Adrenergic receptors in premenstrual dysphoric disorder: I. Platelet α2 receptors: Gi 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 Gi 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.