Hormonal Cycles, Brain Network Connectivity, and Windows of Vulnerability to Affective Disorder

The rate of affective disorder is substantially higher in women than in men, and considerable evidence points to the actions of ovarian hormones in mediating this disparity. In this Opinion, we discuss the hypothesis that cyclic changes in ovarian hormone levels produce cyclic alterations in connectivity between the intrinsic networks of the brain. These alterations produce specific temporal windows within the menstrual cycle when internetwork connectivity is increased, associated with increased stress reactivity and better memory for unpleasant, arousing events, leading to increased negative mood and susceptibility to affective disorder. Our windows of vulnerability model offers insights for both treatment of affective disorder and research on sex differences in the brain.