Mediating effect of genome-wide DNA methylation on suicidal ideation induced by stressful events

Abstract

Objective Schizophrenia is a debilitating disease that is associated with higher rates of death by unnatural causes including suicide. Exposure to stressful events is an important risk factor for suicidal ideation (SI); however, the mechanisms that link stress, SI, and suicide remain unclear. Epigenetic processes are involved in both vulnerability to suicidal behavior and stress. Therefore, we sought to study the relationship between epigenetic modifications and suicidal behavior and stress. Methods This pilot study was conducted on 39 patients diagnosed with schizophrenia (54% men and age 45.5 ± 12.7). We analyzed the effects of (a) stress exposure and (b) the mediation of DNA methylation [via an epigenetic wide association study (EWAS) of more than 450 000 CpG sites across the genome] on SI severity. Results The top CpG site mediating the effect of global stress exposure on SI was cg27660192 located in an intergenic region on chromosome 11, exerting a facilitating effect on worsening SI through DNA hypomethylation. Conclusion These preliminary results indicate that DNA methylation in peripheral tissues can shed light on the complex relationship between stress and SI in schizophrenia.