Hormonal regulation of circuit function: sex, systems and depression

Major depressive disorder (MDD) is a debilitating chronic illness that is two times more prevalent in women than in men. The mechanisms associated with the increased female susceptibility to depression remain poorly characterized. Aberrant neuronal oscillatory activity within the putative depression network is an emerging mechanism underlying MDD. However, innate sex differences in network activity and its contribution to depression vulnerability have not been well described. In this review, current evidence of sex differences in neuronal oscillatory activity, including the influence of sex hormones and female cycling, will first be described followed by evidence of disrupted neuronal circuit function in MDD and the effects of antidepressant treatment. Lastly, current knowledge of sex differences in MDD-associated aberrant circuit function and oscillatory activity will be highlighted, with an emphasis on the role of sex steroids and female cycling. Collectively, it is clear that there are significant gaps in the literature regarding innate and pathologically associated sex differences in network activity and that the elucidation of these differences is invaluable to our understanding of sex-specific vulnerabilities and therapies for MDD.