GABAergic neuroactive steroids and network states: relevance to peripartum depression.

Abstract

The Food and Drug Administration's approval of allopregnanolone analogs, which function as positive allosteric modulators at GABA_A receptors, for the treatment of postpartum depression is a major advance in neuroscience research and psychiatry. Neuroactive steroid-based antidepressant effects likely involve the ability to restore network states within and between emotional processing hubs. Here we review the role for steroid hormones and neuroactive steroids, particularly progesterone and allopregnanolone, in preparing the brain for the transition to motherhood. We highlight preclinical and clinical findings which elucidate the networks that are altered in the maternal brain. Further, we summarize the changes in brain networks implicated in peripartum depression. Preclinical and clinical evidence support disrupted network states contributing to peripartum depression and a role for altered GABAergic and neuroactive steroid signaling in its underlying pathophysiology. Recent advances continue in the identification of biomarkers for predicting peripartum depression and the development of the next generation of treatments offer additional promise for the prevention or treatment of peripartum depression.