Early Life Stress and Response to Antidepressant Treatment

Abstract

Early life stress (ELS) is a significant risk factor for increased susceptibility to future stress and to psychiatric disorders such as major depressive disorder (MDD). Studies have shown that MDD patients with a history of ELS respond poorly to typical antidepressant treatment but respond well to atypical antidepressant treatment. The mechanisms by which ELS leads to altered treatment response remains unclear. In both humans and mice, the nucleus accumbens (NAc) is implicated in depression- and anxiety-like behaviors resulting from ELS. We hypothesize that ELS alters transcriptional patterns in the NAc and consequently, increases nonresponse to standard antidepressant treatment. Here, we analyzed the gene expression changes in the NAc of ELS mice treated with typical vs. atypical treatment and compared them to their behavioral changes before and after treatment. Our results suggested that ELS, as well as sex, are important factors in changing transcriptional patterns and predicting treatment nonresponse. Ultimately, this research has immense potential for innovations in treatment that take into account the heterogeneity of depression and allow for all types of patients to receive efficacious treatment.