RESUMEN
Several studies have examined the association of externalizing polygenic scores (PGS) with externalizing symptoms in samples of European ancestry. However, less is known about the associations of externalizing polygenic vulnerability in relation to phenotypic externalizing disorders among individuals of different ancestries, such as Mexican youth. Here, we leveraged the largest genome-wide association study on externalizing behaviors that included over 1 million individuals of European ancestry to examine associations of externalizing PGS with a range of externalizing disorders in Mexican adolescents, and investigated whether adversity exposure in childhood moderated these associations. Participants (N = 1064; age range 12-17 years old; 58.8% female) were adolescents recruited for a general population survey on adolescent mental health in the Mexico City Metropolitan region and were genotyped. Childhood adversity exposure and externalizing disorders, specifically attention-deficit hyperactivity disorder (ADHD), conduct disorder, oppositional defiant disorder, and substance use disorder, were assessed via the computer-assisted World Mental Health Composite International Diagnostic Interview for adolescents. A greater externalizing PGS was associated with a greater odds of any externalizing disorder (OR = 1.29 [1.12, 1.48]; p < 0.01) and ADHD (OR = 1.40 [1.15, 1.70]; p < 0.01) in the whole sample, and in females in particular. There were no main effects of the externalizing PGS on conduct disorder, oppositional defiant disorder, or substance use disorder, nor did adversity exposure moderate these associations. Our results suggest that greater genetic propensity for externalizing disorders is associated with increased odds of any externalizing disorders and ADHD among Mexican adolescents, furthering our understanding of externalizing disorder manifestation in this population.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad , Trastorno de la Conducta , Trastornos Relacionados con Sustancias , Humanos , Adolescente , Femenino , Niño , Masculino , Estudio de Asociación del Genoma Completo , México , Trastorno de la Conducta/epidemiología , Trastorno de la Conducta/genética , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Trastorno por Déficit de Atención con Hiperactividad/genética , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Trastornos Relacionados con Sustancias/epidemiología , Trastornos Relacionados con Sustancias/genética , Trastornos Relacionados con Sustancias/complicacionesRESUMEN
Suicide is a major public health problem in Mexico and around the world. Genetic predisposition for major depressive disorder (MDD) has been associated with increased risk for suicidal behaviors (SB) in populations of European ancestry (EA). Here, we examine whether MDD polygenic risk scores (MDD PRS), derived from a genome-wide association study involving EA individuals, predict SB, including ideation, planning, and attempt, among Mexican youth using a longitudinal design. At baseline, participants (N = 1,128, 12-17 years, 55% women) were interviewed and genotyped as part of a general population survey on adolescent mental health. Eight years later, they were recontacted for a follow up visit (N = 437, 20-25 years, 63% women). At both assessments, individuals reported on their engagement in SB within the past year. MDD PRS were significantly positively associated with SB, particularly suicide ideation and planning during adolescence, accounting for ~4-5% of the variance in these outcomes. In contrast, associations between MDD PRS and SB during young adulthood did not reach statistical significance. Our results suggest that increased genetic liability for depression increased risk for SB, particularly during adolescence, expanding our knowledge of the genetic underpinnings of SB.
Asunto(s)
Trastorno Depresivo Mayor , Ideación Suicida , Adolescente , Adulto , Depresión/genética , Trastorno Depresivo Mayor/genética , Femenino , Estudio de Asociación del Genoma Completo , Humanos , Masculino , México , Factores de Riesgo , Adulto JovenRESUMEN
The BDNF is required for the development and proper function of the central nervous system, where it is involved in a variety of neural and molecular events relevant to cognition, learning, and memory processes. Although only a functional mature protein is synthesized, the human BDNF gene possesses an extensive structural complexity, including the presence of multiple promoters, splicing events, and 3´UTR poly-adenylation sites, resulting in an intricate transcriptional regulation and numerous messengers RNA. Recent data support specific cellular roles of these transcripts. Moreover, a central role of epigenetic modifications on the regulation of BDNF gene transcription is also emerging. The present essay aims to summarize the published information on the matter, emphasizing their possible implications in health and disease or in the treatment of different neurologic and psychiatric disorders.