A Depressão é um transtorno mental grave e com alta prevalência, de difícil tratamento e fator de risco para inúmeras outras doenças e disfuncionalidades. Seus principais sintomas são o humor deprimido e a anedonia. Considera-se que a personalidade afeta a vulnerabilidade individual para a depressão além de influenciar os tipos de sintomas e complicações experimentadas pelo paciente. O presente trabalho aborda o tema do Transtorno Depressivo Maior em relação a características de temperamento e caráter, baseado no modelo psicobiológico de Cloninger. Questiona-se quais estariam associadas à Depressão Maior e ainda, quais outras se revelam protetoras da saúde e do bem estar físico, mental e social. Foi realizado um estudo transversal cujo objetivo foi comparar características de temperamento e caráter entre sujeitos com Transtorno Depressivo Maior moderado a grave e um grupo controle de sujeitos saudáveis, sem transtornos neuropsiquiátricos. Os pacientes deprimidos estavam sem uso de antidepressivos há pelo menos três semanas no momento da avaliação. Participaram 103 sujeitos (69 mulheres e 34 homens) em cada grupo, pareados por sexo e idade. Os mesmos preencheram o Inventário de Temperamento e Caráter (ITC), um teste autoaplicável e que avalia quatro dimensões de temperamento (Busca de Novidades, Evitação de Danos, Dependência de Recompensa e Persistência) e três de caráter (Autodirecionamento, Cooperatividade e Autotranscendência), cada qual com suas subdimensões. Foi realizada a comparação de dados sociodemográficos entre os grupos e a correlação entre as 7 dimensões de temperamento e caráter com escalas que avaliam afeto e humor no grupo de deprimidos e outras características do Transtorno Depressivo Maior, como tipo, idade de início da Depressão e número de episódios depressivos. Foi realizada a comparação das médias com o teste-t e das frequências com o chi-quadrado. Correlações foram realizadas para analisar as diferentes variáveis com o coeficiente de correlação de Pearson e nível de significância em 5% e com o teste de correção Bonferroni, estabelecendo nível de significância 0,007 para a comparação das 7 dimensões e 0,002 para as 25 subdimensões. Os resultados mostraram que pacientes com depressão apresentaram um escore maior de Evitação de Danos (M=25,58, DP=7,15) e um escore menor de Autodirecionamento (M=21,65, DP=8,03) comparados ao grupo controle (M=15,39, DP=6,09; M=33,43, DP=5,89, respectivamente, p<0,001). Por outro lado, sujeitos do grupo controle, além do Autodirecionamento, apresentaram também escores maiores em Cooperatividade (M=34,14, DP=4,85) comparados aos pacientes com depressão (M=29,44, DP=6,93, p<0,001). Por ser um estudo transversal não foi possível abordar a questão de traço ou estado-dependência destas dimensões de personalidade na Depressão Maior / Depression is a severe mental disorder of high prevalence, difficult treatment and risk factor for several other diseases and disorders. Its main symptoms are depressed mood and the anhedonia or loss of interest. There is evidence that personality affects the individual vulnerability for depression, as well as influences the types of symptoms and complications experimented by the patient. This work investigated the relationship between Major Depressive Disorder and temperament and character traits, based on Cloninger`s psychobiological model. We investigated which traits may be associated to Major Depression; furthermore, which others may reveal themselves protective of health and physical, mental and social welfare. A cross-sectional study was performed with the objective of comparing temperament and character traits between subjects with moderate to severe Major Depressive Disorder and a control group composed of healthy subjects without neuropsychiatric disorders. The depressed patients were antidepressant-free for at least three weeks at the time of the assessment. One hundred and three subjects (69 women and 34 men) participated in each group, matched by gender and age. These individuals filled out the Temperament and Character Inventory (TCI), a self-administered test which evaluates four dimensions of temperament (Novelty Seeking, Harm Avoidance, Reward Dependence and Persistence) and three of character (Self-Directedness, Cooperativeness and Self- Transcendence), each one with their own subscales. A comparison of sociodemographic data between the groups and the correlation between the seven dimensions of temperament and character was performed. Scales were used to assess affect and mood in the group of depressed individuals, as well as other characteristics of the Major Depressive Disorder, such as type, age of depression onset and the number of depressive episodes. The means were compared with t-tests and frequencies with the chi-square test. Correlations were made to analyze the different variables with Pearson correlation coefficient and the significance level at 5% threshold. The Bonferroni correction test was also applied, establishing the significance level in 0.007 for the comparison of the 7 dimensions and 0.002 for the 25 subscales. The results showed that patients with depression presented a higher Harm Avoidance score (M=25,58, SD=7,15) and a lower Self-Directedness score (M=21,65, SD=8,03) when compared to the control group (M=15,39, SD=6,09; M=33,43, SD=5,89, respectively, p<0,001). On the other hand, subjects from the control group, as well as increased Self- Directedness, also had significantly higher scores on Cooperativeness (M=34,14, SD=4,85) compared to patients with depression (M=29,44, SD=6,93, p<0,001). As this is a crosssectional study, it was not possible to approach the matter of trace or state-dependency of these dimensions of the Major Depression Personality

O HCL-32 é um questionário de 32 itens, de auto-aplicação, onde os sintomas são avaliados através de respostas do tipo \"sim\" (presente ou típico) ou \"não\" (não está presente ou atípico). Além disso, o HCL-32 tem 8 seções para avaliar a gravidade e o impacto dos sintomas sobre os diferentes aspectos da vida do paciente. A pontuação é obtida pela soma das respostas positivas para os 32 itens sobre hipomania. A versão original do HCL-32 foi traduzido e adaptado para o português brasileiro. A primeira versão do HCL-32 foi traduzida por nós, revisados por especialistas em transtornos de humor, bem como por um professor de português brasileiro. Foi então retro-traduzida por um professor de inglês americano. Dos indivíduos inicialmente selecionados, foram excluídos 27, 11 devido à presença de comorbidades com abuso de substância, e 16 devido à incapacidade de preencher corretamente o questionário. Assim, nossa amostra final ficou composta por 81 pacientes com TB (37 TBI; 44TBII), 42 com TDM, e 362 sujeitos de uma população não clínica. A consistência interna foi elevada, com um alfa de Cronbach de 0,793 para todo o HCL-32 VB, indicando que os itens do questionário são suficientemente homogêneos. Indivíduos com TB tiveram a maior pontuação no HCL-32 VB. A média de respostas afirmativas foi significativamente diferente de acordo com o diagnóstico. Analisamos a capacidade em diferenciar os diagnósticos através da curva ROC. A área sob a curva foi de 0.702, indicando a boa capacidade da escala para distinguir entre diagnósticos. A melhor combinação de sensibilidade (0.75) e especificidade (0.58) ocorreu com uma pontuação acima de 18. Esta pontuação distinguiu entre pacientes com TB e TDM. Para comparar as propriedades discriminativas do HCL-32 VB e MDQ VB, foram calculadas a sensibilidade e especificidade de ambos os questionários. A HCL-32 VB teve uma sensibilidade de 0.75 e especificidade de 0.58. O MDQ teve sensibilidade de 0.70 e especificidade de 0.58. Assim, a HCL-32 BV apresentou maior sensibilidade, mas a mesma especificidade que o MDQ. A análise fatorial resultou em nove fatores com autovalores > 1, explicando 53,1% da variância total. De acordo com o teste Scree, foi preferida uma solução com três fatores. O primeiro fator, com autovalor de 4,90, explicou 15,3% da variância e foi composto por 10 itens. Essa subescala reflete questões relacionadas com ativação/elação. O segundo fator, com autovalor de 3,48 (10,88% da variância), composto por 11 itens e sua estrutura inclui questões relacionadas com \"irritabilidade / comportamento de risco\". O terceiro fator, com autovalor de 1,56 (4,87% da variância), ficou composto por cinco itens e sua estrutura reflete questões relacionadas com \"desinibição / ativação sexual. Os parâmetros psicométricos de HCL-32 VB sugerem que é um instrumento útil para a detecção de hipomania em pacientes com transtornos de humor. O HCL-32 VB é um questionário rápido de auto-aplicação e de fácil interpretação / The HCL-32 is a 32-item self-administered questionnaire where symptoms are assessed through yes (present or typical) or no (not present or untypical) answers. In addition, the HCL-32 has 8 other sections evaluating the severity and impact of the symptoms on different aspects of patient\'s life. The score is obtained by adding the positive responses to the 32 symptoms of hypomania. The original version of the HCL-32 was translated and adapted to Brazilian Portuguese .The first draft of the Brazilian version was translated by us, reviewed by experts in mood disorders, as well as by a Brazilian-Portuguese teacher. It was then back-translated by an English (American) teacher. Of the individuals initially enrolled, 27 individuals were excluded; 11 due to the presence of comorbidities with substance abuse, and 16 due to inability to properly fill the questionnaires. Accordingly, our final sample comprised of 81 patients with BP (37 BPI; 44 BPII), 42 with MDD, and 362 subjects from a nonclinical population. Internal consistency was high, with a Cronbach\'s alpha of 0.793 for the entire HCL-32 BV, indicating that the items of the questionnaire are sufficiently homogeneous. Individuals with BP had the highest HCL-32 BV scores. The mean number of affirmative responses to the list of symptoms was significantly different according to diagnosis. We analyzed the scale\'s discrimination for BP trough the ROC curve. The area under the curve was 0.702 indicating the good ability of this screening scale. The best combination of sensitivity (0.75) and specificity (0.58) happened with a score above 18. This score discriminates between BP patients and MDD. To compare the discriminative properties of HCL-32 BV and MDQ, we calculated the sensitivity and specificity of both questionnaires. The HCL-32 BV had a sensitivity of 0.75 and specificity of 0.58. The MDQ had sensitivity of 0.70 and specificity of 0.58. Hence, the HCL-32 BV showed higher sensitivity but the same specificity than the MDQ. The factor analysis resulted in 9 factors with eigenvalues > 1, explaining 53.1% of the total variance. According to the Scree test, a 3-factor solution was preferred. The first factor, with an Eigenvalue of 4.90, explained 15.3% of the variance and comprised 10 items . This subscales structure reflects questions related to active/elated symptoms. The second factor, with an Eigenvalue of 3.48 (10.88% of the variance), comprised 11 items and its structure includes questions associated with irritable/risk-taking items. The third factor, with an Eigenvalue of 1.56 (4.87% of variance), comprised 5 itens and its structure reflect questions related to disinhibition/activation sexual. The psychometric parameters of HCL-32 BV suggest it as a useful instrument for the detection of hypomania in patients with mood disorders. HCL-32 BV is a brief, self-administered questionnaire of easy application and interpretation

DNA methylation is necessary for learning, memory consolidation and has been implicated in a number of neuropsychiatric disorders. Obtaining high quality and comprehensive data for the three common forms of methylation in brain is challenging for methylome-wide association studies (MWAS). To address this we optimized a panel of enrichment methods for screening the brain methylome. Results show that these enrichment techniques approach the coverage and fidelity of the current gold standard bisulfite based techniques. Our MBD-based method can also be used with low amounts of genomic material from limited human biomaterials. Psychiatric disorders have high prevalence and are often chronic making them a leading contributor to disability. Major depressive disorder (MDD) has a lifetime prevalence of ~15% and high recurrence leading to substantial morbidity and costs to society. The underlying biological processes that contribute to MDD are poorly understood. Noting the importance of DNA methylation in neurobiology, we conducted the largest MWAS in human post-mortem brain uncover novel candidate genes and biomarkers associated with MDD. The top result of this MDD MWAS was within the gene ANKS1B. This gene has been implicated in many past genetic studies of psychiatric disorders and has experimental support as a regulator of neurotransmission. Targeted epigenetic editing technologies allow for precise modification of DNA methylation in living cells. However, an appropriate model system is critical to properly interpreting such experiments. An accelerated protocol for differentiating Ntera2 cells into human neurons was developed for this purpose. Ntera2-derived neurons express key neuronal markers and are well suited to use in epigenetic editing experiments. Concurrently, the generation of the reagents necessary for recapitulating the aberrant methylation at ANKS1B linked to MDD was undertaken. Using a modified CRISPR/Cas9 approach demethylating enzyme was directed to target sites to attempt perform editing of DNA methylation. Results indicate that significant but biologically irrelevant changes to methylation at ANSK1B were achieved. The novelty of the technology employed presented challenges to the success of the current work. However, the field of epigenetic editing is advancing rapidly and will remain an attractive method for functional characterization of future MWAS findings and basic neuroscience research.

Background and objectives: Whilst Active and Receptive Music Therapy techniques have been widely researched and are employed within a range of contexts and with diverse client populations, this study reports on their specific qualitative musical and verbal affordances in major depressive disorder and schizophrenia-spectrum psychotic disorders. The study also describes and compares the respective and joint contributions of the music therapy techniques in giving rise to the affordances as well as reporting on the similarities and differences within and between diagnostic groups. This is the first study of its kind within the South African context. Methods: A qualitative research approach using a case study design, sampled purposefully twenty patients of the above mentioned diagnostic groups for participation in this study comprising a course of eight twice weekly music therapy sessions. The primary data sources were transcribed video recordings of therapy sessions and an individual in-depth semi-structured interview after the course of therapy. Clinical session notes served as a corroborative data source. In-depth content and thematic analysis explored and compared qualitative affordances during music therapy comprising active and Receptive Music Therapy techniques. The qualitative affordances under investigation were i) musical qualities, and ii) verbal expressions. Emerging from these affordances were the respective and combined affordances of the music therapy techniques as well as the similarities and differences between the diagnostic groups. Findings: Thirteen themes emerged from the analysis of clients' verbatim verbal responses to both active music making and Receptive Music Therapy techniques. These themes are: i) not to feel; ii) to do or not to do; iii) grappling with the desired future; iv) hurt and fear of undesirable outcomes; v) sadness, brokenness and futility; vi) anger, trust and vulnerability; vii) desire for connection with and affection of others; viii) barricaded from being present, now; ix) tensing and un-tensing; x) personal relating to one’s musical expression; xi) reflections on the music and music making in therapy; xii) resilience and courage and xiii) invigoration and liberation. The Active Music Therapy techniques comprising clinical improvisation, structured musical exercises, drumming, vocal work, songwriting and movement, gave rise to ten themes expressing the musical affordances. The themes that emerged were i) reciprocal responding; ii) the explicit use of symbols through music; iii) regularity; iv) disturbance and difficulty; v) turning points; vi) energy bursting or lacking; vii) bodily synchrony; viii) intensified emotional expression; ix) exploring new territory and Active Music Therapy techniques comprising clinical improvisation, structured musical exercises, drumming, vocal work, songwriting and movement, gave rise to ten themes expressing the musical affordances. The themes that emerged were i) reciprocal responding; ii) the explicit use of symbols through music; iii) regularity; iv) disturbance and difficulty; v) turning points; vi) energy bursting or lacking; vii) bodily synchrony; viii) intensified emotional expression; ix) exploring new territory and x) resolution and arrival. The emerging themes express the extent of musical and verbal expression of all clients representing both diagnostic groups. Most saliently among clients with depression the affordances were the themes on accessing creativity, accessing and articulating internal feelings, experiencing resilient parts of self, reflecting on and integrating symbolic material, motivation to act and extending musical and verbal expression during social interaction. Among clients suffering from schizophrenia spectrum disorder, the most striking affordances were experiences of regularity and flow within disorganization, orientation to ‘here and now’ experiences through active music making and working with symbolic material expressed on a continuum of concrete to abstract. Clients from both diagnostic groups experienced a reduction in unwanted symptoms as expressed through increased energy levels, experiences of pleasure in music making and spontaneous musical and verbal self-expression. Conclusion: This study revealed qualitative affordances of specific music therapy techniques expressed through verbal content and musical qualities. These showed responses within a therapeutic relationship that express inter- and intra-personal connection, give voice to what is not always verbally accessible and facilitate multi-sensory, creative experiences, increased motivation, emotional expression, and the reclamation of energy, spontaneity and resilience. / Thesis (PhD)--University of Pretoria, 2017. / Psychiatry / PhD / Unrestricted

La dépression chez les jeunes est fréquente et entraîne une détresse et un handicap pour les individus et leurs familles/aides-soignants. Les lignes directrices en matière de traitement et de prévention soulignent la nécessité d'informations de qualité et d'interventions psychosociales fondées sur des données probantes. Récemment, on s'intéresse de plus en plus aux interventions psychopédagogiques, qui fournissent généralement des informations précises sur les problèmes de santé et sur l'auto-gestion au client et à ses aides-soignants. L'objectif de cette revue systématique est de déterminer si les interventions psychopédagogiques peuvent être utilisées pour prévenir et traiter la dépression chez les jeunes adultes. Des recherches systématiques ont été effectuées dans MEDLINE Ovid, PsycInfo, et les listes de références. Aucune étude ne répondait aux critères d'inclusion de cette revue. Quatorze études issues d'une édition spéciale du Psychiatric Rehabilitation Journal (Davis et al., 2018) ont été discutées. Ce numéro met l'accent sur les besoins et les services efficaces pour les personnes souffrant de graves problèmes de santé mentale pendant leur transition vers l'âge adulte. Les populations ciblées par ces études sont les suivantes : les étudiants universitaires bénéficiant d'un soutien éducatif, les jeunes adultes blancs et latino- américains bénéficiant d'une aide pour trouver un emploi, les jeunes et les jeunes adultes impliqués dans le système judiciaire, les jeunes adultes souffrant de troubles de l'humeur et les prestataires de services destinés aux jeunes en transition vers l'âge adulte. L'accent mis sur la diversité des échantillons met en lumière certains des progrès réalisés dans le domaine. Les interventions psychopédagogiques peuvent jouer un rôle dans la prévention et la prise en charge de la dépression chez les jeunes, en tant qu'approche principale ou complémentaire. Le nombre limité d'études, le manque d'hétérogénéité dans les formats et les évaluations, ainsi que le manque de cohérence dans la définition des interventions psychopédagogiques rendent difficile la comparaison des programmes et la mesure de l'efficacité globale. Les études futures doivent établir une définition commune des interventions psychopédagogiques, développer/évaluer les interventions psychopédagogiques conformément aux cadres d'interventions complexes et analyser leurs composantes actives. / Youth depression is common and leads to distress and impairment for individuals and their families/caregivers. Treatment and prevention guidelines stress the need for good information and evidence-based psychosocial interventions. Increasingly, there is a growing interest in psychoeducational interventions (PIs), which broadly deliver accurate information about health issues and self-management to the client and his/her caregivers. The aim of this systematic review is to investigate whether psychoeducational interventions can be used to prevent and treat youth depression. Systematic searches were undertaken in MEDLINE Ovid, psycINFO, and reference lists. No studies met the inclusion criteria for this review. Fourteen studies from a special edition of the Psychiatric Rehabilitation Journal (Davis et al., 2018) were discussed. This issue focuses on the needs of, and effective services for individuals with serious mental health conditions as they transition into adulthood. The populations of focus in these studies are: college students receiving educational supports, White and Latino young adults receiving employment supports, youth and young adults with justice system involvement, young adults with mood disorders, and service providers for youth in transition to adulthood. The focus on diverse samples highlights some of the progress in the field. PIs can have a role in preventing and managing youth depression, as a primary or complementary approach. The limited number of studies, heterogeneity in formats and evaluation, and inconsistent approach to defining PI, make it difficult to compare programmes and measure overall effectiveness. Future studies need to establish an agreed definition of PI, develop/evaluate PIs in line with frameworks for complex interventions, and analyse their active components.

Thèse de doctorat présenté en vue de l'obtention du doctorat en psychologie - recherche intervention, option psychologie clinique (Ph.D) / Les biais cognitifs sont des tendances qu’ont les individus à traiter l’information d’une certaine manière. Le terme biais réfère au fait que ces tendances sont souvent répétitives et rigides. Bien que l’on retrouve des biais cognitifs chez tous les individus, certains sont plus spécifiquement liés à la psychose et pourraient expliquer certains symptômes liés aux troubles psychotiques. Le premier objectif de cette thèse est d’examiner le niveau de preuve, ainsi que la taille de l’effet de l’association entre les biais de raisonnement et d’interprétation et les caractéristiques psychotiques (troubles psychotiques, symptômes psychotiques, expériences psychotiques sous-cliniques (psychotic-like experiences) et le risque de développer une psychose (psychosis risk)) ainsi que le niveau de preuve et la taille de l’effet des interventions psychologiques sur les biais cognitifs auprès de personnes ayant des caractéristiques psychotiques. Le deuxième objectif est d’explorer les biais cognitifs de manière transdiagnostique chez les individus ayant un trouble psychotique ou un trouble dépressif majeur. La première étude est une méta-revue portant sur les biais cognitifs associés aux caractéristiques psychotiques, et sur l’effet des interventions psychologique sur la modification des bais cognitifs. Cent-vingt-trois résultats provenant de quinze méta-analyses ont été évalués à l’aide du système Grading of Recommendations, Assessment, Development and Evaluations (GRADE; Gotlib, 2010). Les résultats ont montré qu’un niveau de preuve modéré à élevé soutenait les liens en des caractéristiques psychotiques et certains biais cognitifs, notamment : les biais d’interprétation lorsque étudiés regroupés, l’externalisation des événements cognitifs, le biais d’autoprotection (self-serving bias), l’attribution d’intentions hostiles, la saillance aberrante, le biais d’inflexibilité cognitive ou (belief inflexibility bias) (lorsque mesuré avec Maudsley Assessment of Delusions Schedule (MADS ; Wessely et al., 1993) et le biais de sauter aux conclusions (jump to conclusions) lorsqu’étudiées avec des tâches expérimentales (le biais de la collecte de données (data-gathering bias)). Les autres biais étudiés par les méta-analyses incluses dans la méta-revue ne sont pas soutenus par un niveau de preuve suffisante (le biais de personnalisation (personalizing bias), le biais contre les indices infirmatoires (bias against disconfirmatory evidence ; BADE), le biais contre les indices confirmatoires (bias against confirmatory evidence ;BACE), et le biais d’acceptation libérale (liberal acceptance bias)). Certains biais cognitifs étaient notamment liés aux symptômes similaires à la psychose chez des personnes en santé et chez des personnes à risque élevé de psychose. Un niveau de preuve modéré-élevé soutient un petit effet de taille des interventions psychologiques sur les biais cognitifs. La deuxième étude est une validation francophone du CBQp. Le questionnaire a été traduit et validé auprès de personnes ayant un trouble psychotique (N=30), un trouble dépressif (N=32) et dans un groupe normatif (N=663). Une analyse transdiagnostique par regroupements hiérarchiques de profils de biais cognitifs a également été réalisée. Nos résultats ont révélé une structure factorielle similaire à celle des auteurs originaux, avec la solution à un facteur (évaluation d’un score de biais cognitifs global) étant la meilleure, mais les solutions à deux facteurs (évaluation de biais divisés en deux thèmes liés à la psychose) et cinq facteurs (évaluation de cinq biais cognitifs différents) étaient les plus intéressantes cliniquement. Finalement, une solution à six regroupements a émergé de l’analyse par regroupements hiérarchiques, suggérant que des individus ayant des diagnostics similaires peuvent avoir des profils de biais cognitifs différents, et que des individus ayant des diagnostics différents peuvent avoir des profils de biais cognitifs similaires. Davantage d’études et de méta-analyses sont nécessaires pour mieux identifier les liens entre certains biais cognitifs et les caractéristiques psychotiques pour lesquels il n’y a aucune méta-analyse sur des échantillons cliniques, tels que le biais d’attribution d’intentions hostiles (hostility attribution bias), la saillance aberrante et le biais de sauter aux conclusions (lorsque mesurés avec des questionnaires autorapportés). D'autres biais étudiés par des méta-analyses chez des populations cliniques (par exemple, le biais de personnalisation, le biais contre les indices infirmatoires, le biais contre les indices confirmatoires et le biais d'acceptation libérale) doivent encore faire l'objet de recherches supplémentaires de qualité avant de pouvoir conclure sur leur relation avec les caractéristiques psychotiques. Une méta-analyse clarifiant les biais cognitifs spécifiques qui sont altérés par des interventions cognitives (spécifiques également) pourrait nous aider à mieux comprendre les composantes les plus efficaces des interventions sur les différents biais cognitifs, et ainsi améliorer les interventions actuelles. Les associations entre différents biais cognitifs et les symptômes similaires à la psychose dans les études analogues suggèrent également que d’autres groupes populationnels pourraient bénéficier d’interventions ciblant les biais cognitifs, la présence de ces biais et symptômes se retrouvant sur un spectre. Finalement, les résultats de notre deuxième étude nous laissent croire qu’il serait intéressant d’évaluer la présence de différents biais cognitifs de manière transdiagnostique à l’aide d’autres instruments de mesure. Notre version francophone du questionnaire de biais cognitifs pour la psychose pourra être utilisée auprès de populations francophones. / Cognitive biases are individual tendencies to process information in a certain way. The term bias refers to the fact that these tendencies are often rigid and repetitive. Although cognitive biases are found in all individuals, some are more specifically related to psychosis and may explain some of the symptoms associated with psychotic disorders. The first aim of this thesis is to examine the quality of evidence and effect size of the association between reasoning and interpretation biases and psychotic features (psychotic disorders, psychotic symptoms, psychotic-like experiences and psychosis risk) as well as the quality of evidence and effect size of psychotic interventions on cognitive biases in individuals with psychotic features. The second objective is to explore cognitive biases transdiagnostically in individuals with a psychotic disorder or a major depressive disorder. The first study is a meta-review on cognitive biases associated with psychotic features, and on the effects of psychological interventions on cognitive biases. One hundred and twenty-three outcomes from 15 meta-analyses were assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE; Gotlib, 2010). The results showed that moderate to high-quality evidence supported links between psychotic features and certain cognitive biases, namely: interpretation biases when studied together, the externalization of cognitive events, the self-serving bias, the hostility attributions bias, the aberrant salience bias, belief inflexibility bias (when measured with Maudsley Assessment of Delusions Schedule (MADS; Wessely et al., 1993) and the jumping to conclusion bias when measured with experimental tasks (the data-gathering bias). The other biases studied by the meta-analyses included in the meta-review are not supported by sufficient quality of evidence (the personalizing bias, the bias against disconfirmatory evidence, the bias against confirmatory evidence, and the liberal acceptance bias). Some cognitive biases were notably related to psychosis-like symptoms in healthy people and in people at high risk of psychosis. Moderate-high-quality evidence supports a small effect size of psychological interventions on cognitive biases. The second study is a French validation of the CBQp. The questionnaire was translated and validated with people with a psychotic disorder (N=30), a depressive disorder (N=32) and in a normative group (N=663). A cross-diagnostic analysis by hierarchical clustering of cognitive bias profiles was also performed. Our results showed a similar factor structure to that of the original authors, with the one-factor solution (assessment of a global cognitive bias score) being the strongest, but the two-factor (assessment of biases divided into two psychosis-related themes) and five-factor (assessment of five different cognitive biases) solutions being the most clinically interesting. Finally, a six-cluster solution emerged from the hierarchical cluster analysis, suggesting that individuals with similar diagnoses may have different cognitive bias profiles, and that individuals with different diagnoses may have similar cognitive bias profiles. More studies and meta-analyses are needed to better understand links between certain cognitive biases and psychotic features, including the hostility attribution bias and the aberrant salience, and the jump to conclusions bias when measured with self-report questionnaires, for which there is no meta-analysis in clinical studies. Other biases studied reviewed by meta-analyses on clinical populations (e.g. the personalizing bias, the bias against disconfirmatory evidence, the bias against confirmatory evidence, and the liberal acceptance bias) still need further quality research before being able to conclude about their relation with psychotic characteristics. A meta-analysis of the effect of specific psychological interventions on the different cognitive biases targeted by them could also help us to identify which specific interventions are effective on the different cognitive biases, and thus improve current interventions. Associations between different cognitive biases and psychosis-like symptoms in non-clinical studies also suggest that other population groups may benefit from interventions that have been developed to target cognitive biases, as the presence of these biases and symptoms occur across a spectrum. Finally, the results from our second study suggest that it would be interesting to assess the presence of different cognitive biases transdiagnostically using other measurement instruments. Our French version of the cognitive bias questionnaire for psychosis is now available to be used with French-speaking populations.

Background: The concept of alexithymia is characterized by difficulties identifying and describing one’s emotions. Alexithymic individuals are impaired in the recognition of others’ emotional facial expressions. Alexithymia is quite common in patients suffering from major depressive disorder. The face-in-the-crowd task is a visual search paradigm that assesses processing of multiple facial emotions. In the present eye-tracking study, the relationship between alexithymia and visual processing of facial emotions was examined in clinical depression. Materials and Methods: Gaze behavior and manual response times of 20 alexithymic and 19 non-alexithymic depressed patients were compared in a face-in-the-crowd task. Alexithymia was empirically measured via the 20-item Toronto Alexithymia-Scale. Angry, happy, and neutral facial expressions of different individuals were shown as target and distractor stimuli. Our analyses of gaze behavior focused on latency to the target face, number of distractor faces fixated before fixating the target, number of target fixations, and number of distractor faces fixated after fixating the target. Results: Alexithymic patients exhibited in general slower decision latencies compared to non-alexithymic patients in the face-in-the-crowd task. Patient groups did not differ in latency to target, number of target fixations, and number of distractors fixated prior to target fixation. However, after having looked at the target, alexithymic patients fixated more distractors than non-alexithymic patients, regardless of expression condition. Discussion: According to our results, alexithymia goes along with impairments in visual processing of multiple facial emotions in clinical depression. Alexithymia appears to be associated with delayed manual reaction times and prolonged scanning after the first target fixation in depression, but it might have no impact on the early search phase. The observed deficits could indicate difficulties in target identification and/or decision-making when processing multiple emotional facial expressions. Impairments of alexithymic depressed patients in processing emotions in crowds of faces seem not limited to a specific affective valence. In group situations, alexithymic depressed patients might be slowed in processing interindividual differences in emotional expressions compared with non-alexithymic depressed patients. This could represent a disadvantage in understanding non-verbal communication in groups.

Genome-wide association studies (GWASs) have reported numerous associations between risk variants and major psychiatric disorders (MPDs) including schizophrenia (SCZ), bipolar disorder (BPD), major depressive disorder (MDD) and others. We reviewed all of the published GWASs, and extracted the genome-wide significant (p<10) and replicated associations between risk SNPs and MPDs. We found the associations of 6 variants located in 6 genes, including L type voltage-gated calcium channel (LTCCs) subunit alpha1 C gene (), that were genome-wide significant ( ) and replicated at single-point level across at least two GWASs. Among them, the associations between MPDs and rs1006737 within are most robust. Thus, as a next step, the expression of the replicated risk genes in human hippocampus was analyzed. We found had significant mRNA expression in human hippocampus in two independent cohorts. Finally, we tried to elucidate the roles of venlafaxine and ω-3 PUFAs in the mRNA expression regulation of the replicated risk genes in hippocampus. We used cDNA chip-based microarray profiling to explore the transcriptome-wide mRNA expression regulation by ω-3 PUFAs (0.72/kg/d) and venlafaxine (0.25/kg/d) treatment in chronic mild stress (CMS) rats. ω-3 PUFAs and venlafaxine treatment elicited significant up-regulation. We concluded that might confer the genetic vulnerability to the shared depressive symptoms across MPDs and CACNA1C might be the therapeutic target for depressive endophenotype as well.

No description available.

Environ 300 millions de personnes dans le monde souffrent de dépression et environ 30% vont développer une dépression réfractaire. Une dépression est réfractaire quand deux traitements antidépresseurs ou plus échouent à améliorer la condition d’un patient. La stimulation magnétique transcrânienne (TMS) est un traitement sécuritaire et efficace de la dépression réfractaire. Son efficacité et sa tolérabilité ont été largement prouvées grâce à des études randomisées, des méta-analyses et des revues de littérature. Toutefois, jusqu’à présent, le traitement de la dépression réfractaire avec la TMS demeure sous-étudié avec des données en pratique clinique réelle. Pour répondre à cette lacune, nous avons conduit une analyse rétrospective des dossiers médicaux de patients dépressifs réfractaires ayant suivi un traitement de TMS à l’Unité de Neuromodulation Psychiatrique (UNP) du Centre Hospitalier de l’Université de Montréal (CHUM) entre janvier 2012 et mai 2022. Nous avons examiné l’efficacité et la tolérabilité de la TMS pour ces patients. De façon secondaire, nous avons vérifié si des caractéristiques cliniques des patients avant leur traitement de TMS pouvaient être associées avec l’amélioration de leurs symptômes dépressifs à la suite du traitement de TMS. Nous avons également vérifié si nos résultats étaient semblables à ceux retrouvés dans la littérature scientifique. Cette étude offrirait aux cliniciens une perspective réaliste de l’efficacité et de la tolérabilité de la TMS à une clinique de troisième ligne. / Around 300 million people worldwide suffer from depression and around 30% will develop treatment-resistant depression (TRD). Depression is treatment-resistant when two or more antidepressant treatments fail to improve a patient’s condition. Transcranial magnetic stimulation (TMS) is a safe and effective treatment for TRD. Its efficacy and tolerability have been widely demonstrated through randomized studies, meta-analyses, and literature reviews. However, to date, the treatment of TRD with TMS remains under-studied with evidence in real-world clinical practice. To address this gap, we conducted a retrospective chart review of TRD patients who had undergone TMS therapy at the Psychiatric Neuromodulation Unit (UNP) of the University of Montreal Hospital Center (CHUM) between January 2012 and May 2022. We examined the efficacy and tolerability of TMS for these patients. As a secondary measure, we examined whether baseline clinical characteristics of patients could be associated with the improvement of their depressive symptoms following TMS treatment. We also examined whether our results were similar to those found in the scientific literature. This study would provide clinicians with a realistic perspective on the efficacy and tolerability of TMS at a third-line clinic.