Introdução: O transtorno obsessivo-compulsivo (TOC) é uma doença de etiologia complexa, podendo ser influenciada por inúmeros fatores genéticos e ambientais. A falta de homogeneidade na descrição do transtorno dificulta a pesquisa de fatores etiológicos. Um dos subgrupos de TOC com características mais homogêneas é o TOC de início precoce. O objetivo principal deste estudo é investigar o efeito da idade de início dos diversos sintomas nas características clínicas dos transtornos psiquiátricos do Eixo I na trajetória evolutiva de pacientes com TOC. Metodologia: 1001 pacientes com TOC de acordo com os critérios do DSM-IV foram avaliados de forma direta com os instrumentos: Escala Dimensional para Avaliação de Presença e Gravidade de Sintomas Obsessivo-Compulsivos (DY-BOCS), Escala Yale-Brown de Sintomas Obsessivo-Compulsivos (Y-BOCS), Entrevista Clínica Estruturada para o DSM-IV - Transtornos do Eixo I (SCID-I/P), Inventários de Ansiedade e de Depressão de Beck, Questionário de História Natural do TOC e Escala de Crenças de Brown. Para comparação das variáveis categoriais foram realizados os testes qui-quadrado e para variáveis numéricas testes não paramétricos de Kruskal-Wallis e testes paramétricos tipo ANOVA. Foram considerados para todos os testes nível de significância de 5%. O estudo das idades de início das comorbidades foi realizado utilizando a abordagem bayesiana. Resultados: Pacientes com início precoce tiveram maior frequência de Ansiedade de Separação (p<0,001); Transtorno de Déficit de Atenção e Hiperatividade (p=0,031); Tiques (p=0,009); Espectro Obsessivo-Compulsivo (OC) (p<0,001); Transtornos do Impulso (p=0,005); e do Humor (p=0,020). Além disso, tiveram maior gravidade em todas as medidas de escore nas escalas Y-BOCS (p<0,001) e DY-BOCS (p<0,001), curso com piora progressiva do TOC (p<0,001) e maior frequência de história familiar de TOC (p<0,001) e transtornos de Tiques (p=0,013). Pacientes com TOC que apresentaram ansiedade de separação como primeiro diagnóstico tiveram uma tendência a apresentar maior frequência de: Transtornos Ansiosos (p=0,058), Somatoformes (p=0,056), TEPT (p=0,004), maior gravidade na dimensão Sexual/Religioso (p=0,053) e escores mais elevados nas escalas Beck depressão (p=0,005) e Beck ansiedade (p<0,001). Pacientes com TOC que apresentaram TDAH como primeiro diagnóstico tiveram maior frequência de Abuso de Substância (p<0,001) e apresentaram um curso com piora mais progressiva do TOC comparados com os outros grupos (p=0,033). Pacientes com TOC que apresentaram transtornos de tiques como primeiro diagnóstico tiveram maior frequência de Transtornos do Espectro OC (p=0,034). Conclusão: O TOC é um transtorno heterogêneo que pode compreender diversos subtipos de acordo com a abordagem escolhida / Introduction: Obsessive-Compulsive Disorder (OCD) has a complex etiology, and can be influenced by several genetic and environmental factors. The lack of homogeneity in the description of the disorders complicates the search for etiological factors. The main goal of this study is to verify the effect of age at onset of several symptoms in the clinical characteristics of Axis I psychiatric disorders in the trajectory of OCD patients. Methodology: 1,001 consecutive OCD patients were evaluated at a single time point. Standardized instruments were used: Structured Clinical Interview for Diagnosis of Axis I, according to DSM-IV and for impulse-control disorders; Yale-Brown Obsessive-Compulsive Scale, Dimensional Yale-Brown Obsessive-Compulsive Scale, Beck Depression and Anxiety Inventories and Brown Beliefs assessment Scale; and the Natural History Questionnaire. Chi-square test was used for categorical variables, and Kruskal-Wallis and ANOVA tests were used for continuous variables. For all the tests the significant level was considered p <.05. To analyze the distribution of comorbidities according to age at onset a Bayesian approach was used. Results: Patients with early age at onset had higher frequency of separation anxiety disorder (p<0.001), attention deficit hyperactivity disorder (ADHD) (p=0.031); tic disorders (p<0.009); obsessive-compulsive spectrum disorders (p<0.001); impulse-control disorders (p=0.005) and mood disorders (p=0.020). Besides, they presented higher severity of all measures of Y-BOCS score (p<0.001) and DY-BOCS score (p<0.001), OCD course with progressive worsening (p<0.001) and higher frequency of family history of OCD (p<0.001) and tic disorders (p=0.013). OCD patients who presented separation anxiety disorder as the first manifested diagnosis had higher frequencies of: anxiety disorders (p=0.058), somatoform disorders (p=0.056), post-traumatic stress disorder (p=0.004), higher frequency of Sexual/Religious dimension (p=0.053) and higher scores on Beck depression (p=0.005) and Beck anxiety (p<0.001). OCD patients who presented ADHD as first manifested diagnosis presented higher frequency of substance abuse (p<0.001) and presented more OCD course with progressive worsening (p=0.033). OCD patients who presented tic disorder as first manifested diagnosis presented higher frequency of OC spectrum disorders (p=0.034). Conclusion: We can conclude that OCD is a heterogeneous disorder and may include several subtypes according to the chosen approach

INTRODUÇÃO: O caráter familial do transtorno obsessivo-compulsivo (TOC) já é bem estabelecido. O gene da catecol O-metiltransferase (COMT) vem sendo objeto de estudo na genética de transtornos mentais, como o TOC. No caso deste transtorno, os resultados de estudos de associação com o gene da COMT são, em sua maioria, contraditórios. Meta-análises prévias, todas elas conduzidas com limitações metodológicas, encontraram achados também divergentes. Nesta tese, foram realizadas: uma revisão sistemática da literatura sobre estudos de associação baseados em famílias envolvendo o polimorfismo Val158Met do gene da COMT e o TOC e duas meta-análises, uma convencional e outra bayesiana, a fim de sintetizar os achados sobre este tema. MÉTODOS: Este trabalho seguiu o protocolo para revisão sistemática e meta-análise da Rede de Epidemiologia Genética Humana (HuGE). A busca por estudos de associação baseados em famílias foi feita em cinco bases de dados eletrônicas, assim como foram pesquisados estudos não publicados, dentre os quais um estudo ainda inédito, liderado pela autora desta tese. A meta-análise convencional foi calculada com o auxílio do programa STATA V. 11 e a bayesiana a partir da média das verossimilhanças. Foram investigados os viéses de publicação, heterogeneidade, além de análise de sensibilidade e metarregressão. RESULTADOS: O estudo original, que contou com 83 trios, conduzido pela autora desta tese, não encontrou associação entre COMT e TOC. Este estudo, em conjunto com mais oito estudos (seis estudos publicados e dois não publicados), foram incluídos na meta-análise. As meta-análises com método convencional e bayesiano não encontraram associação entre o polimorfismo Val158Met do COMT e o TOC na amostra total, nem nas amostras separadas por gênero. CONCLUSÕES: Contrariando meta-análises prévias, os achados deste estudo não demonstraram associação entre COMT e TOC. No entanto, a participação do gene da COMT em subgrupos específicos do TOC e em seus endofenótipos de risco ainda merece ser investigada / BACKGROUND: Obsessive-compulsive disorder (OCD) has long been considered a familial disorder. The catechol-O-methyltransferase gene has been studied in several mental disorders, including OCD. Particularly in this disorder, the findings of an association between COMT and OCD are inconclusive. Previous meta-analyses, which were conducted with several methodological limitations, found conflicting results. This work comprises: a systematic literature review regarding family-based association studies involving the COMT Val158Met polymorphism and OCD, and two metaanalyses, a conventional and a Bayesian meta-analysis, to summarize the findings on this subject. METHODS: This study was performed according to the Human Genome Epidemiology network (HuGE) guidelines for systematic review and meta-analysis. The search for family-based association studies were conducted in five electronic databases and in sources from unpublished studies. An original unpublished study, led by the author of this thesis, was included in the meta-analysis. The conventional meta-analysis was calculated with the STATA V.11 software and the Bayesian meta-analysis through the likelihood mean. Publication bias and heterogeneity were investigated. Sensitivity analysis and meta-regression were also performed. RESULTS: The original study with 83 OCD trios, conducted by the author of this thesis, found no association between COMT and OCD. This study, together with eight other studies (six studies being published and two unpublished), were included in the meta-analysis. Meta-analyses with the conventional and Bayesian method found no association between the COMT Val158Met polymorphism and OCD in the total, female-only or male-only samples. CONCLUSIONS: Different from previous meta-analyses, this study does not support the association between COMT and OCD. However, the involvement of the COMT gene in specific subgroups of OCD or endophenotypes associated with a risk for OCD should be further investigated

O transtorno obsessivo-compulsivo (TOC) é um transtorno de ansiedade caracterizado pela presença de obsessões e/ou compulsões, que interferem no funcionamento cotidiano do indivíduo. Obsessões são pensamentos, imagens, idéias ou impulsos intrusivos, repetitivos, que costumam gerar desconforto. Compulsões são comportamentos repetitivos, realizados em geral em resposta às obsessões, com a função de aliviar o sofrimento causado pelas mesmas. O TOC apresenta alta taxa de comorbidades psiquiátricas, como depressão, transtornos de tiques, e outros transtornos de ansiedade, e existem evidências de que quanto maior o número de comorbidades psiquiátricas, pior é a resposta ao tratamento do TOC. Entretanto, pouco se sabe sobre a repercussão do tratamento do TOC nos demais transtornos psiquiátricos que, com certa freqüência, o acompanham. O objetivo deste estudo foi investigar o impacto dos tratamentos convencionais do TOC sobre as comorbidades psiquiátricas detectadas na entrevista diagnóstica realizada no pré-tratamento. Foram avaliados os pacientes com diagnóstico principal de TOC, admitidos nos projetos de tratamento do Programa Transtornos do Espectro Obsessivo-Compulsivo (PROTOC) do IPq-HC-FMUSP, entre Julho de 2007 e Dezembro de 2009. Os participantes foram avaliados após 3 e 12 meses de tratamento, quanto à resposta ao tratamento do TOC e quanto à melhora dos demais transtornos psiquiátricos comórbidos. Os dados obtidos foram analisados de forma a se verificar possíveis relações entre a resposta ao tratamento do TOC e a evolução das comorbidades no curto e médio prazos. Os resultados mais robustos mostraram associação entre a resposta ao tratamento do TOC e a resposta positiva dos transtornos depressivos e ansiosos, e também dos transtornos de tiques. Interessante notar que para esta amostra, ter comorbidades psiquiátricas não se associou, estatisticamente, a uma pior resposta ao tratamento. Estudos futuros poderiam se prolongar neste tema, e estudar amostras com de maior número e distribuições mais igualitárias entre os tipos de tratamento do TOC (medicação e terapia) e entre os grupos de transtornos psiquiátricos adicionais. / Obsessive-compulsive disorder (OCD) is an anxiety disorder characterized by the presence of obsessions and/or compulsions that cause great impairment in the daily life of patients. Obsessions are thoughts, images, ideas or impulses that are persistent and experienced as intrusive, repetitive and cause anxiety or distress. Compulsions are repetitive behaviors or mental acts executed, in general, in response to obsessions and are intended to prevent or reduce the distress caused by them. OCD is also a chronic disorder that present high rates of psychiatric comorbidities such as depression, tic disorders and other anxiety disorders, and there is some evidence that the higher the number of psychiatric comorbidities, the worse the OCD treatment response. However, little is known about the impact of OCD treatment on the outcome of the psychiatric comorbidities usually present in OCD patients. The aim of this study was to investigate the impact of exclusive, conventional treatments for OCD on the outcome of additional psychiatric disorders of OCD patients detected at baseline. Patients with primary OCD admitted to the treatment protocols of the Obsessive-Compulsive Spectrum Disorders Program (PROTOC - IPq-HC-FMUSP), between July 2007 and December 2009, were evaluated at pre-treatment and after 3 and 12 months, with regard to OCD treatment response and psychiatric comorbidities status. The data were analyzed to verify possible associations between OCD treatment response and the outcome of psychiatric comorbidities. Results showed a significant association between OCD treatment response and improvement of major depression, dysthimia, other anxiety and tic disorders. Further research focusing on the possible mechanisms by which OCD treatment could lead to improvement of these specific disorders is warranted.

Background: Functional imaging studies have examined the neural circuitry of subjects with obsessive compulsive disorder (OCD), and the changes associated with oral treatment. However, the effect of intravenous (IV) serotonin reuptake inhibitors (SRIs) on neuronal activation has not been investigated in OCD subjects, even though IV SRIs have been shown to be more effective than oral pharmacotherapy. Methods: Six OCD and 6 control subjects underwent functional magnetic resonance imaging while receiving infusions of citalopram and placebo, in a randomized, crossover design. Results: Compared to controls, OCD subjects exhibited hyperactivation of the orbitofrontal cortex and anterior cingulate cortex while looking at symptom provoking pictures at baseline. However, after the citalopram infusion, patients displayed attenuations of these regions, which correlated with reductions in subjective anxiety ratings. Conclusion: The effects observed after the IV citalopram infusion are similar to modulations observed after prolonged oral pharmacotherapy trials, illustrating the benefits of IV SRIs.

Background: Functional imaging studies have examined the neural circuitry of subjects with obsessive compulsive disorder (OCD), and the changes associated with oral treatment. However, the effect of intravenous (IV) serotonin reuptake inhibitors (SRIs) on neuronal activation has not been investigated in OCD subjects, even though IV SRIs have been shown to be more effective than oral pharmacotherapy. Methods: Six OCD and 6 control subjects underwent functional magnetic resonance imaging while receiving infusions of citalopram and placebo, in a randomized, crossover design. Results: Compared to controls, OCD subjects exhibited hyperactivation of the orbitofrontal cortex and anterior cingulate cortex while looking at symptom provoking pictures at baseline. However, after the citalopram infusion, patients displayed attenuations of these regions, which correlated with reductions in subjective anxiety ratings. Conclusion: The effects observed after the IV citalopram infusion are similar to modulations observed after prolonged oral pharmacotherapy trials, illustrating the benefits of IV SRIs.

The main objective of this study was to examine the vulnerability factors of Obsessive Compulsive Symptomatology (OCS) in a non-clinical sample. On the basis of Salkovskis&rsquo / cognitive model of OCD, the present study aimed to investigate the role of perceived parental rearing behaviors, responsibility attitudes, and life events in predicting OCS. Furthermore, the mediator role of responsibility attitudes in the relationship between perceived parental rearing behaviors and OCS was examined. Finally, the specificity of these variables to OCS was evaluated by examining the relationship of the same variables to depression and trait anxiety. Analysis of covariance results showed that subjects with higher OCS scores perceived their mothers&rsquo / and fathers&rsquo / rearing behaviors as more overprotective than the subjects with lower OCS scores. The results of the regression analysis showed that perceived mother overprotection, responsibility attitudes and life events significantly predicted OCS. Furthermore, responsibility attitudes mediated the relationship between perceived mother overprotection and OCS. The predictive role of perceived mother overprotection was found to be OCS specific. On the other hand, for depression, perceived mother rejection and father emotional warmth, and for trait anxiety, perceived mother emotional warmth had significant predictive effects. While responsibility attitudes were found to be a common predictor for OCS and trait anxiety, its mediator role was OCS specific. OCS, depression and trait anxiety were all significantly predicted by life events. The results of the study were discussed within the relevant literature, and limitations of the study, suggestions for future studies, and clinical implications of the findings were presented.

The main aim of the present study was to better understand the influence of nationality/religious affiliation and degree of religious devoutness on OCD symptoms, more specifically scrupulosity symptoms and beliefs by comparing the Turkish Muslim students with the Canadian Christians who show different degrees of religiosity. To clarify the effect of religiosity on OCD symptomatology, Bible school and Divinity school students were included in the present study as an extreme religious group. Furthermore, the present study was aimed to examine the cross-cultural differences in the prevalence, content, appraisal and control of intrusions, using a structured interview methodology. Religiosity, guilt and scrupulosity scales and interview schedule were adapted into Turkish. The analyses revealed that the psychometric properties of the adapted measurements were satisfactory. Then, the effect of religiosity and religious affiliation on the experience of OCD symptoms, scrupulosity, and OCD relevant beliefs were examined via univariate and multivariate analyses. Results revealed that the effect of religiosity and nationality were significant for general distress. Results also revealed that regardless of nationality, high religious individuals reported higher degree of OCD and scrupulosity symptoms, and dysfunctional obsessive beliefs than low religious ones. The effect of religiosity on OCD and scrupulosity symptoms differed by religious affiliation. High religious Muslim students reported higher degree of compulsions, and fear of God symptoms than high religious Christians. Furthermore, religiosity and nationality affected obsessive beliefs differently. Turkish students reported higher level of perfectionism and intolerance for uncertainty in comparison with Canadian students. These results were supported by subsequent regression analyses. Furthermore, interview data showed that except for the frequency of the intrusions, the content of the intrusions was almost universal, and frequency and distress as a response to intrusions is very low in the normal population. Nationality and degree of religiosity revealed some minor differences in primary and secondary appraisals, and control strategies. These factors were specifically significant for religious and sexual intrusions. Results suggested that the religious affiliation and degree of religiosity may provide content for intrusions, rather being a causal factor. Keywords: Intrusive thoughts, Obsessive-Compulsive Symptoms, Faulty belief domains and appraisal, Religiosity and Religious Affiliation

Arguments have been made for dimensional models over categorical for the classification of personality disorder, and for the five-factor model (FFM) in particular. A criticism of the FFM of personality disorder is the absence of measures designed to assess pathological personality. Several measures have been developed based on the FFM to assess the maladaptive personality traits included within existing personality disorders. One such example is the Five-Factor Obsessive-Compulsive Inventory (FFOCI). The current study applied item response theory analyses (IRT) to test whether scales of the FFOCI are extreme variants of respective FFM facet scales. It was predicted that both the height and slope of the item-response curves would differ for the conscientiousness-based scales, due to the bias towards assessing high conscientiousness as adaptive in general personality inventories (such as Goldberg’s International Personality Item Pool; IPIP). Alternatively, the remaining FFOCI scales and their IPIP counterparts were predicted to demonstrate no significant differences in IRCs across theta. Nine hundred and seventy-two adults each completed the FFOCI and the IPIP, including 377 undergraduate students and 595 participants recruited online. A portion of the results supported the hypotheses, with select exceptions. Fastidiousness and Workaholism demonstrated the expected trends, with the FFOCI providing higher levels of fidelity at the higher end of theta, and the IPIP demonstrating superior coverage at the lower end of theta. Other conscientiousness scales failed to demonstrate the expected differences at a statistically significant level. In this context, the suitability of IRT in the analysis of rationally-derived, polytomous scales is explored.

This study investigated the effects of responsibility attitudes, locus of control and their interactions on general obsessive-compulsive (OC) symptomatology and dimensions of OC symptoms. Research subjects consisted of 385 senior high school students from Fatih Sultan Mehmet High School in Ankara. The students were given the Turkish version of Responsibility Attitudes Scale (RAS), the Maudsley Obsessive-Compulsive Inventory (MOCI), the Locus of Control Scale (LCS), the Beck Depression Inventory (BDI), and the Trait- State Anxiety Inventory-Trait Anxiety Form (TAI). The factor analysis of MOCI revealed three-factor solution. The factors were labeled as rumination, cleanliness/meticulousness, and checking. In order to examine possible gender differences, separate analyses of variance were conducted for the variables of general obsessive-compulsive symptomatology, and symptom subtypes. Results indicated that cleaning was the most common symptom subtype, followed by rumination and checking symptoms among Turkish high school students. Related to the gender differences, females reported more OC symptoms than males. Furthermore, females received significantly higher scores for cleaning subscale than male. Hierarchical regression analyses were performed to examine the relationships between responsibility attitudes, locus of control and their interactions on general OC symptomatology and its symptom subtypes in high school student sample. It was found that there was a significantly positive relationship between responsibility attitudes and general OC symptomatology. However, locus of control was not a significant predictor of general OC symptomatology. Furthermore, results revealed that there was a significant interaction effect of responsibility attitudes with locus of control on OC symptomatology. That is, an inflated sense of responsibility and the presence of external locus of control produced the highest OC symptoms. However, when the level of responsibility attitudes was low, externality or internality did not influence the levels of OC symptom. Related to dimensions of OC symptoms, responsibility was a weak predictor of rumination symptoms, and moderate predictor of cleanliness and checking symptoms. It was almost equally relevant for cleaning and checking symptoms. Locus of control and its interaction with responsibility attitudes only significantly predicted rumination symptoms. These results suggested that if the individual shows an overt behavior to prevent the external danger, locus of control does not play a significant role in OCD. The findings of the present study were discussed with current literature.

Thesis (M.S.)--Mississippi State University. Department of Psychology. / Title from title screen. Includes bibliographical references.