Adrenergic receptors in premenstrual dysphoric disorder: I. Platelet α₂ receptors: G(i) protein coupling, phase of menstrual cycle, and prediction of luteal phase symptom severity

Background: Abnormal α₂-adrenergic receptor (AR) function is implicated in anxiety and depressive disorders. Premenstrual dysphoric disorder (PMDD) is characterized by anxiety and depressive symptoms, which may be associated with changes in α₂AR function. Previous studies on α₂AR function during phases of the menstrual cycle in controls and PMDD patients are inconsistent. Methods: α₂AR function was examined in 16 PMDD patients and 15 controls during the follicular phase, and in 10 PMDD patients during late luteal phase. Antagonist-measured maximum binding capacity, agonist- measured receptor density in high- and low-conformational states, and agonist affinity to both states were measured. Coupling efficiency to G(i) protein was estimated. Results: There were no significant differences in coupling efficiency. PMDD patients had significantly low antagonist affinity; there were no differences in other binding parameters. There were no changes in α₂AR binding parameters between phases of menstrual cycle in PMDD women. α₂AR density and symptom severity were inversely related during the follicular phase in controls and patients. During luteal phase, α₂AR density correlated positively with symptom severity in patients. High follicular α₂AR density predicted more severe luteal symptoms in PMDD patients. Conclusions: These findings are discussed in view of the molecular biology of α₂AR, and their role in PMDD, anxiety, and depressive disorders.