Allopregnanolone and Dynamic GABA-A Receptor Plasticity in Selective Serotonin Reuptake Inhibitor Responsive Premenstrual Dysphoric Disorder

The goals of this multi-site randomized placebo controlled trial (RCT) are to characterize three aspects of neuroactive steroid (NAS) dysfunction across the luteal phase of the menstrual cycle in premenstrual dysphoric disorder (PMDD) compared with healthy controls, and to assess how Selective serotonin reuptake inhibitors (SSRI) treatment in PMDD impacts: 1) GABAergic NAS fluctuations, particularly positive allosteric modulators (PAMs: allopregnanolone (ALLO), pregnanolone) and negative allosteric modulators (NAMs: isoallopregnanolone, epipregnanolone) of the GABAA receptor (GABAAR), 2) GABAAR subunit expression, and 3) neurosteroidogenic enzyme expression.