The impact of HTR1A and HTR1B methylation combined with stress/genotype on early antidepressant efficacy

Aims Antidepressants are effective in the treatment of major depressive disorder (MDD), while many patients fail to respond to antidepressants. Both 5‐HT1A (HTR1A) and 5‐HT1B (HTR1B) receptors play an important role in antidepressant activity. Meanwhile, DNA methylation is associated with MDD and antidepressant efficacy. In this study we investigate the influence of HTR1A and HTR1B methylation combined with stress/genotype on antidepressant efficacy. Methods A total of 291 MDD patients and 100 healthy controls received the Life Events Scale (LES) and the Childhood Trauma Questionnaire (CTQ) as stress assessment. Eight single nucleotide polymorphisms (SNPs) of HTR1A and HTR1B involved in antidepressant mechanisms were tested. Methylation status in 181 cytosine‐phosphate‐guanine (CpG) sites of HTR1A and HTR1B were assessed. All MDD patients were divided into response (RES) and non‐response (NRES) after 2 weeks of antidepressant treatment. Logistic regression was conducted for interactions between methylation, NLES/CTQ score and genotype. Results Low HTR1A‐2‐143 methylation is connected with better antidepressant efficacy in subgroup. Low HTR1A‐2‐143 methylation combined with low CTQ score is related to better antidepressant efficacy. The interaction between high HTR1B methylation with the rs6298 AA/AG genotype affects better antidepressant efficacy. Conclusions HTR1A and HTR1B methylation combined with stress/genotype is associated with antidepressant efficacy.