Objetivos. Esta tese vai ao encontro da proposta da psiquiatria do desenvolvimento, investigando sintomas clínicos, fatores de risco e potenciais endofenótipos que possam colaborar com diagnósticos precoces e o desenvolvimento de estratégias de prevenção. Métodos. O primeiro estudo relata a investigação e caracterização de uma amostra de crianças e adolescentes em risco para o desenvolvimento do transtorno obsessivocompulsivo (TOC). Para este propósito, 66 crianças e adolescentes com um familiar de primeiro grau com diagnóstico de TOC tiveram seus dados analisados de acordo com a presença ou ausência de sintomas obsessivocompulsivos. O segundo estudo consistiu no desenvolvimento e testagem de um paradigma dot probe de viés atencional relacionado a sintomas do TOC e na sua investigação enquanto possível endofenótipo do transtorno. Para tanto, três grupos de crianças foram selecionados: crianças com diagnóstico de TOC, em alto risco para o desenvolvimento de TOC (com presença de sintomas obsessivo-compulsivos e história familiar de primeiro grau de TOC) e crianças controle. O paradigma incluiu pares de estímulos aversivos (ativos) e neutros das dimensões de sintomas de contaminação/limpeza e simetria apresentados em 500 ms e 1250 ms. Resultados. O primeiro estudo obteve três resultados importantes. Primeiro, a amostra de crianças com familiar de primeiro grau com TOC apresentou elevada prevalência de sintomas obsessivo-compulsivos, confirmando a familiadade do transtorno. Segundo, crianças com e sem sintomas obsessivo-compulsivos apresentam prevalências diferentes de comportamento coercivo relacionados ou não aos sintomas obsessivo-compulsivos. Terceiro, familiares de crianças com sintomas obsessivo-compulsivos apresentaram mais frequentemente a dimensão de sintomas de contaminação/limpeza do que familiares de primeiro grau de crianças sem sintomas obsessivo-compulsivo. O segundo estudo teve como principais resultados: 1) crianças com TOC apresentam índices mais altos de desconforto pelos estímulos ativos comparados aos dos outros dois grupos de crianças, indicando que o paradigma é eficiente na sua avaliação; 2) a avaliação dos estímulos ativos da dimensão de contaminação/limpeza está associada à presença de seus respectivos sintomas no sujeito; 3) o grupo de crianças com TOC apresentou viés atencional na direção do estímulo aversivo em todas as quatro condições do paradigma (contaminação/limpeza e simetria com 500ms e 1250ms); 4) crianças com TOC apresentaram viés atencional maior do que crianças em risco para o desenvolvimento de TOC e controles sucessivamente, sempre na direção do estímulo aversivo exceto, no paradigma de simetria de 500ms; 5) O viés atencional na direção do estímulo ativo de contaminação no paradigma de 1250ms está associado à presença da dimensão de sintomas de contaminação. Conclusões. Os achados aqui descritos reforçam a familialidade do TOC, contribuem com achados de características associadas ao transtorno na infância e adolescência, reforçam a presença de um marcador de risco importante para o desenvolvimento de estratégias de detecção e prevenção precoces. Os resultados encontrados têm importantes implicações para a melhora do conhecimento de fatores de risco para o desenvolvimento do TOC e características associadas, que devem ser considerados em contextos clínicos e de pesquisa / Objective. This thesis goes in line with the concept of developmental psychiatry investigating clinical symptoms and risk factors that can further provide earlier diagnoses and preventive interventions. Methods. The first study reports the investigation and characterization of a sample of children and adolescents at risk for the development of obsessive compulsive disorder (OCD). For this purpose, 66 children and siblings with a first degree relative diagnosed with OCD had their clinical data analyzed according to the presence of obsessive compulsive symptoms. The second study consisted on the development and testing of an attentional bias dot probe paradigm with OCD relevant content to evaluate pediatric patients with OCD and further investigate it as a possible phenotype of OCD. For this purpose three groups of children were selected: 1) children with OCD; 2) children at risk for OCD (presenting obsessive compulsive symptoms and with a first degree relative diagnosed with OCD); 3) control group (children with none of the Axis I Psychiatric diagnoses). The paradigm included pairs of aversive (active) and neutral stimulus of contamination/cleaning and symmetry symptom dimensions and had two different time presentations of the stimulus, 500 and 1250 milliseconds. Results. The first study had with tree main findings. First, our sample of children with a first degree affected with OCD had a very high prevalence of obsessive-compulsive symptoms, confirming the familiality of the disorder. Second, children with and without obsessive-compulsive symptoms presented different rates of coercive behaviours, that can be related or not to obsessive-compulsive symptoms. Third, first degree relatives of children who had obsessive compulsive symptoms had significantly more contamination/cleaning dimension of obsessive compulsive symptoms than relatives of children without obsessive compulsive symptoms. The second study had the following main findings: 1) children with OCD had higher rates of discomfort caused by active stimulus than the other two groups of children, indicating that the paradigm is efficient for its purpose; 2) the evaluation of active stimulus of the contamination/cleaning dimension is associated to the presence of its respective symptoms; 3) the group of children with OCD had attentional bias towards the active stimulus in all four conditions of the paradigm (cleaning/contamination and symmetry in 500ms and 1250ms); 4) children with OCD had higher attention bias than children at risk and controls always towards the active stimulus with the exception of the 500 ms symmetry paradigm; 5) the attentional bias towards the active stimulus in the 1250 ms contamination paradigm is associated to the presence of symptoms of the contaminations dimension. Conclusions. The results reinforce the familiality of OCD, contributing with findings of associated characteristics to the disorder in childhood and adolescence and reinforcing the presence of an important risk marker for the development of strategies of early detection and prevention. The results have important implications to the improvement of the knowledge of OCD and associated characteristics, which should be considered in clinical and research contexts

A Compra Compulsiva (CC) está atualmente classificada como um transtorno do controle dos impulsos não classificados em outro local (TCI). A prevalência das CC é estimada em cerca de 5% da população geral e é identificada com maior frequência no gênero feminino. O comportamento repetitivo e crônico do comportamento de gastar descontroladamente gera consequênias negativas ao indivíduo, além dos elevados índices de comorbidades com transtorno de humos, ansiedade e outros TCIs, o que contribui para manter a divergência existente sobre a classificação da CC. Tem sido proposto que CC deve ser classificada como um TCI, ou como uma sub-síndrome do transtorno afetivo bipolar (TAB), ou ainda como uma variante do transtorno obsessivo-compulsivo (TOC) semelhante ao armazenamento compulsivo. O objetivo deste estudo é investigar qual classificação pode ser mais adequada para a CC. Para isso, adotamos duas abordagens: a primeira abordagem é a investigação das categorias diagnósticas para identificar as comorbidades psiquiátricas; a segunda abordagem refere-se as dimensões psicopatológicas em que comparamos impulsividade, sintomas obsessivo-compulsivos, instabilidade afetiva e armazenamento em pacientes com CC, TOC e TAB. Foram selecionados 80 pacientes (24 CC, 35 TOC e 21 TAB que não estivessem em mania nem hipomania) primeiramente foram avaliados de acordo com o SCID-CV e da seção especial para TCI e depois responderam os questionários de autopreenchimento. Realizamos duas análises: categorial e dimensional. Na análise categorial houve um equilibrio de associação entre os três grupos diagnósticos, e as comorbidades psiquiátricas apresentadas pelos três grupos diagnósticos foram congruentes com as descritas na literatura. Na análise dimensional os pacientes de CC apresentaram escores significativamente mais altos em todas as medidas de impulsividade e na aquisição, mas não nas outras sub-dimensões do armazenamento compulsivo, amontoamento e dificuldade em descartar. Pacientes bipolares pontuaram mais na dimensão mania da escala SCI-MOODS. Pacientes com TOC pontuaram mais nos sintomas obsessivo-compulsivos, e principalmente nas dimensões contaminação/lavagem e checagem da escala Pádua Inventory; no entanto, eles não apresentaram maior pontuação em nenhuma dimensão do armazenamento compulsivo. Um modelo discriminante foi construído com essas variáveis e classificou corretamente os pacientes de CC (79%), TOC (77%) e TAB (71%). Considerando os resultados da análise categorial cada um dos transtornos apresentou uma agregação categorial distinta, e na análise dimensional os pacientes com CC revelaram ter aquisição impulsiva, assemelhando-se aos TCI ao invés de TOC ou TAB. Sintomas maníacos foram bem distintos nos pacientes bipolares, assim como pacientes com TOC apresentaram mais obsessão e compulsão. Sintomas de armazenamento com exceção da aquisição não foram particularmente associados a qualquer grupo diagnóstico / Compulsive Buying (CB) is currently classified as an impulse control disorder not elsewhere classified (ICD). The prevalence of CB is estimated at around 5% of the general population and is identified with greater frequency in females. The chronic repetitive behavior and the behavior of spending wildly generates negative consequences to the individual, in addition to high rates of comorbidity with mood disorder, anxiety and other ICDs, which helps to maintain the existing disagreement on the classification of CB. It has been proposed that CB should be classified as an ICD, or as a sub-syndrome of bipolar disorder (BD), or as a variant of obsessive-compulsive disorder (OCD), similar to compulsive hoarding. The aim of this study is to investigate which classification is best suited for CB. For this, we adopt two approaches: the first approach is the investigation of the diagnostic categories to identify psychiatric comorbidities, the second approach refers to the psychopathological dimensions in which we compared impulsivity, obsessive-compulsive symptoms, affective instability and hoarding in patients with CB, OCD and BD. We selected 80 patients (24 CB, 35 OCD and 21 BD who were not in mania or hypomania) were first evaluated according to the SCID-CV and the special section to TCI, then answered the self-report questionnaires. We performed two analyses: categorical and dimensional. In categorical analysis, there was a balance of association between the three diagnostic groups, and psychiatric comorbidities by the three diagnostic groups were consistent with those described in the literature. In dimensional analysis of CB patients, there were significantly higher scores in all measures of impulsivity and the acquisition, but not in other sub-dimensions of the compulsive hoarding, clutter and difficulty discarding. Bipolar patients scored higher on the mania dimension from the SCI-MOODS scale. OCD patients scored higher on obsessive-compulsive symptoms, and, particularly, higher on the contamination/washing and checking dimensions from the Padua Inventory scale; however, they did not score higher on any hoarding dimension. A discriminant model built with these variables correctly classified patients of CB (79%), OCD (77%) and BD (71%). Considering the results of categorical analysis, each of the disorders presented a distinct clustering categorical, and dimensional analysis in patients with CB reported having impulsive acquisition, resembling the TCI instead of OCD or BD. Manic symptoms were distinctive of BD patients, and patients with OCD were distinctive obsession and compulsion. Hoarding symptoms other than acquisition were not particularly associated with any diagnostic group

Introdução: A Terapia Cognitivo-Comportamental (TCC) e os inibidores seletivos de recaptação de serotonina (ISRS) são considerados os tratamentos de primeira linha para o Transtorno Obsessivo-Compulsivo (TOC) nos ensaios clínicos randomizados (ECR). No entanto, a maior parte destes estudos exclui grande parte dos pacientes (em torno de 50%) por apresentarem comorbidades psiquiátricas. Ensaios clínicos pragmáticos e de efetividade, que costumam simular ambientes clínicos naturalísticos ao estudar amostras que representam melhor a população real comparando tratamentos ativos, são de grande importância para as decisões tomadas por um sistema de saúde e poucos têm sido feitos para avaliar a efetividade dos tratamentos para o TOC. O objetivo do presente estudo foi comparar os tratamentos de primeira linha para o TOC em uma amostra mais próxima da população que procura atendimento e avaliar características clínicas associadas às respostas aos tratamentos. Metodologia: Pacientes de 18 a 65 anos de idade, com escore de linha de base da YBOCS de pelo menos 16 para obsessões e compulsões, ou pelo menos 10 apenas para obsessões ou compulsões e com possíveis comorbidades psiquiátricas adicionais foram alocados seqüencialmente para tratamento de TCC em grupo (TCCG; n = 70) ou para tratamento medicamentoso (ISRS; n = 88). A TCCG consistiu em doze sessões semanais de duas horas cada com grupos de 6 a 8 pacientes, baseadas em um manual validado (Cordioli, 2002). O medicamento utilizado foi a fluoxetina com dosagem máxima de 80mg/dia. Foram analisadas respostas aos tratamentos como variáveis contínua (redução percentual na YBOCS) e categórica (redução de pelo menos 35% na YBOCS e ICG 1 muito melhor ou 2 melhor. Resultados: Os escores da YBOCS reduziram 23,13% no grupo tratado com TCCG e 21,54% no grupo tratado com ISRS, sem diferença estatística entre os grupos de tratamento (p = 0,875). Foi encontrada em 33,3% dos pacientes de TCCG e 27,7% dos pacientes de ISRS a redução de pelo menos 35% no escore da YBOCS e resposta à ICG 1 ou 2 (p = 0,463). O número médio de comorbidades psiquiátricas por paciente foi 2,7; e 81,4% da amostra apresentou pelo menos uma comorbidade. A redução na YBOCS foi significativamente menor entre os pacientes com uma ou mais comorbidade psiquiátrica (21,15% e 18,73%, respectivamente) do que entre os pacientes com TOC puro (34,62%) (p = 0,034). Sexo masculino, apresentar um escore inicial mais alto na Beck-A, ter abandonado o tratamento e apresentar comorbidade com Transtorno Depressivo Maior ou Distimia foram associados com taxas mais baixas de resposta ao tratamento, independente do tratamento recebido. Os resultados sugeriram que em uma população mais heterogênea os tratamentos de primeira linha para o TOC são menos efetivos. É necessário o desenvolvimento de intervenções que sejam efetivas para uma população da prática clínica / Introduction: Cognitive-Behavioral Therapy (CBT) and selective serotonin reuptake inhibitors (SSRI) are considered the first line treatments for Obsessive-Compulsive Disorder (OCD) in randomized controlled trials (RCT). However, most of these trials exclude a great amount of patients (around 50%) for presenting psychiatric comorbidities. Pragmatical and effectiveness clinical trials simulate natural clinical environments and compare active treatments in samples that represent the real population. These trials are of great importance for decision makers of the health public system, and only a few trials have investigated the effectiveness of treatments to OCD. The aim of this study was to compare the first line OCD treatments in a sample closer to the OCD real population, and to evaluate clinical characteristics associated to responses to treatments. Methodoly: Patients (1865 years; baseline Yale-Brown Obsessive-Compulsive Scale (YBOCS) scores 16; potentially presenting additional psychiatric comorbidities) were sequentially allocated for treatment with group CBT (GCBT; n=70) or pharmacological treatment (SSRI; n=88). GCBT consisted in twelve two hours weekly sessions with groups of 6 to 8 patients, based in a validated manual (Cordioli, 2002). Medication utilized in SSRI group was fluoxetine, 80mg/day. Response to treatment was analyzed as continuous variable (percent reduction on YBOCS) and as categorical variable (reduction of at least 35% on YBOCS and CGI 1 much better or 2 better. Results: Mean Y-BOCS scores fell by 23.13% in the GCBT and 21.54% in the SSRI group. Symptom reduction did not differ between groups (p = 0.875). A reduction of at least 35% in baseline Y-BOCS score and a CGI rating of 1 (much better) or 2 (better) was achieved by 33.3% of patients in the GCBT and 27.7% in the SSRI group (p=0.463). Patients presented 2.7 mean number of psychiatric comorbidity, and 81.4% showed at least one additional disorder. The YBOCS reduction was significantly lower in patients with one or more psychiatric comorbidities (21.15%, and 18.73%, respectively) than those with pure OCD (34.62%) (p = 0.034). Low responses to treatments were found to be associated to: being male, presenting a high initial Beck-A score, comorbid major depression, dysthymia and abandoning treatment, independently of the treatment received. The development of effective interventions to a real population is necessary

Introdução: Ao longo da história, as parafilias foram ora consideradas patologias, ora não consideradas. O Manual Diagnóstico e Estatístico de Transtornos Mentais (DSM-5) estabeleceu a distinção entre parafilias e Transtornos Parafílicos (TP), sendo que apenas os TP foram considerados doenças. Por outro lado, a associação entre sintomas obsessivos e parafilias já foi cogitada por muitos autores. Porém, a falta de melhores definições dos sintomas parafílicos dificultava tais estudos. Objetivos: Avaliar a presença de TP e/ou parafilias em mulheres e a possível associação com transtorno obsessivo-compulsivo (TOC) e/ou com transtorno de personalidade obsessivocompulsiva (TPOC). Casuística e Métodos: As alunas (N=190) foram avaliadas por meio de questionários anônimos e autorresponsivos de TOC, TPOC, parafilias e TP. Para o TOC foi utilizada a escala de Yale-Brown. Para as demais variáveis foram utilizadas escalas baseadas no DSM-5, segundo o qual indivíduos parafílicos com comportamentos exibicionistas, frotteuristas, voyeuristas e pedofílicos são considerados portadores de TP porque, por definição, seus impulsos são realizados com quem não consentiu ou não tem capacidade de consentir essas práticas sexuais. Porém, se o indivíduo preenche os critérios para estas parafilias e não tem o respectivo comportamento nem sofrimento, ele terá a respectiva parafilia, mas não o TP. Resultados: As fantasias parafílicas mais frequentes foram: pelo menos uma parafilia (53,2%), Voyeurismo (30,2%) e Fetichismo (25,4%). As parafilias mais frequentes foram: pelo menos uma parafilia (24,5%), Voyeurismo (9%) e Fetichismo (8,5%). Quanto aos TP, os mais frequentes foram: pelo menos um TP (13,8%), Voyeurista (6,9%), do Masoquismo (3,7%) e Frotteurista (3,7%). O TOC subclínico (Yale-Brown entre 8 e 15) foi estatisticamente significativo quando associado a fantasias parafílicas, enquanto o TOC (Yale-Brown >= 16) quando associado a parafilias e TP. O TPOC foi estatisticamente significativo quando associado a fantasias, parafilias e TP. Conclusões: A intensidade dos sintomas de TOC foi diretamente relacionada à intensidade dos sintomas parafílicos, enquanto que o TPOC foi relacionado a fantasias parafílicas, parafilias e TP. Devido a limitações metodológicas como a ausência de instrumentos padronizados validados, os resultados obtidos nesta pesquisa foram considerados traços de associação / Introduction: Throughout history, paraphilias have been at times considered pathologies or not. The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) established the distinction between paraphilias and Paraphilic Disorders (PD), with only PD considered as a disease. On the other hand, the association between obsessive symptoms and paraphilias has been considered by many authors. However, the lack of better definitions for paraphilic symptoms made such studies more difficult. Objectives: To assess the presence of PD and/or paraphilias in women and its possible association with obsessive-compulsive disorder (OCD) and/or with obsessive-compulsive personality disorder (OCPD). Case Series and Methods: Students (N=190) were assessed by means of anonymous, self-reported questionnaires on OCD, OCPD, paraphilias and PD. For OCD, the Yale-Brown scale was used. For the other variables scales based on DSM-5 were used, according to which paraphilic individuals with exhibitionistic, frotteuristic, voyeuristic, and pedophilic behaviors were considered as having PD, since, by definition, their impulses are carried out with non-consenting individuals or those unable to consent with such sexual practices. However, if the individual meets the criteria for such paraphilias but does not have the respective behavior or distress, he/she will have said paraphilia, but not PD. Results: The most frequent paraphilic fantasies were: at least one paraphilia (53.2 %), Voyeurism (30.2 %) e Fetishism (25.4 %). The most frequent paraphilias were: at least one paraphilia (24.5 %), Voyeurism (9 %) e Fetishism (8.5 %). As regard to PD, the most frequent were: at least one PD (13.8%), Voyeurist (6.9 %), of Masochism (3.7 %) and Frotteurist (3.7 %). Sub-clinical PD (Yale-Brown between 8 and 15) was statistically significant when associated with paraphilic fantasies, whereas OCD (Yale-Brown >= 16) when associated with paraphilias and PD. OCPD was statistically significant when associated with fantasies, paraphilias, and PD. Conclusions: The intensity of OCD was directly related to the intensity of paraphilic symptoms, whereas OCPD was related to paraphilic fantasies, paraphilias, and PD. The results point to traits of association between these clinical conditions, which recommends research in this direction

Obsessive-compulsive disorder (OCD) is a serious psychiatric condition manifested by repeated thoughts followed by stereotypic compulsive behavior. Alterations to cortico-thalamo-striato- cortical circuits are most often implicated in the pathophysiology of OCD. However, many studies have also found a changed volume, shape and activity of the hippocampus in OCD patients. This work focused on the activity of hippocampal CA1 cells during stereotypical checking behavior and on cognitive flexibility in a quinpirole (QNP) sensitization model of OCD. The activity of CA1 hippocampal cells during stereotypical checking was assessed in an enriched open-field test in QNP sensitized rats. Arc+ (activity-regulated cytoskeletal associated protein, or Arg 3.1) mRNA expression profiles were determined in CA1 coronal hippocampal sections following stereotypical checking. After the establishment of stereotypical checking (10 sessions), rats were exposed to the arena and sacrificed after 5 minutes. QNP sensitized animals visited the same objects with the same frequency as during previous sessions, while control rats did not. Locomotor activity was comparable between QNP treated rats and controls. Following sacrifice, rat brains were flash frozen and sliced to 20 µm thick sections. Sections, mounted on slides, were hybridized...

Syftet med denna uppsats är att ta reda på hur fem olika personer med OCD upplever framställningen av OCD i komediserien Scrubs samt dramafilmen The Aviator. Vidare togs det reda på varför intervjupersonerna upplever dessa framställningar som de gör och på vilka sätt de kan identifiera sig med dem. Studiens teoretiska ramverk är representationsteori, kodning och avkodning samt självkategoriseringsteori. Uppsatsens material består av kvalitativa intervjuer med fem olika intervjupersoner som alla har diagnosen OCD. Inför besvarandet av intervjufrågorna har intervjupersonerna tittat på avsnitt från Scrubs samt på filmen The Aviator där karaktärer med OCD finns med. Resultatet visar att fyra av fem intervjupersoner kan identifiera sig med fysiska tvångshandlingar som karaktären med OCD i Scrubs utför. Framställningen av OCD i The Aviator kan samtliga fem intervjupersoner identifiera sig med där majoriteten av dem identifierar sig i känslostämningen i form av stress, frustration och ångest som huvudkaraktären med OCD bitvis uppvisar. Den första slutsatsen är att intervjupersonerna upplever en mer adekvat framställning av OCD i The Aviator än i Scrubs, då framställningen i The Aviator innefattar en betydligt större del av det psykiska och känslomässiga lidande som OCD innebär. Den andra slutsatsen är att intervjupersonernas inställning till hur OCD framställs i Scrubs och The Aviator är beroende av den utsträckning i vilken de kan identifiera sig med detta.

Introduction: Obsessive-compulsive disorder (OCD) is a complex disorder that is associated with significantly impaired functioning. The current prevailing model of OCD implicates dysfunction of the serotonergic neurotransmitter system and fronto-striatal neural networks, but challenges in replicating findings within OCD samples are often attributed to clinical heterogeneity. OCD symptoms that develop or worsen within the perinatal period appears to reflect a distinct subtype of the disorder, but the genetic and neurobiological factors that contributes to its presentation in women is poorly understood. In this dissertation, we aimed to review the literature on the genetic architecture of OCD, identify potential gene candidates for perinatal OCD and analyze one serotonin system gene according to OCD and possible subtypes using meta-analytic techniques. Based on these findings, we then tested the association of serotonergic candidate gene polymorphisms with the presence of infant-related obsessive-compulsive symptoms (OCS). Lastly, we investigated the cortical morphological features associated with perinatal OCD and OCS symptom severity in postpartum mothers. Results: From prior reports in the literature and our own meta-analytic investigation, polymorphic variants in genes coding for the serotonergic transporter and serotonin 2A receptor subtype (SLC6A4 and HTR2A, respectively) appear to be candidates for perinatal OCD due to their association in female samples. However, upon investigation in our perinatal sample (n=107), we found no evidence to support the association of the 5-HTTLPR polymorphism of SLC6A4 with perinatal-related OCS, but larger samples are needed to confirm this finding. Due to technical challenges, the HTR2A polymorphism remains to be tested. Our novel whole-brain explorations revealed distinct cortical morphology associated with symptom worsening across the perinatal period, irrespective of diagnosis. Cortical parameters were not able to differentiate mothers with and without OCD; however, OCD mothers displayed positive correlations between cortical surface area and symptom severity in widespread regions, including the frontal, parietal, temporal and occipital cortex. Conclusions: Overall, this body of work aimed to fill the gap in the literature by exploring the possible genetic and cortical correlates of perinatal-related OCS and OCD. While 5-HTTLPR or HTR2A are candidates for perinatal OCD, it is not yet clear whether they increase susceptibility for the development of infant-related OCS in the perinatal period. Distinct cortical alterations in surface area appeared alongside OCS exacerbation in the postpartum period in regions that extend beyond the frontoparietal network. This suggests that additional neural networks may be contributing to symptom severity and that the cortical plasticity that occurs across the perinatal period may predispose women for risk of OCD. Future studies should continue to use a multiple perspective approach, that utilizes genetic and neurobiological techniques, in order to provide greater insight into the etiology of perinatal OCD. / Dissertation / Doctor of Philosophy (PhD) / Women are at greater risk for the development of mental illness in the time surrounding pregnancy and postpartum, known as the perinatal period. In the case of perinatal obsessive-compulsive disorder (OCD), mothers may experience unique worries in regard to their parenting or fears that their baby may be harmed. While these worries are common, they can become disruptive when persistent and impact the mother’s mood and ability to bond with the infant. Our current understanding of OCD includes the influence of genetic factors and brain changes, but little is understood about what factors may increase risk for OCD in the perinatal period. In this thesis, we aimed to review whether certain alterations within DNA segments, known as gene variants, may be linked to the development of OCD in females and if these gene changes, as well as differences in brain structures in postpartum mothers, are associated with OCD symptoms during the perinatal period. The genes we examined are important for regulating a chemical signaling substance in the brain known as serotonin. Based on our results, we did not find a relationship between serotonin gene variants and OCD symptoms in perinatal women. We also found no differences when comparing the cortical brain structures between mothers with OCD and healthy mothers; however, we observed that measures of surface area across several cortical brain regions were related to symptom worsening from pregnancy to postpartum, and also with symptom severity in postpartum mothers with OCD. These results suggest that there are widespread brain changes during the postpartum period that may increase a mother’s risk for developing OCD. Overall, the work in this thesis provides the first glimpse into potential risk factors for perinatal OCD.

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Metacognitive therapy (MCT) has been shown to be a promising treatment approach for obsessive-compulsive disorder (OCD). The changeability of metacognitions by (metacognitive) treatment and its relevance to treatment outcome is, however, still unclear. The current study investigates, (1) if treatment with MCT or exposure and response prevention (ERP) in a randomized-controlled pilot trial (n = 24 patients with OCD) changes OCD-specific metacognitions of thought fusion beliefs, beliefs about rituals and stop signals, and (2) if these changes are relevant for the treatment outcome in terms of patient- and therapist-rated OCD symptoms. ANOVA with pretest, posttest and follow-up scores could show that all three metacognitions significantly decreased during both treatments. Regarding thought fusion beliefs, a significant interaction effect indicated a higher decrease after MCT than ERP treatment. In hierarchical regression analyses, changes in stop signals from pre- to post-treatment significantly predicted patient-rating OCD symptoms at post-treatment and follow-up at 3 months after treatment. These changes were even predictive of post-treatment outcome after controlling for general metacognitions and dysfunctional cognitive beliefs. These findings support the assumption thatmetacognitions can change during both treatments and that changes in stop signals might be relevant for the treatment outcome on the symptom level in OCD.

Le trouble obsessionnel-compulsif (TOC) est un trouble anxieux fréquent et invalidant. Pour un grand nombre de patients, il existe une résistance aux thérapeutiques actuellement disponibles, soulignant toute l'importance de mieux préciser la physiopathologie du TOC. Le principal objectif de cette thèse est d’étudier les altérations anatomiques et fonctionnelles des voies thalamo-corticales intéressant le cortex orbitofrontal (COF) et le cortex cingulaire antérieur (CCA) dans le TOC. Pour cela, nous avons utilisé plusieurs outils complémentaires permettant d’appréhender cette problématique sous différents angles méthodologiques.Concernant les altérations anatomiques associées au TOC, nous avons rapporté les données de méta-analyses des études de neuro-imagerie volumétrique et morphométrique ainsi que les résultats d'une étude originale d'imagerie volumétrique. Une diminution du volume orbitofrontal, une augmentation du volume thalamique et une relation entre ces modifications de volumes ont été observées chez les patients avec TOC comparativement aux témoins. Les modifications de densité de matière grise concernaient le COF et le putamen dans le sens d'une augmentation et les cortex pariétal et préfrontal dorsolatéral dans le sens d'une diminution dans le TOC.Concernant les altérations fonctionnelles associées au TOC, nous avons détaillé un travail de méta-analyse des études d'imagerie fonctionnelle, un travail expérimental chez le primate basé sur des manipulations pharmacologiques intra-cérébrales, puis un travail expérimental chez l'homme reposant sur le développement d'une tâche comportementale originale couplée à l'imagerie fonctionnelle. Dans notre méta-analyse, nous avons décrit la participation fonctionnelle de régions comme le COF, le thalamus et le striatum lorsque des symptômes obsessionnels et compulsifs étaient provoqués chez des patients. Chez le primate subhumain, nous avons montré qu'une hyperactivation du noyau ventral-antérieur, par levée de l'inhibition GABAergique, entraînait l'apparition de comportements pseudo-compulsifs. Ensuite, à l'aide d'une tâche originale qui mettait les sujets en situation de vérifier, nous avons mis en évidence que les dysfonctions orbitofrontales associées au doute lors de la prise de décision n'étaient pas modulées ni par les informations contextuelles (signaux d'erreur), ni par la réponse comportementale chez les patients avec TOC comparativement à des sujets témoins.Enfin, la superposition des cartes morphométriques et fonctionnelles a trouvé une relation entre les altérations anatomiques et fonctionnelles au sein du COF. Nos résultats soulignent toute l'importance des voies thalamo-orbitofrontales dans la physiopathologie du TOC. / Obsessive-compulsive disorder (OCD) is a frequent and disabling anxiety disorder. Available treatments are effective for most patients but impairing residual symptoms and treatment resistance are common in OCD patients. Therefore, a better understanding of OCD pathophysiology is essential for further improvement of therapeutic strategies. The main goal of my thesis was to assess the anatomical and funtional thalamocortical alterations associated with OCD. Concerning the anatomical thalamocortical alterations associated with OCD, we conducted two meta-analyses of anatomical neuroimaging studies and an original volumetric neuroimaging study. We reported a smaller thalamic volume and a greater orbitofrontal volume, but also an inverse relationship between the volume changes in OCD patients compared with healthy subjects. Furthermore, we showed that gray matter density within the orbitofrontal cortex and the putamen were enhanced in OCD. Concerning the functional thalamocortical alterations associated with OCD, we reported data coming from a meta-analysis of functional neuroimaging studies, an experimental study in subhuman primates using local brain pharmacological manipulations and an event-related neuroimaging study in OCD patients. In our meta-analysis, we showed that the orbitofrontal cortex, the thalamus and the striatum were involved in the mediation of OCD symptoms. In subhuman primates, the pharmacologically induced overactivity within the ventralanterior thalamic nucleus leaded to the emergence of compulsive-like behaviors. Then, in our neuroimaging study, we found that doubt-related orbitofrontal dysfunctions were not modulated by neither error signals nor compulsive-like behaviors in OCD patients, compared with healthy subjects. Finally, we described by using meta-analytic data that anatomical and functional brain alterations overlap with the lateral orbitofrontal cortex in OCD. In conclusion, our results suggest that the thalamo-orbitofrontal network may play a primary role in the genesis and mediation of OCD symptoms.