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Suicidal behavior is result of the interaction of several contributors, including genetic and environmental factors. The integration of approaches considering the polygenic component of suicidal behavior, such as polygenic risk scores (PRS) and DNA methylation is promising for improving our understanding of the complex interplay between genetic and environmental factors in this behavior. The aim of this study was the evaluation of DNA methylation differences between individuals with high and low genetic burden for suicidality. The present study was divided into two phases. In the first phase, genotyping with the Psycharray chip was performed in a discovery sample of 568 Mexican individuals, of which 149 had suicidal behavior (64 individuals with suicidal ideation, 50 with suicide attempt and 35 with completed suicide). Then, a PRS analysis based on summary statistics from the Psychiatric Genomic Consortium was performed in the discovery sample. In a second phase, we evaluated DNA methylation differences between individuals with high and low genetic burden for suicidality in a sub-sample of the discovery sample (target sample) of 94 subjects. We identified 153 differentially methylated sites between individuals with low and high-PRS. Among genes mapped to differentially methylated sites, we found genes involved in neurodevelopment (CHD7, RFX4, KCNA1, PLCB1, PITX1, NUMBL) and ATP binding (KIF7, NUBP2, KIF6, ATP8B1, ATP11A, CLCN7, MYLK, MAP2K5). Our results suggest that genetic variants might increase the predisposition to epigenetic variations in genes involved in neurodevelopment. This study highlights the possible implication of polygenic burden in the alteration of epigenetic changes in suicidal behavior.

Introducción: Un trastorno mental es un síndrome caracterizado por una alteración del estado cognitivo, la regulación o el desarrollo del individuo. Este grupo de pacientes puede requerir un cuidador primario informal (CPI en lo sucesivo) que lo asista en sus necesidades físicas, emocionales, sociales, de atención médica o cohesión familiar. En este contexto, la Entrevista de Carga de Zarit (ECZ ) es un instrumento utilizado en la evaluación de dichos CPI. Objetivo: Validar la ECZ en una muestra de CPI de pacientes con diagnostico psiquiátrico. Método: Se empleó un diseño transversal, con un muestreo no probabilístico. Participaron 235 CPI, quienes contestaron concurrentemente la ECZ y el cuestionario SF-36. Resultados y Discusión: La versión obtenida en el presente estudio mostró un instrumento de 17 ítems con una consistencia interna satisfactoria de la escala global. Se obtuvieron tres subescalas: Impacto del cuidador, Relaciones interpersonales y Expectativas de autoeficacia, así como un indicador cognitivo. La validez concurrente mostró resultados significativos. El análisis psicométrico realizado indica que la ECZ en CPI de pacientes con diagnóstico psiquiátrico tiene una buena consistencia interna, mayor que la de la versión original. Comparada con las demás validaciones del Zarit, mostró una estructura factorial similar. La relevancia de los resultados obtenidos radica en su utilidad clínica y de investigación en grupos de cuidadores que pueden requerir atención psicosocial.

Background Suicidal behavior may be divided into completed suicide, suicide attempts, and suicidal ideation. It has been suggested that these behaviors represent a continuum and result from the interaction of several contributors, including genetic and environmental factors. The integration of approaches considering the polygenic component of suicidal behavior, such as polygenic risk scores (PRS) and DNA methylation is promising for improving our understanding of the complex interplay between genetic and environmental factors in this behavior. The aim of this study was the evaluation of DNA methylation differences between individuals with high and low genetic burden for suicidality. Methods The present study was divided into two phases. In the first phase, genotyping with the Psycharray chip was performed in a discovery sample of 568 Mexican individuals, of which 149 had suicidal behavior (64 individuals with suicidal ideation, 50 with suicide attempt and 35 with completed suicide) and 419 non-suicide controls. Then, a PRS analysis based on summary statistics from the Psychiatric Genomic Consortium was performed in the discovery sample. In a second phase, we evaluated DNA methylation differences between individuals with high and low genetic burden for suicidality in a sub-sample of the discovery sample (target sample) of 94 subjects. Methylation profile from individuals in the target sample was assessed with the Illumina Infinium Human Methylation EPIC BeadChip. Results We identified 153 differentially methylated sites between individuals with low and high-PRS. From these, 91 sites were hypermethylated and 62 hypomethylated in the high PRS group relative to low PRS group. Among genes mapped to differentially methylated sites, we found genes involved in neurodevelopment and ATP binding. Discussion To our knowledge, this is the first study integrating polygenic risk scores and DNA methylation in suicidality. Our results suggest that genetic variants might increase the predisposition to epigenetic variations in genes involved in neurodevelopment. This study highlights the possible implication of polygenic burden in the alteration of epigenetic changes in suicidal behavior.