and

without (n = 40) echopraxia. In this study, patients with TS and echopraxia exhibited higher

scores on the IRI’s empathic concern, personal discomfort, and fantasy scores than patients

with TS without echopraxia. Although this evaluation was somewhat restricted, it would

also be interesting to test whether patients with TS and obsessive–compulsive symptoms

describe increased levels of interpersonal reactivity. Interestingly, echophenomena were

already associated with the presence of increased obsessionality in TS (Robertson et al.,

1988).

The fact that patients with OCD displayed increased levels of empathic concern

than community controls is apparently in contrast to some recent findings. For example,

Bejerot et al. (2001) described autistic traits in up to 20% of their OCD patients. This same

group has insisted on the existence of an autistic sub-type of patients with OCD that would

be characterized, among other features, by increased severity of hoarding behaviors

(Bejerot, 2007). Since pervasive developmental disorders are associated with decreased

167

levels of empathy (Rogers et al., 2007), we believe that the inconsistence between our study

findings and those described by these authors (Bejerot et al., 2001) can be ascribed to the

different psychopathological concepts of pathological hoarding behaviors (Maier, 2004)

and to our inclusion criteria: Firstly, pathological hoarding may include diverse forms of

symptoms, such as compulsive, impulsive, or stereotypic behaviors (Maier, 2004).

Secondly, in our study, patients with developmental disorders were preliminarily excluded

(n = 2). These conceptual and methodological aspects may have contributed to a sample

free of severe pathologies of the central nervous system whose repetitive behaviors may be

best understood as stereotypes, and not obsessive–compulsive behaviors.

We found that correlations between empathic concern and obsessive–compulsive

symptoms were no longer significant when the effects of comorbid anxiety and depression

were controlled for. Since correlation analyses do not allow inferences about causalities,

these findings can be interpreted in at least two not mutually excludable ways: (1) empathic

concern is a symptom of anxious or depressed patients with OCD and/or (2) increased

levels of empathic concern among patients with OCD is a risk-factor for greater severity of

comorbid anxiety and/or depression.

In support for the first assertion, Griens et al. (2002) found that changes in the

Neuroticism and Extraversion dimensions of the NEO Five-Factor Inventory (which

assesses the five major domains of the five-factor model of personality (neuroticism,

extraversion, openness, agreeableness, and conscientiousness) and, most importantly, in the

‘‘interpersonal awareness” scores of the Interpersonal Sensitivity Measure (IPSM), related

strongly to the decrease in depression severity of 80 patients with depressive disorders

after12 weeks of treatment with psychotherapy and/or drugs. Therefore, we cannot discard

the possibility that empathic concern represents a ‘‘state”,as opposed to a ‘‘trait” feature

attributable to greater levels of depression (and maybe anxiety) symptoms.

If increased levels of empathic concern predisposes to depression, guilt feelings

may mediate this relationship (O’Connor et al., 2007). For example, a study with daughters

of depressed mothers found that increased levels of empathy related to the maternal

suffering were associated to inadequate problem-solving strategies and feelings of being

guilty for the mother’s psychiatric disorder (Kilmes-Dougan and Bolger, 1998). Since OCD

is associated with increased levels of pathological responsibility and guilt (Rachman, 1993;

Salkovskis et al., 1999), being more empathic can lead those individuals to be more

distressed and to present greater severity of depression and anxiety symptoms. For

example, obsessive–compulsive symptoms (e.g., contamination obsessions and avoidant

behaviors) may inhibit the initiative and execution of altruistic actions that would otherwise

be performed by empathic individuals, increasing guilt and depressive feelings. The recent

evidence pointing to the involvement of the sub-genual–septal area in major depression

(Drevets et al., 1998; Mayberg et al., 2005) and in normal social attachment responses

(Bartels and Zeki, 2004; Aron et al., 2005; Moll et al., 2006; Krueger et al., 2007) strongly

support this view.

The levels of personal discomfort, i.e., the emotional response that involves fear of

discomfort from witnessing stressful circumstances or a negative emotional state in other

people, were significantly greater among patients with OCD than among individuals from

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the community. Although the intensity of personal discomfort correlated with all the OCI-R

dimensions, analyses of covariance showed that the BDI and BAI scores explained the

significance of these findings. Indeed, although elevated levels of IRI’s personal discomfort

were seen in different psychiatric disorders, including schizophrenia (Montag et al., 2007);

Asperger syndrome (Rogers et al., 2007); and frontotemporal dementia (Rankin et al.,

2005), analyses of covariance aimed at excluding the role of affective symptoms were not

performed in these studies. Since personal discomfort belongs to the affective dimension of

empathy, we believe that this sort of analyses should be an essential part of these types of

studies. This approach may unveil whether personal discomfort is a primary condition or

secondary to comorbid anxiety and depression.

According to Davis (1983), the IRI fantasy scale taps respondents’ tendencies to

transpose themselves imaginatively into the feelings and actions of fictitious characters in

books, movies, and plays. Unexpectedly, we found a correlation between the fantasy scale

of the IRI and the severity of hoarding behaviors that remained significant after excluding

the effects of the severity of anxiety and depression symptoms. A subsequent stepwise

regression analysis revealed that a model that included severity of depression, anxiety, and

hoarding symptoms predicted 33% of the variance on the fantasy scale (Table5).

In his original study, Davis (1983) found that the fantasy scale was associated with

shyness, loneliness, and social anxiety in males, and with increased ‘‘emotionality” and

verbal fluency in general. Similar neurocognitive results were found by Rankin et al.

(2005), who observed that 25% of the fantasy scale scores where explained by the

phonemic fluency. Davis (1983) suggested that individuals with high scores on the fantasy

scale were uncomfortable in social settings, isolated, emotional, and intelligent. Therefore,

it would be predictable that these patients devote their time and intellectual involvement to

the nonsocial worlds of books, movies, and television – as the content of the fantasy scale

items implies. Indeed, this profile is very similar to the one found in patients with

pathological hoarding in several studies.

For example, Fontenelle et al. (2004) found that patients with OCD and pathological

hoarding presented increased educational levels than regular patients with OCD. From the

neurocognitive point-of-view, Hartl et al. (2004) observed that patients with pathological

hoarding did not exhibit the impaired verbal learning strategies exhibited by patients with

OCD in general. In terms of social aspects, difficulties exhibited by patients with

pathological hoarding were reported in a related study (Soares et al., unpublished thesis)

where 62% of the scores on the SF-36 sub-scores ‘‘social aspects” of patients with OCD

were explained by a model that included the total scores of the IC-R.

It could be argued that shyness, loneliness, and social anxiety in hoarders can be

hardly consistent with increased affective empathic levels, and, as initially predicted,

excessive attachment or increased social bonding. We suggest, however, that the negative

social effects of severe hoarding behaviors may hamper the full expression of increased

empathic abilities that these patients may present.

Admittedly, our study has a number of drawbacks: Firstly, it enrolled a small

number of research subjects. Secondly, the comparison group included medical and

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administrative staff at our research institution, hardly a random control group. Thirdly, our

patients with OCD were under drug and/or cognitive behavioral treatments and it would

have been interesting to compare empathic abilities between those groups. Nevertheless,

since there was a great overlap between patients being treated with drugs (almost 80%) and

patients being treated with cognitive behavior therapy (32%), the small number of patients

being treated exclusively with one or another therapeutic strategy would compromise valid

statistical analyses. It would also be interesting to study OCD patients’ before and after

treatment to check whether their distinctive empathic abilities are ‘‘state” or ‘‘trait”

features. Finally, it must also be stated that the fantasy scale of the IRI have been criticized

for being overly broad (Baron-Cohen and Wheelwright, 2004), including not only aspects

related to cognitive empathy, but also imagination (‘‘I daydream and fantasize, with some

regularity, about things that might happen to me”) and emotional self-control (‘‘In

emergency situations, Ifeel apprehensive and ill at ease”).

In sum, while depression and anxiety explained increased levels of empathic

concern and personal discomfort of patients with OCD, increased levels of fantasy were

especially associated with hoarding behaviors. These findings are consistent with the view

that hoarding constitutes a dimension of OCD that is associated with increased levels of

psychopathology. Given the ever-rising literature on social cognition and the fact that these

new paradigms can help to identify neglected behavioral phenotypes, an approach based on

social neuroscience may provide a fruitful avenue of research to redraw the diagnostic

frontiers of different neuropsychiatric disorders.

Contributors

Find below the list of authors of the manuscript entitled ‘‘Empathy and symptoms

dimensions of patients with obsessive–compulsive disorder” and how they have contributed

to the study.

Drs. Leonardo F. Fontenelle, Isabela D. Soares, Bernard P Range´, and Jorge Moll designed

the study and wrote the protocol. Drs. Isabela D. Soares, Flavia Miele, and Manuela C.

Borges managed the literature searches and analyses. Dr. Ange´licaM. Prazeres undertook

the statistical analysis, and Drs. Leonardo F. Fontenelle and Jorge Moll wrote the first draft

of the manuscript. All authors contributed to and have approved the final manuscript.

Funding

Funding for the manuscript entitled ‘‘Empathy and symptoms dimensions of patients with

obsessive–compulsive disorder” study was provided by the Conselho Nacional de

Desenvolvimento Cientfico e Tecnolgico (CNPq); the CNPq had no further role in study

design; in the collection, analysis and interpretation of data; in the writing of the report; and

in the decision to submit the paper for publication.

Acknowledgement

170

We thank Prof. Ricardo de Oliveira-Souza, who assisted with the discussion of the

manuscript ‘‘Empathy andsymptoms dimensions of patients with obsessive–compulsive

disorder”.

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6.4) CNS Spectr. 2008;13(2):125-130

Case Report

Auditory, Visual, Tactile, Olfactory, and Bodily Hallucinations in Patients with Obsessive-

Compulsive Disorder

Leonardo F. Fontenelle, MD, PhD, Angélica P. Lopes, PhD, Manuela C. Borges,

PhD,Paula G. Pacheco, BS, Antonio L. Nascimento, MD, and Marcio Versiani, MD, PhD

Submitted for publication: August 1, 2007; Accepted for publication: January 15, 2008.

ABSTRACT

Although much attention has been paid to patients who lack insight into their obsessional

beliefs, less importance has been given to individuals with obsessive-compulsive disorder

(OCD) who display perceptual disturbances typically found in psychotic disorders,

including schizophrenia, schizoaffective disorders, or mood disorders with psychotic

features. We would like to call the attention to a phenomenon that has been neglected in the

psychiatric literature: the occurrence of hallucinations and related phenomena in patients

with OCD. In this case report, we describe five clinical vignettes of patients with OCD with

hallucinations in several different sensory modalities, including the auditory, the visual, the

tactile, the olfactory, and the cenesthetic ones. Further psychopathological research should

clarify the clinical significance of hallucinations among patients with OCD.

INTRODUCTION

The relationship between obsessive-compulsive disorder (OCD) and psychosis is an

intricate and complex one. Several reports support the existence of obsessive-compulsive

symptoms in patients with schizophrenia,

1,2

schizoaffective disorders,

and, more rarely,

bipolar disorders.

Bottas and colleagues

have even proposed the creation of a

controversial “schizo-obsessive type” of schizophrenia, distinguished by increased

neuropsychological deficits and poor outcome. On the other hand, a number of other

reports

4-9

have confirmed the existence of patients with OCD who lack insight into their

symptoms, therefore termed “delusional” OCD. To date, it is still unclear whether patients

presenting both psychotic and obsessive-compulsive symptoms, including either

schizophrenia with OCD or OCD without insight, are biologically closer to patients with

OCD and related spectrum disorders

10,11

or to patients with schizophrenia.

Although much attention has been paid to patients who lack insight into their obsessional

beliefs, less importance has been given to individuals with OCD who display perceptual

disturbances typically found in psychotic disorders, including schizophrenia,

schizoaffective disorders, or mood disorders with psychotic features. We would like to call

176

the attention to a phenomenon that has been neglected in the psychiatric literature: the

occurrence of hallucinations and related phenomena in patients with OCD. To reach this

goal, we will present five case vignettes of patients with OCD with disturbances in several

different sensory modalities, including the auditory, the visual, the tactile, the olfactory, and

the cenesthetic ones.

CASE REPORTS

Case 1

Ms. A, a 19-year-old woman with some high-school education, sought treatment at our

clinic in a state of severe anxiety, complaining of “hearing voices.” Approximately 1 year

prior, after reading a book that contrasted “the place and creatures of hell” with “the glories

of heaven,” Ms. A started to hear a voice stating that Satan was her king and that the

demons were going to take her soul. At first, she was hesitant to identify the exact origins

of these “voices”, but soon afterward, after a careful inquiry, she attributed to it an internal

localization. She reported trying to resist and dismiss these voices. Nevertheless, her efforts

proved to be futile. At that time, she had the diagnosis of paranoid schizophrenia and was

taking haloperidol 15 mg/day, levomepromazine 50 mg/day, prometazine 50 mg/day,

biperiden 6 mg/day, and clonazepam 2 mg/day.

During her evaluation, Ms. A described obsessive-compulsive symptoms that began at

12 years of age and included obsessions with aggressive and religious content and check-

ing, washing, counting, and touching compulsions. Although she reported no complaints

between 15 and 18 years of age, the aforementioned obsessive-compulsive symptoms reap-

peared abruptly with the experience of hearing “voices.” According to an evaluation with

the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental

Disorders, Fourth Edition Axis I Disorders (SCID-I), Ms. A presented OCD and major

depressive disorder (MDD). Her initial scores were 31 (severe) on the Yale-Brown

Obsessive-Compulsive Scale (Y-BOCS), 7 (extremely ill) on the Clinical Global

Impressions (CGI) scale, and 50 (severe) on the Beck Depression Inventory (BDI). Ms. A

scored 3 on the insight question of the Y-BOCS (“poor insight”). She had normal physical

and neurological examination, blood tests, and urine analysis. Her family history was

unremarkable, with the exception of her mother, who had presented a hypomanic episode

induced by antidepressants in the past. Ms. A was treated with clomipramine up to 150

mg/day, thioridazine 50 mg/day, and clonazepam 2 mg/day. At week 4, her scores on the

Y-BOCS dropped >50% and her CGI was 3 (mildly ill). Although a hypomanic episode

prompted the reduction of clomipramine to 75 mg/day, her scores on the Y-BOCS and CGI

have remained stable since then.

Case 2

Ms. B, a 34-year-old white unemployed woman with some superior education, presented

to treatment complaining of black dots in her hands, which she argued to be pieces of her

own feces. Neither the examiner nor the family members were able to visualize the dots,

but the patient remained convinced that they existed and consisted of small pieces of feces

glued to her hands. These dots led Ms. B to engage in impairing washing compulsions. In

fact, Ms. B had an almost 20-year history of severe and unremitting obsessive-compulsive

symptoms, including obsessions with contamination, aggressive, symmetry, and somatic

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themes; avoidant behaviors resulting in clutter of several “contaminated” objects

(especially clothes); and washing, checking, hoarding and miscellaneous compulsions.

Besides OCD, Ms. B was found to display comorbid bipolar II disorder, most recent epi-

sode depressed, according to an evaluation with the SCID-I. Her initial scores were 35 on

the Y-BOCS (extreme), 7 (extremely ill) on the CGI, and 31 on the BDI (severe). Ms. B

scored 4 on the insight question of the Y-BOCS (“lacks insight”). She had normal physical

and neurological examination, blood tests, and urine analysis. Ms. B was prescribed

venlafaxine 75 mg/day but dropped-out of treatment after 2 weeks. After 3 years in a drug-

free state, she presented to treatment again. At the second evaluation, Ms. B’s main concern

was rigorously the same, just like her scores obtained on the first assessment. She ceased

treatment again soon afterward.

Case 3

Ms. C, a 19-year-old white woman with some high-school education, reported being

afraid of losing bladder control. She described feeling drops of urine running down her legs

even hours after regular micturition. Ms. C recognized the phenomenon as senseless, but

reported that the tactile sensation of “urine” was too anxiogenic to be dismissed. Ms. C felt

compelled to bathe herself and to employ separate sets of towels to get her arms and legs

dry. Since 7 years of age, she reported being haunted by contamination obsessions centered

on the possibility of having contact with the urine of domestic animals on street pavements.

She displayed severe avoidant behaviors, being house-bound most of her adolescence and

avoiding walking close to street poles and using sandals to prevent contamination. She also

reported significant aggressive and religious obsessions and checking, counting, and mental

compulsions.

According to an evaluation with the SCID-I, Ms. C presented OCD and comorbid MDD

and binge eating disorder. Her initial scores were 30 on the Y-BOCS (severe) and 6 on the

CGI (severely ill). She scored 2 on the insight question of the Y-BOCS (“fair insight”). Ms.

C had normal physical and neurological examination, blood tests, and urine analysis. Her

family history was unremarkable, with the exception of an uncle, who was reported to have

OCD. Ms. C was treated with several different drug regimens, employed for adequate

periods and with optimal dosages, including different selective serotonin reuptake

inhibitors (ie, fluoxetine 60 mg/day, citalopram 60 mg/day, and escitalopram 40 mg/day)

and venlafaxine 225 mg/day augmented with risperidone 2 mg/day, quetiapine 100 mg/day,

clomipramine 75 mg/day, and reboxetine 8 mg/day. Despite these strategies, employed in

association with cognitive-behavioral therapy, Ms. C reported no significant improvement

of her symptoms.

Case 4

Ms. D, a 28-year-old white journalist, complained of a fear of “being stuck with an

HIV contaminated needle.” This fear made her avoiding crowded or public places and

objects that could hide infected needles, including bags and chairs with fluffy covers. Ms.

D reported that she feels twinges all over her body whenever she faces challenging

situations, such as leaving home or walking in a crowded place. She states that, during

these activities, the experience of twinges is associated with the conviction of being pricked

by a contaminated needle. After those moments, however, she acknowledges the absurdity

of her beliefs.

178

Since 14 years of age, she displayed obsessions with aggressive and contamination content,

and checking, ordering and symmetry compulsions. In fact, she reported being more

severely ill in the past, to the point of being completely house-bound. At that time, the

stitches were more “painful” and the conviction of being stuck by infected needles was

more persistent. According to an evaluation with the SCID-I, Ms. D was found to display

OCD and a current MDD. She had normal physical and neurological examination, blood

tests, and urine analysis. Ms. D reported being treated with several different selective

serotonin reuptake inhibitors in the past, and improved partially on fluoxetine 60 mg/day

and clonazepam 2 mg/day. At the time of her assessment in our service, her initial scores

were 24 on the Y-BOCS (severe), 5 on the CGI (markedly ill), and 17 on the BDI

(moderate depression). She scored 2 on the insight question of the Y-BOCS (“fair insight”).

Case 5

Mr. E, a 25-year-old unemployed black man with some high-school education, was

admitted to our inpatient ward for bathing relentlessly despite water leaking in his

neighbors’ apartments. He insisted that, since 20 years of age, several parts of his body,

including his feet, elbows, back, and face, persistently exhaled a fetid odor. Mr. E described

feeling ashamed and, in an attempt to get rid of this disgusting odor, bathed compulsively

and employed increased amounts of deodorants, perfumes, and other personal-hygiene

products.

Mr. E denied other significant obsessive-compulsive symptoms. According to an

evaluation with the SCID-I, Mr. E main psychiatric condition could be double-coded as

OCD with poor insight or delusional disorder not otherwise specified, along with comorbid

dysthymic disorder. An alternative diagnosis for Mr. E condition was olfactory reference

syndrome, a diagnosis proposed by Pryse-Phillips

and considered part of the obsessive-

compulsive spectrum.

His initial scores were 32 on the Y-BOCS (extreme) and 7 on the

CGI (extremely ill). He scored 4 on the insight question of the Y-BOCS (“lacks insight,

delusional”). Mr. E had normal blood tests, urine analysis, and neurological and physical

examination, except for an abrasion in his left foot caused by excessive washing and

rubbing. Mr. E’s family history was unremarkable for psychiatric disorders. During his

hospital stay, clomipramine 25 mg/day was added to the treatment regimen. Unfortunately,

Mr. E’s family requested discharge after only a few days of hospital admission, even before

his drug dosages could be adjusted. He never returned for treatment.

DISCUSSION

The presence of different types of perceptual disturbances in OCD patients has been

widely acknowledged. For example, Miguel and colleagues

have proposed the general

term “sensory phenomena” to describe a plethora of symptoms among patients with OCD

and/or Tourette syndrome, some resembling those described in our report. The symptoms

previously identified by Miguel and colleagues

included uncomfortable sensations in the

skin, muscles, and joints or body sensations that come before or along with some of the

repetitive behaviors. The difference between our patients’ complaints and the ones reported

in these previous studies is the hallucinatory character of former phenomena.

Although the concept of hallucination has varied throughout history and, according to

different psychiatric schools,

its most commonly accepted definition is that of a false

sensory perception occurring in the absence of any relevant external stimulation of the

179

sensory modality involved.

Accordingly, our patients described hearing voices, seeing

dots of feces in their hands, feeling drops of urine in their legs, sensing twinges of infected

needles all over the body, or smelling fetid odors. Nevertheless, whether the phenomena

reported by our patients are true or pseudo-hallucinations is a matter for debate.

A true hallucination has been defined as a realistic experience (ie, one that is corporeal

and assigned to the outside space) associated with impaired reality testing. Much more con-

troversial, though, is the concept of pseudo-hallucination.

16,18

For example, Taylor

termed

“imagined” pseudo-hallucination the phenomenon that involves an internal and non-

corporeal experience and “perceived” pseudo-hallucination the experience that, despite

being assigned to external space and corporeal, is associated with preserved reality testing.

According to these definitions, our patients’ perceptual complaints may be best described

as auditory “imagined” pseudo-hallucinations (Case 1), “perceived” tactile (Case 3) and

bodily (Case 4) pseudo-hallucinations, visual (Case 2), and olfactory (Case 5) “true”

hallucinations. However, these concepts may be difficult to employ in clinical practice

since the patients may be uncertain regarding the origins of their experiences

; there is a

fluid transition between hallucinations and other modes of perception

; and reality testing

may fluctuate in OCD depending on whether the patient is being exposed to an anxiogenic

stimuli.

Although the clinical utility of differentiating true from pseudo-hallucinations is

still contentious,

the aforementioned criteria suggest that our patients’ complaints encom-

pass the whole spectrum of hallucinatory phenomena. Therefore, we prefer to use the term

“hallucination”

in a broad sense to portray the experiences described by our patients.

Since some of our patients had severe depression, the role played by mood disorders on

the development of auditory and visual hallucinations by patients with OCD need to be

taken into consideration. Insel and Akiskal

had already reported a shift from an obsession

to a delusion when a disturbed affective process leads to the abandonment of resistance (the

internal struggle against an obsessive urge or idea) and loss of insight. We feel that a

similar understanding may be applied to some obsessions that develop into psychologically

“understandable” hallucinations in the presence of a major depressive episode or an

anxiogenic and challenging situation.

Unfortunately, the discrimination between obsessions and hallucinations may not be

easy,

22,23

especially when they present musical qualities.

24-27

This is not surprising, since

both obsessions and hallucinations

have been shown to reflect impaired intentional

cognitive inhibition, while context memory abilities was found to be preserved in the

former and impaired in the latter group.

27,28

In a recent review, van der Zwaard and Polak

provided some guidelines deemed relevant for disentangling obsessions from

hallucinations. According to them, obsessions are usually associated with preserved reality

testing and do not regularly display tactile, olfactory, and gustatory qualities, many of

which were present among our patients’ complaints.

The fact that patients with OCD may exhibit hallucination-related phenomena suggests

that hey can share with psychotic disorders dysfunctional dopaminergic circuits.

Accordingly, the results from several clinical and preclinical studies

are consistent with

an increased midbrain dopaminergic neurotransmission in OCD. Additionally, more

similarities than differences emerge when one examines the functional-circuit theories in

OCD and, for example, schizophrenia.

It is generally recognized that a group of parallel cortico-subcortical circuits, each

including discrete areas of the prefrontal cortex (ie, the dorsolateral prefrontal cortex, the

lateral orbital cortex, and the anterior cingulate cortex), are central to the pathophysiology

180

of some psychiatric disorders. For example, while a dysfunctional dorsolateral prefrontal

cortex circuit has been described as central to schizophrenia, an abnormal activity of the

lateral orbital cortex and the anterior cingulate cortex) circuits has been implicated in

OCD.

Clearly, these circuits share several anatomic substrates, including the frontal lobes,

striatum, globus pallidus, and thalamus.

If one accepts that there is an element of open circuitry, thus allowing connections

between the various substructures of the previously mentioned circuits (ie, the nuclei of the

thalamus) then one could argue that the circuits described for OCD and schizophrenia are

very much the same, raising the possibility that a common functional aberration can lead to

the co-expression of what seem to be completely different symptoms.

Alternatively, the identification of hallucinations of different sensory modalities in our

patients with OCD may reflect the involvement of specific brain systems that are not

regularly dysfunctional in ordinary patients, including temporal (Cases 1 and 5), occipital

(Case 2), and somethesic areas (Cases 3 and 4). For example, Zungu-Dirwayi and

colleagues

described temporal lobe dysfunctions among patients presenting obsessions of

with a musical or acoustical character. It is unclear how the presence of these features may

impact on treatment response. Nevertheless, we speculate that hallucinations among

patients with OCD may serve as a proxy for increased dopaminergic activity and the

requirement of dopamine receptors blockers. It must be stated, however, that we were

unable to test this hypothesis, since data on treatment response was not gathered in a

systematic way.

CONCLUSION

Although there is a growing literature on the clinical and biological aspects of

patients with OCD who lack insight into their symptoms (therefore termed “delusional”),

patients with OCD may also display perceptual disturbances typically found in psychotic

disorders, including schizophrenia, schizoaffective disorders, or mood disorders with

psychotic features. We argue that these symptoms can include hallucinations and other

related phenomena and may be associated with different degrees of insight. These

experiences may involve different sensory modalities, including the auditory, the visual, the

tactile, the olfactory, and the cenesthetic modalities.

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6.5) BIOL PSYCHIATRY 2008;63:1S-301S

522. Social Cognition and Symptoms Dimensions of Patients with Obsessive-Compulsive

Disorder

Leonardo F. Fontenelle

1,2

, Isabela D. Soares

, Flavia Miele

, Bernard P. Rangé

, Angélica

M. Prazeres

, Manuela C. Borges

, Jorge Moll

Anxiety and Depression Research Program, Institute of Psychiatry, Federal University of

Rio de Janeiro, Rio de Janeiro, Brazil,

Department of Psychiatry and Mental Health,

Institute of Community Health, Fluminense Federal University, Niterói, Brazil,

Postgraduate Program in Psychology, Institute of Psychology, Federal University of Rio

de Janeiro, Rio de Janeiro, Brazil,

Brain Morphometry and Investigative Neuroimaging,

LABS-D’Or Hospital Network, Rio de Janeiro, Brazil

Background:

Social cognitive neuroscience has highlighted the importance of the temporal

cortex, the amygdala and the prefrontal cortex for empathic abilities. The aim of this study

is to describe the relationship between empathy, evaluated with the Interpersonal Reactivity

Index (IRI), and symptom dimensions of patients with OCD, a neuropsychiatric disorder

thought to involve fronto-subcortical dysfunction.

Methods:

We evaluated 53 patients with OCD and 53 age- and sex-matched individuals

from the community with the Structured Clinical Interview for the Diagnosis of DSM-IV

(SCID), the Saving Inventory-Revised (SI-R), the IRI the Obsessive-Compulsive

Inventory-Revised (OCI-R), the Beck Depression Inventory (BDI), and the Beck Anxiety

Inventory (BAI).

Results:

Patients with OCD displayed greater levels of affective empathy [i.e. empathic

concern (p=0.006) and personal distress (p<0.001)] than community controls. In bivariate

analyses, the severity of hoarding symptoms of patients with OCD correlated with empathic

concern (r=0.39; p <0.001), fantasy (r=0.36; p<0.01), and personal distress (r=0.39;

p<0.001). In partial correlation analyses adjusting for comorbid depression and anxiety,

only the association between hoarding and fantasy remained robust (r=0.41; p<0.001).

Conclusions:

Our findings suggest that hoarding is linked to specific aspects of

interpersonal reactivity. Nevertheless, the severity of comorbid psychiatric symptoms

seems to be the main determinant of the distinctive pattern of empathic abilities exhibited

by patients with OCD.

Supported by Conselho Nacional de Desenvolvimento Cientifico e Tecnológico

183

6.6) BIOL PSYCHIATRY 2008;63:1S-301S

541. The Impact of Hoarding on the Quality of Life of Patients with Obsessive-Compulsive

Disorder

Isabela D. Soares

, Flavia Miele

, Bernard P. Rangé

, Manuela C. Borges

, Angélica M.

Prazeres

, Leonardo F. Fontenelle

2,3

Postgraduate Program in Psychology, Institute of Psychology, Federal University of Rio

de Janeiro, Rio de Janeiro, Brazil,

Anxiety and Depression Research Program, Institute of

Psychiatry, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil,

Department of

Psychiatry and Mental Health, Institute of Community Health,

Fluminense Federal University, Niterói, Brazil

Background:

There is increasing evidence that hoarding may constitute a discrete

syndrome with specific clinical and neurobiological features. The aim of this study is to

evaluate the distinctive impact of hoarding and other obsessive-compulsive symptoms

dimensions on different aspects of the quality of life of patients with obsessive-compulsive

disorder (OCD).

Methods:

We evaluated 53 patients with OCD and 53 age- and sex-matched individuals

from the community with a socio-demographic questionnaire, the Structured Clinical

Interview for the Diagnosis of DSM-IV, the Short-Form Health Survey-36 (SF-36), the

Saving Inventory-Revised, the Obsessive-Compulsive Inventory-Revised, the Beck

Depression Inventory, and the Beck Anxiety Inventory. A series of stepwise linear

regression analyses were performed with the SF-36 dimensions as dependent variables and

the sociodemographic and clinical features as independent ones.

Results:

Patients with OCD displayed significantly lower levels of quality of life in all

dimensions measured by the SF-36, with the exception of pain. A model that included

hoarding, depressive symptoms, and employment status predicted 62% of the variance of

the social aspects of OCD patients’ quality of life. Further, a series of models that included

depressive, but not obsessive-compulsive symptoms, explained the variance of all but one

SF-36 dimension (i.e. limitation due to physical aspects).

Conclusions:

Our findings suggest that hoarding is linked to a different pattern of quality

of life among patients with OCD and that the severity of comorbid psychiatric symptoms,

but not of OCD itself, explains the impairment in most aspects of the quality of life of

patients with OCD.

Supported by Conselho Nacional de Desenvolvimento Cientifico e Tecnológico

184

6.7) Psychiatry Research, 2009 (no prelo)

Quality of life and symptoms dimensions of patients with obsessive-compulsive disorder

Isabela S. Fontenelle

a,b

, Leonardo F. Fontenelle

a,c

, Manuela C. Borges

, Angélica M.

Prazeres

, Bernard P. Rangé

, Mauro V. Mendlowicz

, Marcio Versiani

Anxiety and Depression Research Program, Institute of Psychiatry, Universidade Federal do Rio de Janeiro

(IPUB/UFRJ), Rio de Janeiro, Brazil

Postgraduate Program in Psychology, Institute of Psychology, Universidade Federal do Rio de Janeiro

(IP/UFRJ), Rio de Janeiro, Brazil

Department of Psychiatry and Mental Health, Institute of Community Health, Universidade Federal

Fluminense (MSM/UFF), Niterói, Brazil

Received 18 November 2008

Received in revised form 24 March 2009

Accepted 15 April 2009

Available online xxxx

Keywords:Hoarding; Obsessive-compulsive disorder; Quality of life; Depression; Beck

Depression Inventory

The aim of this study was to evaluate the impact of different dimensions of obsessive-

compulsive symptoms, of comorbid anxious depressive ymptoms, and of sociodemographic

characteristics on the quality of life of patients with obsessive-compulsive disorder (OCD).

We evaluated patients53 patients with OCD and 53 age and gender matched individuals

from the community with a socio demographic questionnaire, the Structured Clinical

Interview for the Diagnosis of DSM-IV, the Short Form Health Survey (SF-36), the Saving

Inventory Revised, the Obsessive-Compulsive Inventory Revised, the Beck Depression

Inventory, and the Beck Anxiety Inventory. A series of stepwise linear regression analyses

were performed, having the SF 36 dimensions as the dependent variables and the socio

demographic and clinical features as the independent ones. Patients with OCD displayed

significantly lower levels of quality of life in all dimensions measured by the SF 36, except

bodily pain. A model that included depressive symptoms, hoarding, and employment status

predicted 62% of the variance of the social functioning dimension of the quality of life of

patients with OCD. Washing symptoms explained 31% of the variance of limitation due to

physical health problems. Further, a series of models that included depressive, but not

obsessive compulsive symptoms, explained the remaining SF 36 dimensions. The severity

of depressive and anxiety symptoms seems, therefore, to be powerful determinants of the

level of quality of life in patients with OCD.

185

1. Introduction

Only a small number of studies have assessed the relationship between quality of

life and different dimensions of patients with obsessive- compulsive disorder (OCD)

(Stengler-Wenzke Q2 , 2007). Among those who did it, most have evaluated patients with

predominantly obsessive, predominantly compulsive, or mixed symptoms. For instance,

Masellis et al. (2003) found that quality of life was particularly affected by obsessions, but

not by compulsions. They also reported that comorbid depression severity was the single

greatest predictor of poor quality of life among patients with OCD. In the study by Moritz

et al. (2005), a strong association was found 55 between self-assessed or clinician-rated

depression and the scores of the mental health, social functioning, role emotional, and

vitality subscales of the Medical Outcomes Study 36-Item Short-Form healthy Survey (SF-

36). Severity and the number of obsessions were most strongly associated with the role-

emotional and mental health components, whereas the number of compulsions showed a

relatively uniform pattern of correlations with the SF- 36 subscales.

Similarly, Eisen et al. (2006) found that marital status and the severity of depressive

and obsessive (but not compulsive) symptomswas significantly associated with the Quality

of Life Enjoyment and Satisfaction Questionnaire (Q- LES-Q) scores and accounted for

42% oftheir variance. In the same vein, Rodriguez- Salgado et al. (2006) found that the

severity of the obsessive and of depressive symptoms correlated with all SF- 36 subscales,

while compulsive symptoms subscale was associated only with the social functioning,

emotional role, mental health and vitality subscales.

Finally, in the study by Stengler- Wenzke et al. (2007), compulsions were

associated with reduced scores in theWorld Health Organization Quality of Life Brief

Version (WHOQOL-BREF) ‘physical well-being’,‘psychological well-being’ and

‘environment’ domains, whereas obsessions had no significant impact on quality of life at

all. However, in this study, depressive symptoms were found to be strong predictor of poor

quality of life in OCD patients.

In some studies, patients with OCD reported levels of quality of life that are lower

than those exhibited by individuals with chronic and disabling conditions, such as

schizophrenia (Moritz, 2008). Often, treatment for OCD is started only after the disorder

has progressed significantly and important personal and social resources (e.g., social

support and employment) have already been severly compromised (Moritz, 2008). As

reported above, the reasons for the low quality of life in OCD are probably

multidimensional and may vary largely across studies (Moritz, 2008).

While comorbid depression seems to play a definite role in the impairment of

quality of life seen in OCD (Masellis et al., 2003; Moritz et al., 2005; Eisen et al., 2006;

Rodriguez-Salgado et al., 2006; Stengler-Wenzke et al., 2007; Niederauer et al., 2007), it is

still unclear whether quality of life is more affected by obsessions, by compulsions, or by

both equally. Indeed, for the purpose of studying the pathophysiology of OCD, splitting

this disorder into predominantly obsessive, compulsive, or mixed subtypes did not turn out

to be as fruitful as previously expected. Although it is unquestionable that OCD is a

phenomenologically homogeneous disorder), there is tremendous variation in its symptoms

content. For example, in a recent review paper reporting on twelve principal-components

and confirmatory factor analytic studies and involving more than 2000 patients with OCD,

at least four symptom content dimensions were consistently extracted: symmetry/ordering,

contamination/cleaning, obsessions/checking, and hoarding (Mataix-Cols et al., 2005).

186

The so-called “compulsive hoarding syndrome” in OCD is associated with

distinctive features, including earlier age at onset (Samuels et al., 2002; Fontenelle et al.,

2004), worse global functioning (Saxena et al., 2002; Wheaton et al., 2008), greater levels

of disability (Frost et al., 2000; Lochner et al., 2005), poor insight into symptoms

(Damecour and Charron, 1998; Storch et al., 2007), more frequent reports of traumatic

events in the past (Hartl et al., 2005; LaSalle-Ricci et al., 2006), greater occurrence of

certain types of OCD symptoms (e.g. symmetry/ordering) and comorbid axis I and II

disorders (Frost et al., 2000; Samuels et al., 2002; Fontenelle et al., 2004; Lochner et al.,

2005; Hasler et al., 2005; LaSalle-Ricci et al., 2006), stronger association with certain

genotypes (Lochner et al., 2005; Samuels et al., 2007a,b), heavier genetic load (Hasler et

al., 2007) and higher prevalence of hoarding behavior among first-degree relatives

(Samuels et al., 2006), characteristic neuroanatomical (Saxena et al., 2004) and

neuropsychological (Lawrence et al., 2006) markers, putative dopaminergic involvement

(Stein et al., 1999), and inadequate response to treatment with serotonin-reuptake inhibi

tors (Black et al., 1998; Winsberg et al., 1999; Mataix-Cols et al., 1999), with cognitive

behavioral-therapy (Mataix-Cols et al., 2002), or with their combination (Frost et al., 2000).

The objectives of this study were three fold: (1) to compare patients with OCD and

individuals from the community in terms of quality of life, as assessed by the SF-36, (2) to

evaluate the relationship between the severity of different OCD dimensions [measured by

the Obsessive–Compulsive Inventory–Revised (OCI–R; Souza et al., 2008) and by the

Saving Inventory–Revised (SI–R; Soares et al., 2007)] with the levels of quality of life of

patients with OCD, and (3) to investigate whether sociodemographic factors and comorbid

depressive and anxious symptoms [measured by the Beck Depression and Anxiety

Inventories (BDI and BAI; Cunha, 2001) play any role in the impairment of quality of life

of patients with OCD. Since hoarding is emerging as the most distinctive OCD subtype

(Mataix-Cols et al.,2005), with unique biological and clinical features, we predicted that

individuals with more significant hoarding symptoms would be associated with a pervasive

pattern of impairment in the physical, mental, and social aspects of quality of life.

2. Methods

Volunteers for this study were consecutively recruited among patients undergoing

treatment in the (1) Anxiety and Depression Research Program at the Institute of Psychiatry

of the Universidade Federal do Rio de Janeiro (IPUB/UFRJ), the (2) Division of Applied

Psychology at the Institute of Psychology of the same university (DPA/UFRJ), and (3) the

first author's private practice. The inclusion criteria were (1) the diagnosis of OCD, with or

without psychiatric comorbidity confirmed by means of the Structured Clinical Interview

for DSM-IV Axis I disorders (SCID-IV) (Del-Ben et al., 2001), (2) age between 18 and 80

years, and (3) absence of any other neurological, endocrinological, or systemic disorder that

could interfere with the interpretation of the results. In the presence of any psychiatric

comorbidity, only patientswho developed OCD as a primary disorder, either in terms of

chronology or in terms of severity of symptoms, were included. Regarding the patients with

OCD, 47 (72.3%) were recruited in the Anxiety and Depression Research Program of the

IPUB/UFRJ, 10 (15.4%) in the Division of Applied Psychology of the IP/UFRJ, and 8

(12.3%) fromthe first author's private practice. Since patients in different stages of

treatment were invited to participate in our study, the severity of the obsessive–compulsive

187

symptoms varied largely. We believe, however, that this feature has provided our sample

with a desirable degree of heterogeneity.

The control group consisted of community members recruited through local

advertisements and included medical and administrative staff of the Universidade Federal

do Rio de Janeiro. Inclusion criteria for the control group were (1) age between 18 and 80

years, and (2) absence of any other neurological, endocrinological, or systemic disorder that

could interfere with the interpretation of our results. Controls were not screened beforehand

for the presence of psychiatric disorders, since we intended to avoid the selection of a

“supernormal” sample, which would be not representative of the general population.

2.1. Procedures

The local Institutional Review Board approved this research protocol and all

participants signed an informed consent after receiving a detailed explanation on the

procedures and risks involved in the study. Patients with OCD, but not controls, were

evaluated with the Brazilian version of the SCID-IV (Del-Ben et al., 2001). The SCID-IV is

a semistructured clinical interview to be administered by clinicians in order to diagnose

Axis Imental disorders according to the DSM-IV criteria. The inter-rater reliability of the

Brazilian Portuguese version of SCID-IV was deemed to be at least satisfactory for mood

disorders (

=0,87); psychotic disorders (

= 0,90); substance related disorders(

= 0,76);

anxiety disorders (

=0,61); and the specific diagnostic categories.

Since two different centers (IPUB/UFRJ and IP/UFRJ) were responsible for the

recruitment and administration of the SCID in the majority of cases, questions could be

raised over the reliability of the methods employed. However, two expert diagnosticians

with a doctoral degree and extensive experience in the assessment and treatment of patients

with OCD (ISF and LFF) reviewed all case materials and assigned final best-estimate

diagnoses. Ten cases presenting difficult differential diagnoses had their Axis I disorders

diagnoses confirmed at the consensus conferences.

Patients and controls were asked to fill out a sociodemographic questionnaire

probing issues like age, gender, educational level, marital and employment status, and

monthly income. A clinical questionnaire was employed to collect data on the age at onset

of subclinical obsessions and/or compulsions (i.e. the age at which the patient first

remembers presenting obsessive–compulsive symptoms, even those not accompanied by

significant feelings of distress or impairment), psychiatric comorbidities (according to the

SCID-I), and previous and current therapeutic strategies.

2.2. Instruments

2.2.1. Saving Inventory –Revised (SI–R)

The SI– R was developed by Frost et al. (2004) to evaluate the severity of hoarding

behaviors in clinical and non-clinical populations. It is a self-administered Likert-type scale

containing 23 items that are divided into three subscales: hoarding (9 items), difficult

discarding (7 items) and acquisition (7 items). The Brazilian version of the SI– R exhibited

excellent internal consistence (Cronbach's alpha=0.94 in patients with OCD and 0.84 in

community individuals), excellent to good test– retest reliability (r=0.94 in patients with

OCD and r= 0.59 in community individuals), and moderate to good convergent validity

188

with the hoarding dimension of the Obsessive– Compulsive Inventory–Revised (Soares et

al., 2007), i.e. r=0.55 in community individuals and r= 0.88 in patients with OCD.

2.2.2. Beck Depression Inventory (BDI)

The BDI is the most widely used self-rated instruments for evaluating the severity

of depressive symptoms in clinical and nonclinical samples. The scale has 21 items, each

one consisting of four statements describing increasing intensities of symptoms of

depression. Items are rated on a scale from 0–3, reflecting how participants have felt over

the past week. Possible scores range from0– 48, with higher scores reflecting more severe

depressive symptoms. The Brazilian Portuguese version of the BDI has adequate

psychometric properties, including at least satisfactory internal consistency (Cronbach's

alpha=0.82); construct validity (r= 0.65), and test–retest reliability (r=0.86)(Cunha, 2001).

2.2.3. Beck Anxiety Inventory (BAI)

The BAI is a self- report instrument designed to measure the severity of anxiety.

The scale has 21 items describing subjective, somatic, or panic-related symptoms. Items are

rated on a scale from 0–3, reflecting how participants have felt over the past week. Possible

scores range from 0– 63, with higher scores reflecting more severe anxiety symptoms. The

Brazilian Portuguese version of the BAI has satisfactory psychometric properties, including

good to excellent internal consistency (Cronbach's alpha=0.83), convergent validity [with

the State (r= 0.76)-Trait (r=0.78) Anxiety Inventory], and test–retest reliability (r=0.99)

(Cunha, 2001).

2.2.4. Obsessive–Compulsive Inventory–Revised (OCI–R)

The OCI–R (Foa et al., 2002) is the shorter, revised version of the Obsessive–

Compulsive Inventory (OCI), an instrument that evaluates the severity of a series of

obsessive–compulsive symptoms (Foa et al., 1998). The OCI–R is a self-administered

Likert-type scale that contains 18 items and provides a total score and six subscale scores:

washing, checking, ordering, rumination, hoarding, and neutralization.

The Brazilian Portuguese version of the OCI–R exhibited excellent internal

consistency (0.94) and test–retest reliability (0.98). It also showed moderate convergent

validity with the Yale–Brown Obsessive–Compulsive Scale nt (0.47) (Souza et al., 2007).

2.2.5. Medical outcomes study 36-item short-form health survey (SF-36)

The SF-36 (Ware and Sherbourne, 1992) is the most commonly used measure of

quality of life and has been amply employed in studies of diverse medical and psychiatric

conditions. The SF-36 is generic and multidimensional and, since its use is not restricted to

specific age ranges or types of patients, allows comparisons among different disorders and

treatments.

The scale is composed of 36 items and captures 8 major domains of quality of life:

physical functioning, limitations due to physical health problem, bodily pain, general

health, vitality, social functioning, limitations due to emotional problems (role-emotional),

and mental health. The raw scores for each of the 8 subscales span from 0 to 100, with 0

representing the worst and 100 representing the best possible quality of life status. General

health, vitality, and mental health subscales differ from the other five in that they are

“bipolar” (i.e., a score of 100 in one of them does not denote a mere absence of problems

but implies the existence of positive health states such as happiness or well-being).

189

In Ciconelli et al.'s (1997) validation study of the Brazilian Portuguese version of

the SF-36, inter-rater and test–retest reliability for the eight subscales ranged from 0.55 to

0.81 and 0.44 to 0.84, respectively. Acceptable levels of convergent validity were found

between comparable dimensions of the SF-36, of the Health Assessment Questionnaire, and

of the Nottingham Health Profile. The Brazilian Portuguese version of the SF-36 exhibited

satisfactory Cronbach's alpha coefficients for seven out of the eight dimensions of the SF-

36 (the only exception being the General Health Perception dimension, with a Cronbach's

alpha of 0.60) (Saccomann et al., 2007).

2.3. Statistical analyses

Comparisons of categorical variables were done by means of the chi-square test.

Continuous variables were compared using the independent Student's t test or the Mann–

Whitney test, depending on the normality of data distribution. Stepwise linear regression

analyses were employed to explore the relationship between a series of variables (including

current age,marital status, employment status, washing, checking, ordering, obsession, and

neutralization dimensions of the OCI– R, different SI–R dimensions, the BDI and the BAI)

and each of the SF- 36 dimensions. Given its colinearity with other OCI– R subscores, we

decided not to include the total OCI–R score in the regression analyses. All analyses were

performed bymeans of the SPSS statistical software (SPSS 10 for Windows, SPSS,

Chicago, IL, USA). The statistical level of significance chosen was 5%.

3. Results

We recruited a total of 135 participants who fulfilled the inclusion criteria: 65

patients with OCD and 70 community individuals. The volunteers were predominantly

female (n=82; 60.7%) with a mean age of 37.3 (±13.5) years. Sixty- nine (51.1%)

participants were single, 48 (35.6%) were married, 7 (5.2%) were divorced, 6 (4.4%) were

separated and 5 (3.7%) were widowed. The volunteers had on average 13.2±4.1 years of

formal education and 78 (57.8%) were currently employed. Their mean monthly income

was 2.120 (±2.172) reais (about 1.100 US dollars). A comparison between the socio-

demographic characteristics of patients with OCD and individuals from the community is

depicted in Table 1.

190

Although we believe it would be worthwhile to contrast the characteristics of

patients and volunteers recruited in different centers, small numbers precluded valid

comparisons. In general lines, however, they were deemed quite similar from the socio-

demographic and clinical points of view.

Patients with OCD reported the onset of obsessions and compulsions at age

14.5±10.5 and 15.9±12.7 (years ± standard deviation), respectively. Regarding comorbid

disorders, 35.9% of the patients with OCD exhibited a current major depressive episode,

6.3% had social phobia, and 6.3% presented a dysthimic disorder. Most patients were

already undergoing psychological and/or pharmacological treatment. For example, 79.7%

of patients were being medicated with a serotonin reuptake inhibitor, 40% with a

benzodiazepine, and 32.3% with an antipsychotic. Further, 32.3% of the patients were

being treated with cognitive-behavioral therapy.

191

Patients with OCD and community controls were matched on the basis of age and

gender, creating two groups with 53 participants each. Patients with OCD presented greater

severity of depressive symptoms (according to the BDI) and of anxiety symptoms

(according to the BAI) (see Table 1). Further, they had a lower quality of life than

community controls in all but one dimension of the SF- 36, bodily pain, where only a trend

toward significance was found (see Table 2).

The eight SF-36 subscaleswere entered as dependent variables in a series of

multiple stepwise linear regression analyses conducted with the whole sample of patients

with OCD (n=65). Several relevant sociodemographic and clinical attributes were entered

as independent variables, including the patients'current age, marital status, employment

status, and the BDI, BAI, OCI–R subscales, and SI–R scores. The results generated by

these analyses and the models that explained the most variance for each of the SF-36

dimensions are depicted in Table 3.

192

4. Discussion

As noted above, OCD is a multidimensional mental disorder, encompassing a large

variety of forms of presentation, putative neurobiological substrates and possible treatment

outcomes. The objective of this studywas to evaluatewhether different OCD symptom

dimensions were associated with impairment in distinctive aspects of the quality of life.

Our results support the initial hypotheses only partially: as we expected, hoarding and

washing symptoms accounted significantly for the decline in particular aspects of our

patients'quality of life, but comorbid symptoms, especially depressive and anxiety ones,

remained themost significant predictors of the impairment of quality of life of subjects with

OCD. These findings, which have been reported in other studies (Masellis et al., 2003;

Moritz et al., 2005; and Strenger-Wenzke et al., 2006), seems to imply that treating

depression and anxiety symptoms in OCD might be a critical step toward restoring quality

of life and well-being in these patients.

The SF-36 social functioning subscale evaluates how much impaired physical or

emotional health interferes in the social activities involving family, neighbors or friends. In

our study, a model that included the severity of depressive and hoarding symptoms and the

employment status of our patients with OCD explained 62% of the variance of this

subscale. Besides the well-known and somewhat obvious impact of depression and

unemployment status on the quality of life of patients with OCD, the role of hoarding

193

symptoms in the impairment of social functioning- related aspects of quality of life

deserves some additional comments. It is conceivable that hoarding of “rubbish” may

exhert negative effects through several mechanisms: (1) affecting the family members'

sense of comfort, (2) limiting the utilization of dwelling space, (3) interfering in the

relationship with neighbors due to sanitary problems (such as excessive dust, insects, or

malodorous environments) or to an increased risk of fire accidents, and (4) restricting visits

from relatives or friends due to feelings of shame and embarassment. All these factorsmay

contribute to increase stigmatization and social isolation, and, ultimately, lead to the

reduced social quality of life observed in OCD hoarders.

A study conducted in a service that provides assistance to the elderly of a North-

American community found that the majority of individuals with pathological hoarding

were single, separated or widowed women living by themselves (Kim et al., 2001).

Individuals who were never married presented more severe hoarding symptoms, which

were associated with increased levels of dysfunction and with less than satisfactory

response to general intervention measures (Kimet al., 2001). Further, the severity of

hoarding was found to correlate with the severity of social anxiety in a sample of US

college students (Coles et al., 2003). On a clinical level, Frost et al. (2000) compared

patients with OCD with and without hoarding and found that the former group presented

significantly higher levels of disability in working environments, family and domestic

responsibilities, social life, and leisure activities. It is still unclear, however, how social

isolation and hoarding relates to each other: either severe hoarding behavior could

discourage potential matrimonial partners or the lack of a spouse might increase the

possibility that such behavior goes on unchecked or even escalates without any consistent

opposition (Frost et al., 2004).

The SF- 36 limitation to physical health problems subscale evaluates how much the

physical health of the respondents interferes with their work or regular daily activities. In

our regression analyses, the scores on the washing subscale of the OCI–R were able to

explain 31% of the variance of this subscale. We have already discussed the possibility that

different types of compulsions (including washing) may result in physical limitations in an

independent sample (Soares, 2003). Indeed, Moritz et al. (2005) also found that washers as

categorized according to the Hamburg Obsessive– Compulsive Inventory (HOCI)

normative data, presented greater physical limitations than non- washers, It is unclear

whether the relationship between washing and physical limitations represents a mere

statistical artifact or reflects a true physical disability in a sense comparable to that

associated with many chronic medical illnesses [such as rheumatoid arthritis (Ciconelli,

1997)]. Nevertheless, it has been shown that sustained washing symptoms may lead to

physical exhaustion and to severe dermatological problems (Moritz et al., 2005). It is

noteworthy that this was the SF- 36 dimension most sensitive to treatment in Moritz et al.'s

(2005) study.

The physical functioning subscale of the SF- 36 evaluates not only the presence but

also the extension of the limitations related to functional capacity. Patients with OCD

exhibited significantly lower levels of functional capacity than age- and gender-matched

community controls. A model that included current age, the severity of comorbid

depressive symptoms, and employment status explained 53% of the variance of functional

capacity subscale of the SF- 36. These results suggest that this modality of quality of life is

more heavily influenced by certain socio-demographic features and by the presence of

comorbid depression than by any type of obsessive–compulsive symptom.

194

As expected, bodily pain scores in patients with OCD were not significantly

different from those reported by age- and gender-matched community controls. Rodriguez-

Salgado et al. (2006) described similar findings. A statistical model that included the

severity of comorbid anxiety and depression and current age explained 62% of the variance

in the SF-36 pain subscale. These findings suggest that patients with OCD and painful

complaints should be assessed for the presence of comorbid depressive or anxiety disorders

(Kroenke, 2003).

Finally, patients with OCD showed reduced vitality, general health, role-emotional

aspects, and mental health subscales scores when compared to age-and gender-matched

community controls. Indeed, depressive symptoms alone were able to explain 52% of the

variance of the vitality scale, 46% of the general health state, and 39% of the emotional

aspects of the SF-36. Additionally, depressive and anxiety symptoms together explained

67% of themental health subscale scores. Similar findingswere described by Masellis et al.

(2003),who evaluated 43 patientswith OCDwith the Illness Intrusiveness Rating Scale

(IIRS) as a measure of quality of life. In this study, the severity of depression, evaluated

bymeans of the BDI,was able to predict 54% of the variance of the scores of the IIRS,

significantly more than the severity of obsessive symptoms per se. In a study by Stengler-

Wenzke et al. (2007), depressive symptoms (as measured by the BDI) also had the

strongest negative effect on quality of life, as assessed with the WHOQOL-BREF, a self-

administered questionnaire developed by the World Health Organization. Effect sizes of

BDI scores were larger than those of the Y-BOCS subscores in all domains of the

WHOQOL-BREF, except for ‘environ mental well-being’, which includes questions

regarding physical safety and security, home environment, health and social care, among

others.

The fact that the depression and anxiety, but not hoarding symptoms, explained a

significant portion of the variance of several dimensions of the quality of life in patients

with OCD is difficult to explain. Nevertheless, we speculate that the lack of insight into the

severity of illness that characterizes individuals with hoarding symptoms (Damecour and

Charron, 1998; Storch et al., 2007) may have contributed to raise some aspects of their self-

esteem and thus different dimensions of their quality of life. On the other hand, the social

pressures experienced by the same patients with OCD and hoarding are likely to decrease

self-esteem and social functioning.

Admittedly, our study has some limitations that need to be brought to attention.

First, our sample was recruited in specialized centers and was thus unlikely to be

representative of Brazilian patients with OCD. Second, the control group was composed of

non-clinical individuals; a featuremay have led to an overestimation of their quality of life.

Third, as Stengler-Wenzke et al. (2007) have pointed out, ratings on depression scales (e.g.

BDI) and on quality of life instruments (e.g. SF-36) may be state-dependent and change

during the course of OCD. Four, in the absence of a tool specifically designed to measure

quality of life in OCD, we employed a generic instrument (the SF-36) that may not be able

to fully capture the particularities and daily difficulties of our patients. Future studies aimed

at developing a quality of life instrument to be employed in patients with OCD spectrum

disorders are badly needed. Further, while we assessed hoarding with a “sophisticated” 23-

item instrument (SI–R),we employed brief measures to assess other types of OCD

symptoms (i.e. different dimensions of the OCI–R). This may account, at least inpart, for

the different relationships observed between hoarding and non-hoarding symptoms to

quality of life identified in the current study. Five, we acknowledge that stepwise regression

195

analyses such as those we have employed have some significant limitations. Nevertheless,

given the exploratory nature of our investigation [i.e. no previous study has examined the

relationship between OCD symptom dimensions (including a hoarding measure) and

different domains of quality of life], we felt that an atheoretical approach could provide a

more unbiased basis for this preliminary exploration of this uncharted territory.

Additionally, the issue of multicollinearity is always an important limitation in research

evaluating depression and anxiety symptoms among patients with OCD. Finally, although

the number of variables included in our regression analyses could be considered somewhat

excessive, we tried to keep it to the minimum by just including items deemed essential for

our purposes. The low prevalence of comorbid conditions in our sample of patients with

OCD may be attributed to the cross-sectional nature of the study and to the fact that many

patients were undergoing psychological and/or pharmacological treatment (which included

serotonin reuptake inhibitors, benzodiazepines, and antipsychotics).

In sum, although hoarding and washing symptoms may adversely affect discrete

aspects of quality of life, our findings suggest that the severity of comorbid depression and

anxiety may be responsible for most of the deficits presented by patients with OCD.

Certainly, there is an urgent need to develop methods for social rehabilitation for patients

with OCD and hoarding symptoms. Also, the fact that limitation to physical health

problems of patients with OCD was partially explained by the severity of their washing

symptoms suggests that early treatment of these pathological behaviors may prevent the

decline of specific domains of OCD patients’ quality of life.

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199

6.8)

The Brazilian Portuguese version of the saving inventory-revised: internal consistency,

test-retest reliability, and validity.

Isabela S. Fontenelle;

a,b

Leonardo F. Fontenelle*;

a,c

Angélica M. Prazeres;

Manuela C.

Borges;

Bernard P. Rangé;

Mauro V. Mendlowicz;

Marcio Versiani

Running-Head:

Brazilian SI-R

______________________________________________________________

Anxiety and Depression Research Program, Institute of Psychiatry, Federal University of

Rio de Janeiro (IPUB/UFRJ), Rio de Janeiro, Brazil,

Postgraduate Program in Psychology, Institute of Psychology, Federal University of Rio

de Janeiro (IP/UFRJ), Rio de Janeiro, Brazil,

Department of Psychiatry and Mental Health, Institute of Community Health, Fluminense

Federal University (MSM/UFF), Niterói, Brazil,

Corresponding author:

Leonardo F. Fontenelle

Rua Visconde de Pirajá, 547, Sala 719

Ipanema, Rio de Janeiro

CEP: 22410-003

Tel and Fax: +55-21-2239-4919; E-mail: lfontenel[email protected]

200

ABSTRACT

The aim of this study is to describe the process of translation, cross-cultural adaptation, and

validation of the Brazilian version of the Saving Inventory-Revised (SI-R), an instrument

designed to measure the severity of hoarding behavior. We assessed 65 patients with

obsessive-compulsive disorder (OCD) and 70 individuals from the community (IC) with

the Structured Clinical Interview for the Diagnosis of DSM-IV (clinical sample), the SI-R,

the Obsessive-Compulsive Inventory-Revised (OCI-R), the Beck Depression Inventory,

and the Beck Anxiety Inventory. The Brazilian version of the SI-R exhibited excellent

internal consistence (Cronbach’s alpha= 0.94 in OCD and 0.84 in IC), excellent to good

test-retest reliability (r=0.94 in OCD and r=0.59 in IC) and, using the hoarding dimension

of the OCI-R as a reference point, excellent to moderate convergent validity (r=0.88 in

OCD and r=0.55 in IC). Nevertheless, the SI-R total scores correlated significantly with

comorbid anxiety (r=0.58 in OCD and r=0.42 in IC) and depressive symptoms (r=0.60).

Our findings suggest that hoarding is a construct that can be measured by the SI-R in the

Brazilian population.

Key words:

obsessive-compulsive disorder; cross-cultural; hoarding; assessment

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Introduction

Hoarding is defined as the acquisition of and failure to discard possessions of little

use or value to other people (Frost & Gross, 1993). A number of studies have indicated that

hoarding occurs across a wide spectrum of severity (Frost & Gross, 1993; Frost, Stekette, &

Williams, 2000). It has been proposed that clinically significant hoarding (1) results in

living spaces being sufficiently cluttered as to preclude normal use and activities, and (2)

creates significant distress or impairment in functioning (Frost & Hartl, 1996). Severe

hoarding behaviors may result in an inability to complete necessary household functions

(e.g., paying bills, cooking), health problems (e.g., dust allergies), conflicts with relatives,

social withdrawal, eviction, fire, and even death (Frost & Gross, 1993; Frost & Hartl, 1996;

Frost, Steketee, Youngren, & Mallya, 1999). Commonly saved items include newspapers,

magazines, old clothing, bags, books, mail, notes, and lists (Frost & Gross, 1993; Frost &

Hartl, 1996).

Samuels et al. (2006) estimated the frequency and evaluated correlates of hoarding

in 742 participants in the Hopkins Epidemiology of Personality Disorder Study. The

prevalence of hoarding in the general population was nearly 4% (5.3%, weighted) and

especially higher among older, male, and low-income individuals. Hoarding was also

associated with alcohol dependence; paranoid, schizotypal, avoidant, and obsessive-

compulsive personality disorder traits; insecurity from home break-ins and excessive early

physical discipline; and parental psychopathology.

Unfortunately, there is no community-based study of hoarding symptoms in Brazil.

Nevertheless, the lifetime prevalence rates of OCD in the Brazilian general population has

been reported to be 0.3%, in São Paulo-SP (Andrade et al., 2002), 0.7%, in Brasilia-DF

(Almeida et al., 1997), and 2.1%, in Porto Alegre-RS (Almeida et al., 1997). Since up to

202

50% of Brazilian patients with OCD may exhibit different degrees of hoarding symptoms

(Miguel et al., 2008), one can speculate that OCD-related hoarding symptoms may affect

from 0.15 to 1.05 % of the Brazilian population. As hoarding may occur in conditions other

than OCD [including obsessive compulsive personality disorder (Hummelen, Wilberg,

Pedersen & Karterud, 2008), schizophrenia (Tracy, de Leon, Qureshi, McCann, McGrory

& Josiassen, 1996) dementia (Hwang, Tsai, Yang, Liu & Lirng, 1998), anorexia nervosa

(Frankenburg, 1984), and autism (McDougle et al, 1995), among others], its real

frequency is probably much higher than the afore-mentioned figures. Clearly, there is an

urgent need to develop instruments aimed at assessing hoarding symptoms and monitoring

treatment response in Brazilian environments.

In fact, despite the growing body of evidence underlying the importance of

identifying and describing hoarding symptoms in different cultures, very few studies were

performed with the objective of developing instruments for the qualitative and quantitative

evaluation of hoarding (Frost, Steketee, & Grisham, 2004). For example, until recently,

only three self-administered instruments aimed at assessing obsessive-compulsive

symptoms included an evaluation of hoarding symptoms, i.e. the

Obsessive-Compulsive

Inventory

(OCI) (Foa, Kozak, Salkovskis, Coles, & Amir, 1998) and its compact version,

the

OCI-Revised

(OCI-R) (Foa et al, 2002), and the

Yale-Brown Obsessive-Compulsive

Scale

(Y-BOCS) Symptom Checklist (Goodman et al, 1989a; Goodman et al, 1989b). Of

note, although widely used in clinical and research settings, the Y-BOCS includes only two

yes-or-no hoarding items (Tortella-Feliu, Fullana, Caseras, Andión, Torrubia, & Mataix-

cols., 2006).

203

In 2004, Frost, Steketee, & Grisham proposed a 23-item instrument, the Saving

Inventory-Revised (SI-R), which assesses not only the three key hoarding symptoms, but

also the level of distress and the degree of dysfunction presented by individuals with

pathological hoarding. The first key symptom dimension is the excessive acquisition of

hoarding items. Accordingly, recent research has shown that the uncontrollable acquisition

of possessions (including compulsive buying and/or excessive acquirement of free items) is

an important feature of several patients with hoarding (Frost, Kim, Morris, Bloss, Murray-

Close, & Steketee, 1998). The second key symptom dimension presented by patients with

pathological hoarding is the difficulty discarding items. In general, patients with hoarding

tend to overestimate the worth of their belongings and, consequently, manifest distress

when pressured to get rid of them (Frost, Hartl, Christian, & Williams, 1995). The third key

dimension is the resulting clutter. Patients with hoarding frequently display distressed and

functional impairment due to space limitations created by the excessive number of hoarding

items, which tend to occupy otherwise free spaces that cannot be used for their original

purposes anymore (Frost & Hartl, 1996).

To the best of our knowledge, the SI-R was not translated into other languages or

populations until 2006, when Tortella-Feliu and coworkers developed a Spanish version of

the scale. Until then, the psychometric properties of the SI-R have been systematically

studied only in the US population. As can been seen in table 1, different studies and

versions of the 23-item SI-R have all shown excellent internal consistence (Coles et al.,

2003; Frost et al., 2004; Tortella-Feliu et al., 2006) with an expected improvement of test-

retest reliability in clinical populations (Frost et al., 2004). Excellent convergent validity

was demonstrated using instruments such as the Saving Cognition Inventory-Revised

(Coles et al., 2003; Frost et al., 2004) and the hoarding subscale of the Obsessive-

204

Compulsive Inventory-Revised (Tortella-Feliu et al., 2006) as reference points. Finally,

divergent validity of the SI-R has been more inconsistent, with correlations as high as 0.54

for Anxiety Sensitivity Scores (Coles et al., 2003) and as low as 0.06 for the Y-BOCS

(Frost et al., 2004).

Table 1: Summary of the psychometric features of the SI-R in other samples

Coles (2003) Tortella-Feliu (2006) Frost (2004)

Type of Sample Non-clinical Non-clinical “Clinical hoarders”

Internal consistency

R total

0.94

0.87

0.92

SI-R acquisition 0.81 0.80 0.87

SI-R clutter 0.91 0.79 0.91

R d. discarding

0.90

0.83

0.88

Test-retest reliability

SI-R total NA 0.78 0.86

SI-R acquisition NA 0.51 0.78

R clutter

0.78

0.90

SI-R d. discarding NA 0.46 0.89

Convergent validity

Reference instrument

SCI

OCI

R hoarding

SCI

SI-R total 0.62 0.48 0.73

SI-R acquisition 0.40 0.36 0.53

R clutter

0.41

0.37

0.67

SI-R d. discarding 0.63 0.41 0.72

Divergent validity

Reference instrument # 1 BDI BDI PANAS-Negative

R tota

0.42

0.38

SI-R acquisition 0.27 0.31 0.38

SI-R clutter 0.36 0.35 0.26

R d. discarding

0.34

0.21

Reference instrument # 2 ASI STAI-T YBOCS

SI-R total 0.54 0.38 0.25

SI-R acquisition 0.33 0.34 0.29

SI-R clutter 0.47 0.27 0.06

SI-R d. discarding 0.46 0.29 0.24

SI-R: Saving Inventory-Revised; SCI: Saving Cognitions Inventory; OCI-R: Obsessive-

Compulsive Inventory-Revised; BDI: Beck Depression Inventory; PANAS: Positive and Negative

Affective Scale; ASI: Anxiety Sensitivity Scale: Yale-Brown Obsessive-Compulsive Scale; STAI-

T: State and Trait Anxiety Inventory-Trait

205

In this study, our objective was to present the process of translation, cross-cultural

adaptation and validation of the SI-R to Brazilian Portuguese. Our specific research

questions were:

What is the magnitude of the difference between the total, partial, and item-by-item

SI-R scores presented by Brazilian patients with OCD and those exhibited by

Brazilian community individuals?

What is the internal consistence of the SI-R in Brazilian patients with OCD and

corresponding community individuals?

What is the test-retest reliability of the SI-R in Brazilian patients with OCD and in

corresponding community individuals?

Does the SI-R exhibit satisfactory

convergent

validity in Brazilian patients with

OCD and corresponding community individuals?

Does the SI-R exhibit satisfactory

divergent

validity in Brazilian patients with OCD

and corresponding community individuals?

Methods

Patients were consecutively selected among those under treatment in (1) the Anxiety

and Depression Research Program at the Institute of Psychiatry of the Federal University of

Rio de Janeiro (IPUB/UFRJ), (2) the Division of Applied Psychology at the Institute of

Psychology of the same university (DPA/UFRJ), and (3) the first author’s private practice.

The inclusion criteria were (1) the diagnosis of OCD, with or without psychiatric

comorbidity confirmed by means of the Structured Clinical Interview for Axis I disorders

(SCID), (2) age between 18 and 80 years, and (3) absence of any other neurological,

206

endocrinological, or systemic disorder that could interfere in our results. In the presence of

any psychiatric comorbidity, only patients who developed OCD as a primary disorder,

either in terms of chronology or of terms of severity of symptoms, were included.

The control group consisted of individuals recruited in the community by means of

local advertisements, and included members of the medical and administrative staff of the

Federal University of Rio de Janeiro. The inclusion criteria for volunteers selected to

participate in the control group were (1) age between 18 and 60 years, and (3) absence of

any other neurological, endocrinological, or systemic disorder that could interfere in our

results. Community controls were not evaluated a priori for the presence of psychiatric

disorders. With this strategy, we intended to avoid the selection of a “supernormal” sample,

which would be not representative of the general population.

Procedures

The local institutional review board approved this research protocol (SISNEP code

= CAAE - 0002.0.249.000-07). All participants signed an informed consent after a detailed

explanation of the procedures involved in the study. Patients with OCD, but not controls,

were evaluated with the Brazilian version of the SCID-IV (Del-Ben, Vilela, & Crippa,

2001). The SCID-IV is a semi structured clinical interview to be administered by the

clinicians in order to identify axis I diagnosis according to the DSM-IV criteria. Since two

different centers (IPUB/UFRJ and IP/UFRJ) were responsible for the recruitment and

administration of the SCID in the majority of cases, some questions regarding the reliability

of our methods could be raised. Nevertheless, the simultaneous psychiatric (Anxiety and

Depression Research Program) and psychological (Division of Applied Psychology)

follow-up of a significant portion of patients allowed us to discuss and reach a consensus

207

on cases presenting difficult diagnoses. Patients and controls were asked to complete

specifically designed questionnaire that covered personal information, such as age, gender,

educational level, marital and employment status, and monthly income.

Instruments

Saving Inventory – Revised (SI-R)

As reported above, the SI-R was designed to evaluate the severity of hoarding

behaviors in clinical and non-clinical populations. It is a self-administered Likert scale that

includes 23 items. The items are divided in 3 subscales: the clutter subscale, the difficulty

discarding subscale and the acquisition subscale.

Beck Depression Inventory (BDI)

The BDI is the most widely used self-rated instruments for evaluating the severity of

depressive symptoms in different populations. The BDI was chosen in order to control for

the effect of depression in our analyses. The scale has 21 items, each one consisting of four

statements describing increasing intensities of symptoms of depression. Items are rated on a

scale from 0–3, reflecting how participants have felt over the past week. Possible scores

range from 0–63, with higher scores reflect more severe depressive symptoms. The

Brazilian Portuguese version of the BDI has shown favorable psychometric properties

among the elderly, including at least satisfactory internal consistency (Cronbach’s

alpha=0.82); construct validity (r=0.65), and test-retest reliability (r=0.86) (Cunha, 2001).

Beck Anxiety Inventory (BAI)

The BAI is a self-rated instrument for evaluating the severity of anxiety in different

208

populations. The BAI was chosen in order to control for the effect of anxiety in our

analyses. The scale has 21 items describing subjective, somatic, or panic-related symptoms.

It was specifically designed to reduce the overlapping between depression and anxiety

scales by measuring anxiety symptoms shared minimally with those of depression. Items

are rated on a scale from 0–3, reflecting how participants have felt over the past week.

Possible scores range from 0–63, with higher scores reflecting more severe anxiety

symptoms. The Brazilian Portuguese version of the BAI has also shown favorable

psychometric properties among elder individuals, including at least satisfactory internal

consistency (Cronbach’s alpha=0.83), convergent validity [with the State (r=0.76)-Trait

(r=0.78) Anxiety Inventory], and test-retest reliability (r=0.99 [Cunha, 2001].

Obsessive-compulsive Inventory-Revised (OCI-R)

The OCI-R, developed by Foa et al (2002), is a revised, shorter version of the

Obsessive-Compulsive Inventory

(OCI), an instrument created by the same group of

investigators (Foa, Kozak, Salkovskis, Coles, & Amir, 1998). It is a self-administered scale

composed of 18 Likert-type items that provides a total score and 6 sub-scores. The OCI-R

was chosen because, besides hoarding, it evaluates the severity of a series of other

obsessive-compulsive symptoms, including washing, checking, ordering, rumination, and

neutralization.

The Brazilian Portuguese version of the OCI-R by Souza, Foa, Meyer, Niederauer,

Raffin, & Cordioli (2008) exhibited excellent internal consistency (0.94) and test-retest

reliability (0.98). It also displayed moderate convergent validity, using the Yale-Brown

Obsessive-Compulsive Scale as a reference point (0.47).

209

Statistical analyses

Patients with OCD (n=65) and community individuals (n=70) were included in the

analyses. The internal consistency of the SI-R was evaluated by means of the Cronbach’s

alpha. Validity and reliability measures were tested by means of Pearson’s correlation

coefficient. The test-retest reliability was studied by comparing the partial and total SI-R

scores on the baseline and after a 4 to 6 weeks interval. The convergent validity of the SI-R

and its subscales included the OCI-R hoarding item as the reference-point [an instrument

proved to be reliable in Brazil (Souza, Foa, Meyer, Niederauer, Raffin, & Cordioli, 2008)],

while the divergent validity of the SI-R and its subscales included the BDI and BAI scores

as reference-points (Cunha, 2001)]. All analyses were performed using the SPSS-10. The

statistical level of significance chosen was 5%.

RESULTS

Aspects involved in the translation of the instrument

The process of adaptation of the SI-R to Brazilian Portuguese involved the

following stages (as suggested by Reichenheim, Moraes, & Hasselmann, 2000): two

translations of the original SI-R, elaboration of the first preliminary version, back

translation of the first preliminary version, comparison with the original SI-R, and creation

of the second preliminary version, pre-test, and elaboration of the final Brazilian

Portuguese version of the SI-R.

The first stage consisted in the translation of the original instrument into Brazilian

Portuguese by two experts working independently: a notarized translator performed the first

translation (T1) and mental health professional fluent in English and with experience in the

210

evaluation and treatment of patients with OCD and pathological hoarding made the second

one (T2).

In the second stage of the process, two “new” and independent mental health

professionals compared T1 and T2, aiming to select the best literal and semantic

alternatives among those previously translated. They were told that the most simple and

familiar expressions to our patients’ milieu would be preferable. At the end of this stage,

the first preliminary version of the SI-R (T3) was created.

In the third stage of the process, another independent notarized translator translated

T3 back to English (BT3). Then, two mental health professionals compared the original SI-

R and the BT3. If any gross semantic discrepancy between these versions was found, T3

was corrected in order to correspond to the original instrument. The second preliminary

version of the SI-R was thus created (T4).

At the fourth stage, a pre-test was performed with 15 patients with OCD, so that the

comprehension of the instrument’s content could be evaluated. During this stage, following

our patients’ suggestions, only two changes were made. Firstly, some patients did not agree

that the Portuguese expression “entulho” described their possessions adequately. Some felt

that this word was closely related to rubbish, which many of them found demeaning. Thus,

“entulho” was substituted for by “acumulações” (accumulations). Secondly, the structure of

the SI-R item # 17 (originally phrased as

How often do you avoid trying to discard

possessions because it is too stressful or time consuming

?), was changed from “Com que

freqüência você evita se livrar de seus pertences porque isso é muito estressante ou

consome tempo demais?” to “Com que freqüência você deixa de jogar fora seus pertences

porque isso é muito estressante ou consome tempo demais?” The final version of the SI-R

was then created.

211

Description of the sample

At first, a total of 135 participants fulfilled our inclusion criteria: 65 patients with

OCD and 70 community individuals. The volunteers were predominantly female

individuals (n=82; 60.7 %) with a current mean age of 37.3 (±13.5) years. Sixty-nine

(51.1%) participants were single, 48 (35.6%) were married, 7 (5.2%) were divorced, 6

(4.4%) were separated and 5 (3.7%) were widowed. The volunteers had a mean of 13.2 ±

4.1 years of study and 78 (57.8%) were employed. Their average monthly income was

2.120 (± 2.172)

reais

(about 1,100 American dollars).

A comparison between the socio-demographic characteristics of our patients with

OCD and volunteers from the community is depicted on table 2. Although the mean

monthly income of patients with OCD was lower than that of community controls, this

difference did not reach statistical significance.

212

Table 2: Comparison between the socio-demographic characteristics of patients with

OCD and community controls

Socio-demographic

features

Patients with

OCD (n=65)

Community

controls (n=70)

Test results

Age (in ys) 39.3 (± 13.8) 35.5 (± 13.0) t=-1.6; df=133; p=0.1

Gender χ2=1.1; df=1; p=0.3

Female

36 (55.4%) 46 (65.7%)

Male

29 (44.6%)

24 (34.3%)

Marital status χ2=1.7; df=1; p=0.2

Married

19 (29.2%) 28 (40.0%)

Non-married

46 (70.8%) 42 (60.0%)

Education (in yr) 13.0 (±3.9) 13.4 (±4.3) t=-0.5; df=132; p=0.6

Monthly income

Personal

1.577 (±1121) 2.497 (±2.615) Z=-1.08; p=0.3

Family

2.586 (±2909) 4.257 (±4.240) Z=-1.4; p=0.1

Note=OCD: obsessive-compulsive disorder; in ys: in years

Regarding the patients with OCD, 47 (72.3%) were selected from the population

under treatment in the Anxiety and Depression Research Program from the IPUB/UFRJ, 10

(15.4%) were being treated the Division of Applied Psychology of the IP/UFRJ, and 8

(12.3%) were from the first authors’ private practice. Although it was tempting to compare

patients recruited in different centers, the low figures precluded valid analyses. In general

lines, however, they were deemed quite similar from the socio-demographic and clinical

point-of-view.

Patients with OCD reported the onset of obsessions and compulsions at

213

age14.5±10.5 and 15.9±12.7, respectively. Eleven (16.9%) patients from our OCD sample

had hoarding as their most significant obsessive-compulsive symptom. In terms of

comorbid disorders, 35.9% of the patients with OCD exhibited a current major depressive

episode; 6.3% had social phobia and 6.3% presented a dysthimic disorder. The relatively

low prevalence of comorbid conditions may be attributed to the fact that patients were

under psychological and/or pharmacological treatment. For example, 79.7% of patients

were being medicated with a serotonin reuptake inhibitor, 40% were using a

benzodiazepine, and 32.3% were being prescribed an antipsychotic. Further, 32.3% of the

patients were being treated with cognitive-behavioral therapy.

Main findings

In order to address research questions # 1, we compared the total, partial, and item-

by-item SI-R scores presented by patients with OCD to those exhibited by individuals from

the community. As seen in table 3, total and partial SI-R scores were significantly higher in

patients than controls, albeit less significantly for the acquisition subscale. Of note, none of

the acquisition items scores (i.e. 2, 9, 11, 14, 16, 18, and 21) were significantly different

between OCD patients’ and community controls (table 4).

214

Table 3: Comparison between scores different scores on the SI-R partial and total

scores between patients with OCD and community controls

OCD (SD)

CC (SD)

T value

Clutter Subscale 9.7 (10.3) 4.5 (4.2) T=3.7; df=83.2***

Difficulty Discarding Subscale

10.5 (8.3)

6.0 (4.3)

T=3.9; df=94.2***

Acquisition Subscale 8.8 (7.0) 6.6 (4.0) T=2.2; df=101.0*

Total 28.9 (22.4) 17 (10.6) T=3.8; df=89.6***

SI-R: Saving Inventory-Revised; OCD: patients with obsessive-compulsive disorder;

CC: community controls; SD: standard deviation; df: degree of freedom; *p≤0.05;

**p≤0.01; ***p≤0.001

Table 4: Comparison between scores different scores on the SI-R items between

patients with OCD and community controls

SI-R items OCD

(SD)

T value/ Z

score

1. How much of the living area in your home is cluttered with

possessions?

1.46

(1.38)

1.03

(0.98)

Z=-1.52

2. How much control do you have over your urges to acquire

possessions?

2.11

(1.35)

2.46

(1.13)

t=-1.64

3. How mu

ch of your home does clutter prevent you from using?

0.89

(1.26)

0.37

(0.68)

2.29*

4. How much control do you have over your urges to save

possessions?

2.02

(1.36)

2.34

(1.32)

t=-1.41

5. How much of you home is difficult to walk through because of

clutter?

0.65

(1.11)

(0.31)

Z=-

4.05***

6. To what extent do you have difficulty throwing things away? 1.37

(1.34)

0.89

(0.93)

Z=-1.86

7. How distressing do you find the task of throwing things away? 1.20

(1.28)

0.63

(0.92)

Z=-2.76**

8. To what extent do

you have so many things that your room(s)

are cluttered?

1.26

(1.42)

0.50

(0.74)

3.22**

9. How distressed or uncomfortable would you feel if you could not

acquire something you wanted?

1.51

(1.34)

1.09

(0.94)

Z=-1.62

10. How much does clutter in your home interfere with your social,

work, or everyday functioning?

1.03

(1.44)

0.33

(0.65)

Z=-2.86**

11. How strong is your urge to buy or acquire free things for which

you have no immediate use?

1.15

(1.31)

0.73

(0.98)

Z=-1.70

12. To what extent does clutter in your home cause you distress? 1.23

(1.39)

0.76

(1.01)

Z=-1.86

13. How strong is your urge to save something you know you may

never use?

1.38

(1.38)

0.50

(0.72)

3.88***

14. How upset or distressed do you feel about your acquiring

habits?

0.92

(1.24)

0.54

(0.77)

Z=-1.49

15. To what extent do you feel unable to control the clutter in your 1.52 0.80 Z=-2.82**

215

home? (1.43) (0.91)

16. To what extent has you saving or compulsive buying resulted

in financial difficulties for you?

0.94

(1.40)

0.64

(1.01)

Z=-0.72

17. How often do you avoid trying to discard possessions because

it is too stressful or time consuming?

1.60

(1.46)

0.96

(1.06)

Z=-2.52**

18. How often do you feel compelled to acquire something you

see?

1.40

(1.39)

1.30

(1.11)

Z=-0.17

19. How often do you decide to keep things you do not need and

have little space for?

1.31

(1.37)

0.81

(0.95)

Z=-1.86

20. How frequently does clutter in your home prevent you from

inviting people to visit?

0.75

(1.29)

0.36

(0.78)

1.67

21. How often do you actually buy (or acquire for free) things for

which you have no immediate use or need?

1.08

(1.31)

0.74

(0.81)

Z=-0.84

22. To what extent does the clutter in you home prevent you from

using parts of your home for their intended purpose?

0.97

(1.39)

0.31

(0.60)

Z=-2.70**

23. How often are you unable to discard a possession you would

like to get rid of?

1.54

(1.51)

0.67

(0.88)

Z=-

3.24***

SI-R: Saving Inventory-Revised; OCD: patients with obsessive-compulsive disorder; CC:

community controls; SD: standard deviation; *p≤0.05; **p≤0.01; ***p≤0.001

To address research questions # 2, we investigated the Brazilian SI-R Cronbach’s

in patients and community individuals. We found that, in patients with OCD, the Brazilian

version of the SI-R exhibited an alpha correlation coefficient (Cronbach’s

) of 0.94 in

terms of its total score, 0.95 on its “clutter” subscale, 0.81 on its “difficult discarding”

subscale, and 0.78 on its “acquisition” subscale. Further, in community individuals, the

Brazilian version of the SI-R exhibited an alpha correlation coefficient (Cronbach’s

) of

de 0.84 in terms of its total score, 0.78 on its clutter subscale, 0.67 on its difficult

discarding subscale, and 0.63 on its acquisition subscale.

In order to address research question # 3, we conducted a correlation analysis

between the partial and total SI-R scores on the baseline and the scores on the same

variables after a 4 to 6 weeks interval. We found that, in patients with OCD, the test retest

reliability varied from excellent, for the total SI-R scores, to good, for the acquisition scores

216

of the same scale (table 5). In community individuals, the test-retest reliability was

somewhat lower, albeit still satisfactory.

Table 5: Test-retest reliability: Pearson’s correlation between the SI-R scores obtained

in the first and second applications.

SI-R Patients with OCD Community controls

r r

Total 0.94 0.59

Clutter

0.91

0.66

Difficulty discarding 0.88 0.63

Acquisition

0.74

0.50

Note=OCD: obsessive-compulsive disorder; SI-R: Saving Inventory-Revised

To address research question # 4, we conducted a correlation analysis between the

baseline partial and total SI-R scores and the OCI-R hoarding scores. The convergent

validity of the Brazilian version of the SI-R total and partial scores was excellent among

patients with OCD (table 6) and quite reasonable in community individuals (table 7).

Nevertheless, since the total and partial SI-R subscores also correlated with other OCI-R

scores as well (more with the obsessions and less with the washing dimensions), we

performed a co-variation analyses aimed at studying the effect of the checking,

neutralizing, obsession, ordering, and washing OCI-R scores on the correlation between the

SI-R and its subscores with the hoarding item of the OCI-R found in patients with OCD.

Still, total, clutter, difficult discarding, and acquisition SI-R scores remained significantly

correlated with the OCI-R hoarding item (r= 0.86; p<0.001; r=0.82; p=<0.001; r=0.84;

p<0.001; r=0.43; p<0.001; respectively). In community individuals, the persistence of the

217

correlations with the OCI-R hoarding was not as consistent, although still significant for

most SI-R dimensions (SI-R total: r= 0.36, p=0.003; SI-R clutter: r=0.25, p=<0.04; SI-R

difficult discarding: r=0.39, p=0.001; and SI-R acquisition: r=0.22, p<0.07; respectively).

218

Table 6: Convergent validity: Pearson’s correlation between the SI-R, the OCI-R, and their subscales among patients with OCD

SI-R OCI-R

Total Clutter

Saving

Acquisition Total

Checking Hoarding Neutralization

Obsession Orderin

Washing

SI-R

Total

Clutter 0.92

Saving

0.90

0.79

Acquisition 0.77 0.56 0.55

OCI-R

Total

0.73

0.65

0.72

0.55

Checking 0.51 0.47 0.51 0.37 0.78

Hoarding 0.88 0.85 0.88 0.55 0.63 0.42

Neutralization

0.41

0.31

0.39

0.43

0.69

0.44

0.25

Obsession 0.42 0.32 0.43 0.38 0.75 0.42 0.38 0.52

Ordering 0.52 0.45 0.52 0.39 0.77 0.58 0.43 0.52 0.45

Washing 0.37 0.36 0.33 0.28 0.67 0.44 0.23 0.32 0.51 0.37

Note=SI-R: Saving Inventory-Revised; OCI-R: Obsessive-Compulsive Inventory-Revised

Table 7: Convergent validity: Pearson’s correlation between the SI-R, the OCI-R, and their subscales among community controls

219

SI-R OCI-R

Total Clutter

Saving

Acquisition Total

Checking Hoarding Neutralization

Obsession Orderin

Washing

Total

Clutter 0.84

Saving 0.85 0.57

Acquisition

0.83

0.56

0.60

OCI-R

Total 0.55 0.30 0.52 0.53

Checking

0.38

0.25

0.42

0.33

0.76

Hoarding 0.55 0.41 0.56 0.45 0.66 0.46

Neutralization

0.45 0.37 0.41 0.33 0.72 0.50 0.44

Obsession

0.40

0.24

0.28

0.54

0.62

0.23

0.40

0.37

Ordering 0.30 0.20 0.27 0.20 0.74 0.45 0.22 0.47 0.30

Washing 0.12 0.00 0.19 0.19 0.59 0.43 0.17 0.24 0.28 0.45

Note=SI

R: Saving Inventory

Revised; OCI

R: Obsessive

Compulsive Inventory

Revised

220

To assure that the correlations between the SI-R and the OCI-R were not ascribable

to comorbid anxiety and depression symptoms, we calculated the correlations between the

SI-R total and partial scores and different OCI-R scores (including hoarding subscale)

controlling for the BDI and BAI scores (tables 8 and 9). Although the magnitude of the

partial correlations was somewhat reduced in comparison with bivariate correlations, SI-R

total, clutter, difficult discarding, and acquisition remained strongly correlated to the OCI-R

hoarding scores (r= 0.84; p<0.001; r=0.78; p=<0.001; r=0.87; p<0.001; r=0.37; p=0.003;

respectively).

221

Table 8: Convergent validity: Pearson’s correlation between the SI-R, the OCI-R, and their subscales among patients with OCD,

controlling for depression and anxiety

SI-R OCI-R

Total

Clutter

Saving

Acquisition

Total

Checking

Hoarding

Neutralization

Obsession

Orderin

Washing

SI-R

Total

Clutter

0.88

Saving 0.87 0.74

Acquisition 0.67 0.34 0.39

OCI

Total 0.53 0.44 0.52 0.35

Checking 0.29 0.27 0.27 0.17 0.67

Hoarding

0.84

0.78

0.87

0.37

0.48

0.24

Neutralization

0.24 0.13 0.21 0.32 0.63 0.29 0.08

Obsession 0.19 0.08 0.23 0.20 0.68 0.24 0.20 0.41

Ordering 0.24 0.19 0.26 0.16 0.62 0.38 0.21 0.36 0.25

Washing

0.09

0.12

0.05

0.06

0.52

0.22

0.01

0.15

0.36

1.00

Note=SI-R: Saving Inventory-Revised; OCI-R: Obsessive-Compulsive Inventory-Revised

222

Table 9: Convergent validity: Pearson’s correlation between the SI-R, the OCI-R, and their subscales among community

controls, controlling for depression and anxiety

SI-R OCI-R

Total

Clutter

Saving

Acquisition

Total

Checking

Hoarding

Neutralization

Obsession

Orderin

Washing

SI-R

Total

Clut

ter

0.82

Saving 0.83 0.51

Acquisition 0.78 0.47 0.53

OCI

Total 0.44 0.27 0.44 0.41

Checking 0.29 0.17 0.35 0.22 0.71

Hoarding

0.50

0.36

0.51

0.36

0.60

0.39

Neutralization

0.44 0.39 0.38 0.28 0.64 0.41 0.36

Obsession 0.28 0.12 0.17 0.46 0.58 0.14 0.35 0.32

Ordering 0.16 0.08 0.14 0.14 0.66 0.34 0.07 0.32 0.19

Washing

0.01

0.07

0.11

0.08

0.55

0.38

0.08

0.16

0.22

0.39

Note=SI-R: Saving Inventory-Revised; OCI-R: Obsessive-Compulsive Inventory-Revised

223

In order to address research question number 5, we conducted a correlation analysis

between the baseline partial and total SI-R scores and the BDI and BAI scores. Moderate

correlations were found between the total and partial scores of the SI-R and the BDI and

BAI scores, suggesting an overlapping of hoarding, depression, and anxiety, most

noticeable in the treatment-seeking OCD sample (table 10).

Table 10: Divergent validity: Pearson’s correlation between the SI-R, the BDI, and the

BAI in different samples

SI-R Patients with OCD (n=65) Community controls (n=70)

BDI BAI BDI BAI

r r r R

Total 0.60 0.58 0.32 0.42

Clutter

0.58

0.54

0.21

0.28

Difficulty discarding 0.51 0.52 0.28 0.31

Acquisition 0.48 0.45 0.34 0.48

Note=SI-R: Saving Inventory-Revised; BDI: Beck Depression Inventory; BAI: Beck

Anxiety Inventory.

224

Discussion

We investigated the psychometric properties of the Brazilian Portuguese version of

the SI-R in two samples: Brazilian patients with OCD and individuals from the community.

In general, our findings are similar to those described in previous studies. As expected, the

internal consistent of the Brazilian version of the SI-R was excellent among patients with

OCD (0.94), similarly to that found in the clinical sample described in Frost and

coworkers’ study (2004). Although the internal consistence was good in the community

sample (0.84), it was somewhat inferior to that observed in our treatment seeking

individuals with OCD, a finding that was also reported in Spanish university students by

Tortella-Feliu, Fullana, Caseras, Andión, Torrubia, & Mataix-Cols (2006).

In patients with OCD, the test retest reliability varied from excellent, for the total

SI-R scores, to good, for the acquisition scores of the same scale. In community

individuals, the test-retest reliability was somewhat lower, albeit still satisfactory. Likewise,

in patients with OCD, the correlations observed between the SI-R subscales and the OCI-

R´s hoarding were, in general, excellent (although somewhat inferior for the acquisition

subscale). The correlations between the SI-R and its subscales and the checking,

neutralizing, obsessing, ordering, and washing items of the OCI-R, were quite inferior to

that reported for SI-R and its subscales and OCI-R´s hoarding. In community individuals,

the same correlations were only reasonable, a finding in accordance with those described in

a non-clinical sample by Tortella-Feliu and coworkers (2006).

Indeed, the distinctive psychometric features of the SI-R in different samples may

reflect restriction of range in the community sample and/or the salience of hoarding

symptoms in patients with OCD. Clearly, patients with OCD and pathological hoarding

225

may identify their abnormal behaviors more readily and reproduce them in a more

consistent way.

As seen in table 3, total and partial SI-R scores were significantly higher in patients

than controls, albeit less significantly for the acquisition subscale. Indeed, none of the

acquisition items scores were significantly different between OCD patients’ and to

community controls. These findings may be interpreted in at least two ways.

First, they may reflect the fact that OCD is a heterogeneous disorder, and hoarding

is just one of its putative subtypes. The inclusion of a significant number of patients with

OCD without hoarding as their main significant symptom may have lessened the

differences in terms of acquisition behaviors between patients and controls. Second, while

saving (and clutter) may be particularly associated with OCD (as reported by Mueller et al.,

2007), the prevalence of excessive acquisition behaviors among patients with OCD may not

be that different from the one exhibited by individuals from the community. In fact, it is

possible that hoarding is a heterogeneous condition itself, resulting either from compulsive

saving in OCD and impulsive acquisition in other conditions, such as compulsive shopping

or kleptomania (Maier, 2004).

The divergent validity was evaluated by means of bivariate correlations between the

SI-R and its subscales and the severity of symptoms of depression and anxiety, as measures

by the BDI and the BAI, respectively. Although correlations indicate rather clearly that the

SI-R scores were much more highly related to scores indicating hoarding behavior (i.e.

OCI-R hoarding) than to those indicating anxiety and depression (tables 8 and 9),

we still

found that the correlations between hoarding, depression, and anxiety were quite

significant, sometimes even greater than those between hoarding and other OCD

symptoms, especially in patients with OCD (table 10). These findings, in accordance with

226

those reported by Coles, Frost, Heimberg, & Steketee (2003) and Tortella-Feliu, Fullana,

Caseras, Andión, Torrubia, & Mataix-Cols (2006), may have different meanings.

Firstly, these correlations may point toward a lack of divergent validity of the SI-R,

i.e. the scale would be unable to disentangle depression and anxiety from hoarding.

Secondly, these correlations may indicate that anxiety and depression symptoms are, in

fact, a fundamental part of hoarding. Finally, the fact that the bivariate correlations between

the SI-R, the BDI, and the BAI corresponded or were even greater than that reported

between the SI-R and other dimensions of the OCI-R (such as checking, neutralization,

obsession, ordering, and washing) suggests that hoarding is more related to depressive and

anxiety symptoms than to other obsessive-compulsive symptoms. Indeed, these findings

strengthen and expand the previous report by Wu and Watson (2005), who found, in mixed

psychiatric and non-clinical samples, that (1) classic OCD symptoms of checking, rituals,

and contamination correlated consistently strongly with one another, (2) hoarding

correlated only moderately with these OCD symptoms, and (3) hoarding correlated with

depression more than one could expect.

Since pathological hoarding has been associated with particular socio-demographic,

clinical and neurobiological features, some investigators have suggested that hoarding may

deserve a separate designation as an autonomous obsessive-compulsive spectrum disorder

in the DSM-V (Saxena, 2007; Hollander, Kim & Zohar, 2007), along with body

dysmorphic disorder and trichotillomania, for example (Hollander, Kim & Zohar, 2007).

For example, Wu and Watson (2005) argued that hoarding currently is not—and never has

been—a formal diagnostic criterion of OCD and is not even discussed within DSM as an

example of OCD. As such, they suggest that researchers might consider carefully their

decisions to (a) use hoarding as a specific marker of OCD, (b) lump hoarding with classic

227

OCD symptoms to create total scores, or (c) view hoarding as a ‘‘subscale’’ within OCD

measures.

Our paper has some significant limitations. For example, the small number of

research subjects enrolled in our study precluded us from performing reliable factor

analysis of the Brazilian SI-R items. As a rule of thumb, factorial analyses studies require a

significant number of participants, i.e. 5 to 20 individuals per item of the evaluated

instrument. Since the SI-R has 23 items, 115 (5X23) to 460 (20X23) participants would be

needed to conduct these analyses. Despite including a total of 135 individuals, our sample

was composed of 65 patients with OCD and 70 community individuals. As seen above, the

Brazilian version of the SI-R behaves differentially when employed in clinical and non-

clinical populations and it is unclear how such mixed sample would affect the properties of

the SI-R. Finally, while our findings can be generalized to an OCD population and to

community individuals, they do not necessarily reflect the properties of SI-R in Brazilian

hoarders who do not have OCD. Future studies, enrolling a greater number of patients and

controls, and including individuals with primary hoarding symptoms, are needed in order to

elucidate the psychometric properties of the Brazilian version of the SI-R.

In sum, the Brazilian version of the SI-R exhibited excellent internal consistent and

convergent validity, specially among patients with OCD, and revealed inconsistent results

regarding its divergent validity, a finding that may challenge the current nosological status

of pathological hoarding as a mere symptom of OCD.

228

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