Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders

Transtorno de oposição e desafio e transtorno de conduta: os desfechos no TDAH em adultos Oppositional defiant disorder and conduct disorder: their outcomes into adulthood

Os autores examinam a influência dos transtornos de oposição e desafio (TOD), de conduta (TC) e de personalidade anti-social (TPAS) ao longo da vida do indivíduo com TDAH. Os principais achados mostram que o TDAH é modulado por essas comorbidades e que seu prognóstico é modificado dependendo da presença ou não desses transtornos. O transtorno de oposição e desafio intensificaria as características de impulsividade e isolacionismo do TDAH, porém não acarretaria em um aumento na incidência de TPAS na vida adulta. Já o TC associado ao TDAH implica um aumento significativo na impulsividade e agressividade, estando associado significativamente a TPAS e um pior prognóstico. A diferenciação entre os diferentes transtornos e seu correto diagnóstico é essencial para o tratamento adequado do TDAH. Futuros estudos precisam determinar se o tratamento do TDAH produziria uma mudança significativa no prognóstico desse grupo de pacientes.<br>The authors examine the influence of oppositional defiant disorder (ODD), conduct disorder (CD) and anti-social personality disorder (ASPD) on attention deficit/hyperactivity disorder (ADHD) across life span. The findings showed that ADHD is modulated by this comorbidities and ADHD prognosis is modified depending on the presence or the absence of those disorders. ODD intensifies ADHD impulsivity and isolationism, but does not lead to an increase in the prevalence of ASPD in adulthood. Otherwise, CD associated with ADHD increases significantly the levels of impulsivity and aggressiveness, is associated with ASPD and a poor outcome. The appropriate approach to ADHD must be based on the correct diagnosis of different comorbidities to predict the outcomes. Further studies are needed to investigate if the treatment of ADHD can produce a significant improvement on the outcomes of this group of patients

FEATURE REVIEW

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Painel brasileiro de especialistas sobre diagnóstico do transtorno de déficit de atenção/hiperatividade (TDAH) em adultos Panel brasileño de especialistas sobre diagnóstico del trastorno de d��ficit de atención/hiperactividad (TDAH) en adultos Brazilian consensus of specialists on the diagnosis of attention-deficit/hyperactivity disorder in adults

Considerando-se as dificuldades atuais do diagnóstico do transtorno do déficit de atenção/hiperatividade em adultos, foram reunidos especialistas brasileiros que fazem pesquisas nesta área, de modo a produzir diretrizes de consenso para uso no país. Foi realizada uma revisão não-sistemática preliminar e concebido um texto inicial, que foi repetidamente avaliado e editado pelos autores, com acréscimos e correções ao longo de 6 meses, através de correio eletrônico e de uma reunião posterior, patrocinada pela Associação Brasileira do Déficit de Atenção. A versão preliminar foi apresentada publicamente durante o congresso anual da Associação Brasileira de Psiquiatria, com comentários e sugestões dos participantes, para a redação da versão final.<br>Considerándose las dificultades actuales del diagnóstico del trastorno del déficit de atención/hiperactividad en adultos, se reunieron especialistas brasileños que investigan en esa área, de modo a producir directrices de consenso para uso en el país. Se realizó una revisión no-sistemática preliminar y se concibió un texto inicial, que ha sido repetidamente evaluado y editado por los autores, con acrecimos y correcciones a lo largo de 6 meses, a través de correo electrónico y de una reunión posterior, patrocinada por la Asociación Brasileña del Déficit de Atención. La versión preliminar ha sido presentada públicamente durante el congreso anual de la Asociación Brasileña de Psiquiatría, con comentarios y sugerencias de los participantes para la redacción de la versión final.<br>Present difficulties in the diagnosis of attention-deficit/hyperactivity disorder in adults have prompted Brazilian specialists involved in research in this area to make a consensus to be used in the country. A non-systematic preliminary review was repeatedly evaluated by all authors, who added new material, commented and corrected parts of the text for 6 months through electronic mail and a further meeting sponsored by the Brazilian Association of Attention-Deficit Disorder. The preliminary version was publicly presented during the annual congress of the Associação Brasileira de Psiquiatria (Brazilian Association for Psychiatry) for appraisal and suggestions from participants in order to prepare the final version