Transtorno obsessivo compulsivo (TOC): metanálise de estudos genético-epidemiológicos e análise das associações entre características clínicas maternas e de seus filhos e entre substância branca de crianças e psicopatologia
Data
2022-06-10
Autores
Blanco-Vieira, Thiago [UNIFESP]
Orientadores
Rosário, Maria Conceição [UNIFESP]
Tipo
Tese de doutorado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
INTRODUÇÃO: O transtorno obsessivo compulsivo (TOC) é um transtorno heterogêneo, causado por uma complexa interação de fatores genéticos, neurobiológicos e ambientais. O objeto de estudo dessa tese é a compreensão dessa doença sob uma perspectiva neurodesenvolvimental, partindo do contexto familial até seus correlatos no desenvolvimento, investigando desde características clínicas e genético familiares até achados de neuroimagem relacionadas a esta doença. Os achados são apresentados no formato de três estudos/publicações científicas. OBJETIVOS: Estudo 1 – realizar revisão sistemática e meta análise dos estudos de famílias e com gêmeos de pacientes com TOC para estimar o risco familiar e herdabilidade do TOC; Estudo 2 – investigar a presença de dimensões de sintomas obsessivo compulsivos (SOC) em mães de crianças em idade escolar e o impacto desses SOC na presença de SOC e/ou outros transtornos em seus filhos; Estudo 3 – investigar alterações na microestutura da substância branca de crianças em idade escolar e sua associação com a presença de SOC ou outros problemas emocionais e do comportamento ao longo da transição da infância para a adolescência. MÉTODOS: O estudo 1 corresponde a revisão sistemática com metanálise dos estudos de família e estudos de gêmeos publicados até Junho/2021. O estudo 2 é um estudo transversal, envolvendo 2511 duplas de mães e filhos. O estudo comparou variáveis sociodemográfica e clinicas das mães, incluindo a presença de SOC aferidos pela versão abreviada da Dimensional Yale-Brown Obsessive Compulsive Scale (DYBOCS-SV) e a presença de sintomas psiquiátricos pela MINI, com a presença de SOC e características psicopatológicas de seus filhos. O estudo 3 tem desenho longitudinal, com amostra inicial de 256 sujeitos submetidos à coleta de neuroimagem para processamento dos dados de DTI para cálculo dos valores de anisotropia fracionada (FA) e difusidade média (MD) para a radiação talâmica, giro do cíngulo, hipocampo e fascículo uncinado, bilateralmente. Esses valores foram correlacionados com a presença de SOC e/ou outros sintomas psicopatológicos aferidos pela Child Behavior Checklist respondida em três momentos durante a transição da infância para adolescência. RESULTADOS: Estudo 1 – O TOC é fortemente familial, com destaque para o TOC de inicio precoce. Os achados de gêmeos confirmaram uma herdabilidade genética de 52%; Estudo 2 – A prevalência de SOC nas mães foi de cerca de 40%. Houve correlação positiva estatisticamente significativa entre SOC maternos e sintomas internalizantes e externalizantes em seus filhos. A presença de SOC nas crianças esteve associada com psicopatologia geral materna. Estudo 3 – Nenhum dos tratos pesquisados mostrou correlação entre as medidas de FA e sintomas psicopatológicos das crianças. No entanto, houve correlação entre os valores de MD na radiação talâmica em crianças que desenvolveram SOC e problemas comportamentais e emocionais à avaliação inicial e no inicio da adolescência. CONCLUSÕES: Estudo 1 – O estudo compreende uma relevante atualização do conhecimento em epidemiologia genética do TOC e reforça a agregação familiar dessa doença. Estudo 2 – A presença e gravidade de SOC maternos estão relacionadas com manifestação de problemas emocionais e comportamentais em seus filhos. Estudo 3 – Alterações da difusidade média no hemisfério direito nas regiões de projeção talâmica, giro de cíngulo e fascículo uncinado estão associadas com o desenvolvimento de SOC e sintomas psicopatológicos em geral em crianças em idade escolar.
INTRODUCTION: The obsessive-compulsive disorder (OCD) is a heterogeneous condition caused by a complex interaction between genetic, neurobiological and environmental factors. The main purpose of this thesis is to provide a comprehensive overview of this disorder from a neurodevelopmental perspective, emerging from the familial context to its individual developmental correlates, assessing clinical, genetic epidemiology and neuroimage findings associated to this condition. The findings are presented along 3 scientific papers. OBJECTIVES: Study 1 – to perform a systematic review and metanalysis of OCD family and twin studies in order to estimate the family risk and herdability of OCD; Study 2 – to assess the prevalence of obsessive compulsive symptom (OCS) dimensions in mothers of school-age children and the association between maternal OCS and their children’s psychopatological status; Study 3 – to assess the presence of white matter microstructure alterations and its association with the presence of OCS and/or other emotional and behavioral problems across the transition from childhood to adolescence. METHODS: The Study 1 provides a systematic review and metanalysis of the family and twin studies published until June/2021. The Study 2 is a cross-sectional study enrolling a total sample of 2511 mother-child pairs. The study compared the sociodemographic and clinical variables of the mothers, including the presence of OCS assessed by the Dimensional Yale-Brown Obsessive Compulsive Scale (DYBOCS-SV) and the presence of psychiatric symptoms assessed by the MINI, with the presence of OCS and other psychopatological symptoms of their children. The Study 3 is a longitudinal design study reporting data from a initial sample of 256 subjects assessed by DTI neuroimage procedures in order to assess the fractional anisotropy (FA) and mean diffusity (MD) values of the thalamic radiation, cingulum gyrus, hippocampus and uncinate fasciculus, bilaterally. The correlations between the OCS and emotional and behavioral symptoms according to the Child Behavior Checklist were calculated in three different time-points during the transition from the childhood to the adolescence. RESULTS: Study 1 – OCD is strongly familial, especially the early-onset OCD subtype. The pooled data from twin studies confirmed a genetic herdability around 52%. Study 2 – The prevalence of OCS in the mothers was 40%. There was a positive significant correlation between maternal OCS and internalizing and externalizing symptoms in their children. The presence of OCS in the children was associated to maternal psychiatric symptoms. Study 3 – There were no correlations between the FA measures of the investigated tracts and psychopatological symptoms. However, there were correlations between the MD values in the thalamic radiation in children with OCS and behavioral and emotional problems in baseline and early adolescence. CONCLUSIONS: Study 1 – The study represents a revelant update of the genetic epidemiology knowledge of OCD and reinforce the high family aggregation rates of the disorder. Study 2 – The presence and severity of maternal OCS are associated to emotional and behavioral problems in their children. Study 3 – Altered mean diffusity on the right thalamic projections, cingulum and uncinate fasciculus are associated with the presence of OCS and general psychopatology in school-age children.
INTRODUCTION: The obsessive-compulsive disorder (OCD) is a heterogeneous condition caused by a complex interaction between genetic, neurobiological and environmental factors. The main purpose of this thesis is to provide a comprehensive overview of this disorder from a neurodevelopmental perspective, emerging from the familial context to its individual developmental correlates, assessing clinical, genetic epidemiology and neuroimage findings associated to this condition. The findings are presented along 3 scientific papers. OBJECTIVES: Study 1 – to perform a systematic review and metanalysis of OCD family and twin studies in order to estimate the family risk and herdability of OCD; Study 2 – to assess the prevalence of obsessive compulsive symptom (OCS) dimensions in mothers of school-age children and the association between maternal OCS and their children’s psychopatological status; Study 3 – to assess the presence of white matter microstructure alterations and its association with the presence of OCS and/or other emotional and behavioral problems across the transition from childhood to adolescence. METHODS: The Study 1 provides a systematic review and metanalysis of the family and twin studies published until June/2021. The Study 2 is a cross-sectional study enrolling a total sample of 2511 mother-child pairs. The study compared the sociodemographic and clinical variables of the mothers, including the presence of OCS assessed by the Dimensional Yale-Brown Obsessive Compulsive Scale (DYBOCS-SV) and the presence of psychiatric symptoms assessed by the MINI, with the presence of OCS and other psychopatological symptoms of their children. The Study 3 is a longitudinal design study reporting data from a initial sample of 256 subjects assessed by DTI neuroimage procedures in order to assess the fractional anisotropy (FA) and mean diffusity (MD) values of the thalamic radiation, cingulum gyrus, hippocampus and uncinate fasciculus, bilaterally. The correlations between the OCS and emotional and behavioral symptoms according to the Child Behavior Checklist were calculated in three different time-points during the transition from the childhood to the adolescence. RESULTS: Study 1 – OCD is strongly familial, especially the early-onset OCD subtype. The pooled data from twin studies confirmed a genetic herdability around 52%. Study 2 – The prevalence of OCS in the mothers was 40%. There was a positive significant correlation between maternal OCS and internalizing and externalizing symptoms in their children. The presence of OCS in the children was associated to maternal psychiatric symptoms. Study 3 – There were no correlations between the FA measures of the investigated tracts and psychopatological symptoms. However, there were correlations between the MD values in the thalamic radiation in children with OCS and behavioral and emotional problems in baseline and early adolescence. CONCLUSIONS: Study 1 – The study represents a revelant update of the genetic epidemiology knowledge of OCD and reinforce the high family aggregation rates of the disorder. Study 2 – The presence and severity of maternal OCS are associated to emotional and behavioral problems in their children. Study 3 – Altered mean diffusity on the right thalamic projections, cingulum and uncinate fasciculus are associated with the presence of OCS and general psychopatology in school-age children.
Descrição
Citação
BLANCO-VIEIRA, T. Transtorno obsessivo compulsivo (TOC): metanálise de estudos genético-epidemiológicos e análise das associações entre características clínicas maternas e de seus filhos e entre substância branca de crianças e psicopatologia. São Paulo, 2022. 142 f. Tese (Doutorado em Psiquiatria e Psicologia Médica) – Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (UNIFESP), São Paulo, 2022.