Genes involved in neuroplasticity and stressful life events act on the short-term response to antidepressant treatment: a complex interplay between genetics and environment

Abstract

Objective: During the last few years, an increasing number of studies have focused on the association between neuroplasticity and affective disorders. The aim of the study is to evaluate the interactive effect of stressful life events (SLEs) and genes involved in neuroplasticity (BDNF and ST8SIA) on the short-term response to antidepressant treatment.

Methods: A total of 114 patients affected by mood or anxiety disorders under antidepressant treatment were enrolled in the study. We evaluated the interactive effects of three BDNF single-nucleotide polymorphisms (SNPs) and five ST8SIA SNPs and SLEs at different time points (childhood SLEs, SLEs at illness onset, and SLEs reported over the last preceding treatment) over 1-month of antidepressant treatment.

Results: Carriers of some genetic variants in both BDNF and ST8SIA had a slower response to antidepressants if non-exposed to the onset SLEs, whereas they had a similar trend compared with the carriers of the opposite variant if exposed (allelic analysis: BDNF p = 0.00003, p = 0.00609; ST8SIA p = 0.04, p = 0.033). The BDNF haplotype analysis confirmed this trend (p = 0.00016).

Conclusions: Though our results are limited by the small sample size, variants in BDNF and ST8SIA may slow down the early response to antidepressants in subjects non-exposed to stressors at the illness onset, with a remarkable gene-environment interaction.

Keywords: BDNF; ST8SIA2; antidepressant; stressful life events.