The molecular basis for sex differences in depression susceptibility

Depression is a prevalent, devastating psychiatric disorder which women are twice as likely to suffer as men. Yet, until recently, most of the mechanistic studies shedding light on the molecular pathways involved in depression have focused on males, both animals and humans. It has been established that women have a more sensitive stress response, and that sex hormones contribute to depression onset. Recent genome-wide studies on human and mouse brain tissue have revealed that the overlap in the genes regulated by depression or chronic stress, respectively, between the sexes is surprisingly low. Such unbiased comprehensive screening approaches combined with advanced bioinformatics and in vivo validation studies enable identifying truly novel target genes that contribute to sex differences in depression susceptibility. Furthermore, recent studies have demonstrated sex bias in transgenerational passage of the effects of stress to the offspring. Elucidating the sex-specific mechanisms contributing to the development of depression can help design better diagnostic and therapeutic tools aimed at normalizing the unique abnormalities of each gender.