Evidências apontam para forte relação independente entre maus tratos na infância, comportamentos disruptivos e prejuízos em funções executivas. No entanto, ainda não é completamente compreendido como estes três fatores se relacionam entre si. Esta pesquisa avaliou a relação entre maus-tratos na infância e transtornos do comportamento disruptivo, testando desempenho em funções executivas como possível mediador e moderador desta relação. A presente pesquisa está inserida no estudo \"Coorte de escolares de alto risco para o desenvolvimento de psicopatologia e resiliência na infância e adolescência - projeto Prevenção\", projeto integrante do Instituto Nacional de Ciência e Tecnologia de Psiquiatria do Desenvolvimento para Infância e Adolescência (INCT-INPD), o qual incluiu 2500 crianças em idade escolar de São Paulo e Porto Alegre (Brasil). As crianças foram extensamente avaliadas com entrevistas diagnósticas, relatos de pais e da própria criança sobre maus tratos e com testes neuropsicológicos. Resultados indicam associação de maus tratos na infância e transtornos do comportamento disruptivo, porém não foi encontrada associação entre maus tratos e funções executivas. Crianças com transtornos do comportamento disruptivo apresentaram pior desempenho em teste específico para avaliação de flexibilidade cognitiva. Desempenho em funções executivas não agiu como mediador ou moderador da associação entre maus tratos e transtornos do comportamento disruptivo. Desta forma, os resultados indicam que a associação entre experiências de maus tratos e transtornos do comportamento disruptivo ocorre independentemente do desempenho em funções executivas. Futuros estudos longitudinais são fundamentais para confirmar estes resultados e elucidar os mecanismos cognitivos envolvidos nesta associação causal / Empirical evidences point to a strong independent relationship between maltreatment in childhood, disruptive behaviors and impairments in executive functions. However, how these three factors are interrelated it is not completed understood yet. This study evaluated the relationship between childhood maltreatment and disruptive behavior disorders, testing performance in executive functions as possible mediator and moderator factor in this relationship. This research is part of the study \"Cohort of high-risk students for the development of psychopathology and resilience in childhood and adolescence - Prevention Project\", a member project of the National Institute of Science and Developmental Psychiatry Technology for Children and Adolescents (INCT -INPD) in which is included 2,500 schoolchildren from São Paulo and Porto Alegre (Brazil). The children were evaluated with diagnostic interviews, reports of parents and children themselves about maltreatment and with neuropsychological tests, which included evaluation of inhibitory control, working memory, cognitive flexibility and planning. Results indicate association of childhood maltreatment and disruptive behavior disorder, but no association was found between maltreatment and executive functions. Children with Disruptive Behavior Disorders showed worse performance in specific task for assessment of cognitive flexibility. Performance in executive functions didn\'t work as a mediator or modifier variable in the association between childhood maltreatment and disruptive behavior disorder. Thus, the study results indicate that the association between experiences of maltreatment and disruptive behavior disorder occurs regardless of the performance in executive function in a community sample. Future longitudinal studies are essential to confirm these findings and elucidate the cognitive mechanisms involved on this causal association

<p>This dissertation evaluated the complex inter-relatedness between co-occurring childhood maltreatment exposures, physical intimate partner violence (perpetration and victimization), substance use frequency, and molecular genetics for substance use, utilizing appropriate developmental models and theoretical approaches. Three studies were proposed within this dissertation. Data for the three studies come from a national longitudinal panel study: The National Longitudinal Study of Adolescent to Adult Health (Add Health; Harris, 2013). Across studies, latent profile analysis was used to evaluate co-occurring childhood maltreatment exposures based on type and severity of exposures, which resulted in three homogenous sub-groups. The first sub-group was composed of individuals that had high levels of physical abuse exposure and moderate levels of childhood neglect and emotional abuse exposures (high physical abuse sub-group). The second sub-group (high sexual abuse sub-group) included individuals with high severity of sexual abuse exposure and moderate severity of all other childhood maltreatment types (i.e., physical abuse, emotional abuse, and neglect). This second sub-group was, therefore, the most vulnerable in terms of their childhood maltreatment exposure. A final normative sub-group was also found that included a majority of individuals with low severity of childhood maltreatment exposure across types. Additionally, across all three studies, a probabilistic multifaceted genetic risk score (i.e., polygenic risk score) was created to evaluate substance use related genetic risk. The first study evaluated the role of co-occurring childhood maltreatment exposure on substance use development from adolescence to young adulthood while evaluating substance use related genetic moderation. Generalized estimating equations were used to test the proposed model in study 1. Findings suggest that the high physical abuse sub-group was more susceptible to genetic risk and had increases in substance use frequency only at high levels of genetic risk. In contrast, for the high sexual abuse sub-group, childhood maltreatment and environmental exposures were more ubiquitous for substance use development from adolescence to young adulthood. To elaborate, the high sexual abuse sub-group demonstrated increases in substance use from adolescence to young adulthood irrespective of genetic risk. In study 2, substance use frequency in young adulthood was tested as a mechanism between childhood maltreatment sub-groups and subsequent physical intimate partner violence perpetration in adulthood. Once again, genetic moderation for the direct association between childhood maltreatment sub-groups and substance use frequency in young adulthood was tested within the larger mediation model. In study 3, physical partner violence victimization in young adulthood was tested as a mediator of the association between childhood maltreatment sub-groups and substance use frequency in adulthood. In study 3, in addition to the above-mentioned genetic risk score, an additional substance use related dopamine polygenic risk score was also tested. Specifically, in study 3, genetic moderation by both genetic risk scores was tested on 1) the direct pathway from childhood maltreatment sub-groups to substance use frequency in adulthood, and 2) the direct pathway from physical intimate partner violence victimization in young adulthood to substance use frequency in adulthood. In both studies 2 and 3, product of co-efficient method was used to estimate mediation hypothesis, and moderated-mediation models were used to test for genetic moderation within the mediation model. Research aims for studies 2 and 3 were largely not supported. However, supplementary models indicate that substance use frequency may not be a causal mechanism but may be a contextual factor exacerbating the association between childhood maltreatment exposures and physical intimate partner violence perpetration. Implications for findings are discussed in detail. </p>

Religiosity is adopting a belief system surrounding concepts of purpose, meaning, and value through an institution that has already defined these concepts prior to the individual member attending and that member’s degree of participation. Religiosity does have protective factors against negative health outcomes. This protective influence was evaluated in this study. Data from Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions were examined to learn about the relationship between protective effects of religious participation on substance abuse, and whether this association weakened for individuals who have experienced higher levels of childhood abuse. A binary logistic regression was completed to examine this relationship. Religiosity does decrease the likelihood of experiencing an opioid use disorder for lower levels of childhood maltreatment, but only slightly. In extreme cases of sexual, emotional, and physical abuse, religiosity does not decrease the likelihood of experiencing an opioid use disorder.

Objectif : Cette étude vise à déterminer si : les traumatismes en enfance sont liés à l’attachement (anxiété d’abandon, évitement de l’intimité) et à la régulation émotionnelle et si ces variables sont liées à des difficultés d’adaptation (détresse, résilience, symptômes psychologiques) à une rupture amoureuse non-désirée chez des jeunes adultes ; et si l’attachement et la régulation émotionnelle servent de médiateurs entre les traumatismes à l'enfance et l'adaptation à la rupture. Méthode : Les traumatismes, l’attachement, la régulation émotionnelle et l'adaptation à la rupture ont été évalués dans un échantillon de 303 étudiants universitaires ayant vécu une rupture récente. Des analyses acheminatoires ont été effectuées. Résultats : La détresse est associée directement à l’anxiété d’abandon (p < ,01), la dérégulation (p < ,05) et la régulation émotionnelle (p < ,01). Les symptômes psychologiques sont associés directement aux traumatismes (p < ,01), à l’anxiété d’abandon (p < ,01), à la dérégulation (p < ,01) et la régulation émotionnelle (p < ,05). La résilience est directement associée aux traumatismes, à l’évitement de l’intimité, à la régulation émotionnelle (p < ,01) ainsi qu’à la dérégulation émotionnelle (p < ,05). Les traumatismes sont indirectement associés à la détresse (p < ,01), à la résilience (p < ,01) et aux symptômes psychologiques (p < ,01) par le biais de l’anxiété d’abandon, l’évitement de l’intimité, la régulation et dérégulation émotionnelle. Conclusion : Les jeunes ayant vécu des traumatismes à l'enfance et ayant vécu une rupture pourraient bénéficier d'interventions visant à améliorer les insécurités d’attachement et les compétences de régulation émotionnelle. / Aim: This study aimed to investigate whether: 1) childhood maltreatment is associated with attachment insecurities (abandonment anxiety, avoidance of intimacy) and emotional regulation and whether these three variables are associated with romantic breakup adjustment in youth (i.e., distress, resilience, psychiatric symptoms); and 2) childhood maltreatment is associated with attachment insecurities, which would be linked to emotional regulation, ultimately explaining romantic breakup adjustment in youth. Method: We assessed history of childhood maltreatment, attachment, emotional regulation and romantic breakup adjustment in a sample of 303 university students who experienced an unwanted breakup in the last five months. Path analyses were mesured. Results: 1) Distress was directly associated with abandonment anxiety (p < ,01), dysregulation (p < ,05), and emotional regulation (p < ,01). Psychological symptoms were directly associated with childhood maltreatment (p < ,01), abandonment anxiety (p < ,01), dysregulation (p < ,01), and emotional regulation (p < ,05). Resilience was directly associated with childhood maltreatment, avoidance of intimacy, emotional regulation (p < ,01) as well as dysregulation (p < ,05). 2) Childhood maltreatment was indirectly associated with distress (p < ,01), resilience (p < ,01), and psychological symptoms (p < ,01) after breakup through attachment anxiety and avoidance, and emotional regulation and dysregulation. Conclusion: Youth with a history of childhood maltreatment who recently experienced a romantic breakup may benefit from interventions aimed at working on attachment insecurities and improving emotional regulation skills.

Les expériences de maltraitance vécues à l’enfance ont été associées à une morbidité physique et psychologique, dont un plus grand risque de développer des maladies cardiovasculaires (MCV). Ceci pourrait être expliqué par les effets de la maltraitance sur la régulation émotionnelle et l’indice de masse corporelle (IMC). Objectifs : Évaluer si (1) la maltraitance est associée à un IMC plus élevé au départ et à une augmentation plus importante de l'IMC 5 ans plus tard chez les adultes plus âgés souffrants de maladie coronarienne (MAC) ou d'autres maladies chroniques; (2) le sexe et/ou le statut coronarien influencent ces résultats; et (3) les symptômes d'anxiété, de dépression et de stress perçu (comme indices de dérégulation émotionnelle) expliquent l'association entre la maltraitance et l’IMC au suivi. Participants et méthodes : 1232 hommes et femmes (âgés de 60,86 ± 6,95 ans) ont rempli des questionnaires validés sur la maltraitance et les symptômes de détresse psychologique. Le poids en kilogrammes et la taille du participant ont été recueillis. L'IMC du participant a été calculé en utilisant le rapport poids (kg)/taille (m2). Résultats : La maltraitance n'était pas associée à l'IMC au départ ni lors du suivi. Cette relation n'était pas modérée par le sexe ou le statut de MAC. La maltraitance dans l'enfance était associée à une détresse psychologique significativement plus importante au départ (tous les p < ,001), mais ces derniers n'expliquaient pas cette relation au suivi. Conclusion : La maltraitance n'était pas associée à l'IMC au départ ni à l'IMC cinq ans plus tard. La dysrégulation émotionnelle résultant de la détresse psychologique a été associée à un risque accru de morbidité et de mortalité et peut représenter une cible importante pour la prévention et l'intervention, y compris en ce qui concerne la promotion d'habitudes de vie plus saines chez des personnes ayant vécu de la maltraitance. / Objectives: Childhood trauma has been associated with greater psychological and physical morbidity, including a greater risk of developing coronary artery disease (CAD). Mechanisms leading to increased risk of illness may involve emotional dysregulation and increased body mass index (BMI). This study evaluated whether (1) childhood maltreatment is associated with higher BMI at baseline and with greater increases in BMI 5 years later among older adults with CAD or other chronic illnesses; (2) sex and/or CAD status influence these results; and (3) symptoms of anxiety, depression, and perceived stress (as indicators of emotional dysregulation) mediate the association between childhood maltreatment and BMI at 5-year follow-up. Participants and Methods: A total of 1232 men and women (aged 60.86 [6.95] years) completed validated questionnaires on childhood maltreatment and symptoms of psychological distress. Weight in kilograms and height were collected for each participant, and their BMI was calculated using the ratio of weight (kg)/height (m2).Findings: Childhood maltreatment was not associated with BMI at baseline nor at follow-up. This relation was not moderated by sex nor CAD status. Childhood maltreatment was associated with significantly greater psychological distress at baseline (all ps<.001), though the latter was not found to mediate this relation at follow-up. Conclusion: Childhood maltreatment was not associated with BMI at baseline nor with BMI five years later. Emotional dysregulation resulting from psychological distress has been associated with increased risk for morbidity and mortality and may represent an important target for prevention and intervention, including as concerns promoting healthier lifestyle habits. However, further studies are needed.

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Obsessive-compulsive disorder (OCD) is heterogeneous. Clinical presentation of OCD differs by sex and age-of-onset and evidence supports classification based on these subtypes. The prevalence of OCD in the general population is 2%. However, it has been established that women tend to experience onset and exacerbation of OCD during reproductive milestones. In particular, the prevalence of postpartum OCD is between 4 to 9%. This study seeks to examine the effects of past childhood maltreatment and S/Lg-allele status of the 5-HTTLPR polymorphism on perinatal obsessive-compulsive symptoms and aberrant resting state functional connectivity in the postpartum period. Forty women participated in the first visit and sixteen women have been followed up with in the postpartum period. 5-HTTLPR genotype was determined from whole blood samples via polymerase chain reaction and a restriction fragment length digest. We used the Yale-Brown Obsessive-Compulsive Scale and Perinatal Obsessive-Compulsive scale to measure symptom severity. Resting state functional connectivity was determined from functional magnetic resonance imaging data. Obsessive-compulsive symptoms during late pregnancy are significantly predicted by 5-HTTLPR genotype, past history of total childhood maltreatment or childhood emotional neglect and trait anxiety symptoms. Whereas obsessive-compulsive symptoms during the postpartum period are predicted by poor sleep quality and childhood emotional maltreatment or 5-HTTLPR genotype, childhood emotional maltreatment and trait anxiety symptoms. Seed to region-of-interest analysis was employed to evaluate resting state functional connectivity differences between OCD patients and healthy controls in the postpartum period. Compared to healthy controls, OCD patients show greater connectivity between the caudate nucleus with the orbitofrontal cortex, the pars triangularis and the cingulate area. The insular cortex shows decreased connectivity between the right and left, the dorsal anterior cingulate area and the pars opercularis. The amygdala has increased connectivity with the cingulate area, the calcarine fissure, the supramarginal gyrus and decreased connectivity with the gyrus rectus. The above clinical and neuroimaging findings are in line with past work. However, this is the first study to show both 5-HTTLPR genotype and history of childhood maltreatment predict obsessive-compulsive symptoms in a perinatal population. Further, the resting state data replicates findings in the OCD literature but the study is the first to show this in postpartum women. This study serves as a platform for future work to further investigate both gene-environment interactions and distinct neuroimaging correlates in perinatal OCD. / Thesis / Master of Science (MSc)

Introdução: O transtorno bipolar (TB) é um problema crônico, de evolução cíclica, altamente prevalente na população geral e está associado a importante incapacitação dos pacientes e a déficits cognitivos e funcionais, constituindo, assim, um importante problema de saúde pública. A etiologia do TB parece ser multifatorial, resultante da interação entre fatores genéticos e ambientais; estudos apontam que a predisposição para manifestação de episódios pode advir da exposição a maus-tratos na infância (MTI), que comprometem o desenvolvimento emocional, cerebral e cognitivo das crianças e estão presentes em 30% a 60% dos portadores de TB. No TB, os MTI vem sendo associados com idade de início mais precoce, pior evolução clínica, maior incidência de comorbidades, apesar da literatura ser escassa e não conclusiva, tem sido associado também a alterações do funcionamento cognitivo e da morfologia cerebral. Objetivo: Investigar se o perfil cognitivo e a morfometria cerebral de portadores de TBI eutímicos diferencia-se com a exposição ou não a maus-tratos sofridos na infância. Método: 75 portadores de TBI eutímicos, com idades entre 18 e 45 anos, atendidos no ambulatório do Programa de Transtornos Afetivos (GRUDA) IPq-HC-FMUSP, sendo 32 sem história de MTI e 43 com história de MTI, de acordo com o ponto de corte do Childhood Trauma Questionnaire (CTQ) e 46 voluntários sadios do ponto de vista físico e mental, com idades entre 18 e 45 anos, sem história de MTI de acordo com o CTQ e sem parentes de primeiro grau com transtornos psiquiátricos foram submetidos a uma bateria de testes neuropsicológicos que avaliou as funções atencionais, mnêmicas, executivas e cognição social e a um estudo de imagem por ressonância magnética. Resultados: Os resultados apontaram para uma diferença de desempenho cognitivo entre os grupos em uma das medidas de flexibilidade mental (p=0,04), em uma de raciocínio matricial (p=0,035) e na capacidade de reconhecimento de emoções faciais de tristeza (REF, p=0,022). Em relação à morfometria cerebral, pôde-se observar que o volume do Núcleo Caudado apresentou diferença estatisticamente significativa entre os três grupos, tanto no hemisfério direito (p=0,002) como no esquerdo (0,008). No hemisfério esquerdo, a área do Órbito Frontal Medial (p=0,0466), a área do Pré-cuneo (p=0,0193) e a área do Parietal Superior (p=0,0063) apresentaram diferenças estatisticamente significativas. No hemisfério direito, a área do Órbito Frontal Medial (p=0,0200), a área do Pré-cuneo (p=0,0337), a área do Parietal Superior (p=0,0007), a espessura da Parte Triangular do Córtex Frontal (p=0,0013), a espessura do Pré-central (p=0,0307) e a espessura do Frontal Superior (p=0,0425) apresentaram diferenças estatisticamente significativas. Por fim, a partir de uma análise exploratória, pôde-se observar que no grupo de portadores de TB com MTI os resultados apontam para possíveis associações entre regiões cerebrais e desempenhos cognitivos, sendo elas: volume do Hipocampo Direito e o TMT-B (pinteração= 0,002, r = -0,40, pr=0,013), área do Giro Superior Frontal Direito e o SCWT-I (pinteração= 0,0008, r = -0,36, pr=0,0185), área do Órbito Frontal Medial Esquerdo e o FCR-cópia (pinteração= 0,004, r = 0,49, pr=0,014), espessura do Órbito Frontal Medial Direito e COWAT-total (pinteração= 0,004, r = 0,46, pr=0,003), espessura do Frontal Medial Rostral Esquerdo e WCST-erros (pinteração= 0,007, r = -0,42, pr=0,007). Conclusões: Apesar da limitação do tamanho amostral e do número de comparações estatísticas realizadas, este é o primeiro estudo a avaliar a associação entre MTI, funcionamento cognitivo e morfometria cerebral. Os resultados foram sugestivos de que a magnitude das correlações entre as características morfométricas e cognitivas podem ser moduladas pela exposição a MTI e pelo status de caso (portador de TB) / Introduction: Bipolar disorder (BD) is a chronic, cyclically-evolving problem that is highly prevalent in the general population and is associated with significant disability of the patients and cognitive and functional deficits, thus constituting an important public health problem. The etiology of BD seems to be multifactorial, resulting from the interaction between genetic and environmental factors, and studies show that the predisposition to the manifestation of episodes of BD may result from exposure to childhood maltreatment (CM), which compromises the emotional, cerebral and cognitive development and seems to be present in between 30 and 60% of BD patients. In BD, CM have been associated with earlier onset age, worse clinical course, higher incidence of comorbidities and, although the literature is scarce and not conclusive, it has also been associated with changes in cognitive function and brain morphology. Objective: To investigate whether the cognitive profile and the brain morphometry of patients with euthymic BD differ between those exposed or non-exposed to CM. Method: 75 euthymic BD patients, aged between 18 and 45 years, attended at the ambulatory of the Affective Disorders Program (GRUDA) IPq-HC-FMUSP, 32 of which had no history of CM and 43 with a positive history of CM according to the cut-off of the Childhood Trauma Questionnaire (CTQ) and 46 physically and mentally healthy volunteers, aged 18-45 years, with no history of CM according to the CTQ and no first-degree relatives with psychiatric disorders were submitted to a battery of neuropsychological tests that evaluated attentional, mnemonic, executive, and social cognition functions and a study of magnetic resonance imaging. Results: The results point to a difference in cognitive performance between groups in one of the measures of mental flexibility (p = 0.04), in one of matrix reasoning (p = 0.035) and in the ability to recognize facial emotions of sadness FER, p = 0.022). Regarding cerebral morphometry, it can be observed that the volume of the Caudate Nucleus showed a statistically significant difference between the three groups, both in the right hemisphere (p = 0.002) and in the left hemisphere (0.008). In the left hemisphere, the area of Medial Orbital Frontal (p = 0.0466), the area of Precuneus (p = 0.0193) and the area of Superior Parietal (p = 0.0063) presented statistically significant differences. In the right temisphere, the area of Medial Orbital Frontal (p = 0.0200), the area of Precuneus (p = 0.0337), the area of Superior Parietal (p = 0.0007), the thickness of Pars Triangularis (p = 0.0013), the thickness of Precentral (p = 0.0307) and the thickness of Superior Frontal (p = 0.0425) presented statistically significant differences. Finally, from this exploratory analysis, it is possible to observe that in the group of BD with CM the results point to possible associations between brain regions and cognitive performance, specifically: Right Hippocampus Volume and TMT-B (pinteraction = 0,002, r = -0,40, pr=0,013), Right Superior Frontal Area and SCWT-I (pinteraction = 0.0008, r = -0.36, pr = 0.0185), Left Medial Orbital Frontal area and FCR-copy (pinteraction= 0,004, r = 0,49, pr=0,014), Right Medial Orbital Frontal Thickness and COWAT-total (pinteraction = 0.004, r = 0.46, pr= 0.003), Left Rostral Medial Frontal Thickness and WCST-errors (pinteraction = 0.007, r = -0.42, pr = 0.007). Conclusions: Despite the limitation of the sample size and the number of statistical comparisons performed, this is the first study to evaluate the association between CM, cognitive functioning and brain morphometry. The results are suggestive of the magnitude of the correlations between the characteristics morphometric and cognitive variables can be modulated by exposure to CM and by case status (BD patients)