A 30-year-old woman with well-documented PMDD undergoes investigation of her hormonal profile. Luteal-phase progesterone, estradiol, and allopregnanolone levels are all within normal limits. Based on current understanding of PMDD pathophysiology, her symptoms are best explained by:
- A Abnormally high circulating progesterone concentrations during the luteal phase
- B Absolute deficiency of serotonin throughout the menstrual cycle
- C Abnormal sensitivity of GABA-A receptors to normal fluctuations of allopregnanolone ✓
- D Pathological elevation of follicular-phase FSH
Correct answer: C. Abnormal sensitivity of GABA-A receptors to normal fluctuations of allopregnanolone
Explanation
Women with PMDD have normal ovarian steroid levels; their abnormality lies in an exaggerated CNS response, specifically altered sensitivity of GABA-A receptor complexes to the normal cyclical rise and fall of the progesterone metabolite allopregnanolone. This model explains why SSRIs work rapidly in PMDD and why the neurosteroid agents brexanolone and zuranolone are effective in postpartum depression. Option A is refuted directly by the normal hormone assay in the stem, which is the discriminating detail.
Reference: Kaplan and Sadock's Synopsis of Psychiatry, 12th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.