Adrenergic receptors in premenstrual dysphoric disorder: I. Platelet α 2 receptors: G i protein coupling, phase of menstrual cycle, and prediction of luteal phase symptom severity

Abstract

Background: Abnormal α 2-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 α 2AR function. Previous studies on α 2AR function during phases of the menstrual cycle in controls and PMDD patients are inconsistent. Methods: α 2AR 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 α 2AR binding parameters between phases of menstrual cycle in PMDD women. α 2AR density and symptom severity were inversely related during the follicular phase in controls and patients. During luteal phase, α 2AR density correlated positively with symptom severity in patients. High follicular α 2AR density predicted more severe luteal symptoms in PMDD patients. Conclusions: These findings are discussed in view of the molecular biology of α 2AR, and their role in PMDD, anxiety, and depressive disorders.