TY - JOUR PY - 2023// TI - Mediating effect of genome-wide DNA methylation on suicidal ideation induced by stressful events JO - Psychiatric genetics A1 - De Luca, Vincenzo A1 - Al-Chalabi, Nzaar A1 - Chaudhary, Zanib A1 - Qian, Jessica A1 - Borlido, Carol A1 - Chintoh, Araba A1 - Gerretsen, Philip A1 - Graff, Ariel A1 - Remington, Gary A1 - Sanches, Marcos A1 - Battaglia, Marco SP - 26 EP - 33 VL - 33 IS - 1 N2 - 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.

Language: en

LA - en SN - 0955-8829 UR - http://dx.doi.org/10.1097/YPG.0000000000000331 ID - ref1 ER -