The interaction of P11 methylation and early-life stress impacts the antidepressant response in patients with major depressive disorder.

PURPOSE:The present research investigates the influence of P11 gene DNA methylation combined with life stress on the response to antidepressants in the first two weeks. METHODS:A total of 291 Han Chinese patients with major depressive disorder and 100 healthy controls were included. The Life Events Scale and the Childhood Trauma Questionnaire were used to assess stress. The primary endpoint was the Hamilton Depression Rating Scale-17 reduction rate after two weeks of treatment. The Illumina HiSeq Platform was used to detect the methylation of 74 CpG sites of the P11 gene in peripheral blood samples. RESULTS:The mean methylation of all P11 CpG sites, as well as the methylation at 4 CpG sites (P11-2-169, P11-2-192, P11-2-202, P11-2-204), were significantly higher in patients with MDD than in healthy controls (FDR-corrected P < 0.05). The response to antidepressants was associated with the following interactions: the CTQ score and P11-3-185 site methylation (OR = 0.297, FDR-corrected P = 0.023), the CTQ physical neglect score and P11-2-117 site methylation (OR = 0.005, FDR-corrected P = 0.033), and the CTQ emotional abuse score and P11-3-185 site methylation (OR = 0.001, FDR-corrected P = 0.023). CONCLUSIONS:The methylation of the P11 gene was significantly higher in patients with major depressive disorder. The interaction of P11 DNA methylation and early-life stress may influence the short-term antidepressant treatment response.