Sex Differences in Depression Caused by Early Life Stress and Related Mechanisms

Depression is a common psychiatric disease caused by various factors, manifesting with continuous low spirits, with its precise mechanism being unclear. Early life stress (ELS) is receiving more attention as a possible cause of depression. Many studies focused on the mechanisms underlying how ELS leads to changes in sex hormones, neurotransmitters, hypothalamic pituitary adrenocortical (HPA) axis function, and epigenetics. The adverse effects of ELS on adulthood are mainly dependent on the time window when stress occurs, sex and the developmental stage when evaluating the impacts. Therefore, with regard to the exact sex differences of adult depression, we found that ELS could lead to sex-differentiated depression through multiple mechanisms, including 5-HT, sex hormone, HPA axis, and epigenetics.