The goals of this project are to detect and accurately describe menstrually-related mood disorders, explore their pathophysiology and response to pharmacological and environmental manipulation, and to document the relationship between reproductive endocrine change and disorders of mood as a way of further investigating the neurobiology of psychiatric illness. In the past year we have identified: 1) the ability of GnRH analogue (Lupron) to eliminate premenstrual syndrome during the second month of administration in some but not all patients; 2) the precipitation of significant mood symptoms by either estrogen or progesterone in several patients whose symptoms were successfully treated by GnRH analogue; 3) a dramatic (25-30%) decrease in global cerebral blood flow during progesterone administration compared with estrogen administration or GnRH analogue alone; 4) significant improvement in symptoms of PMS during the luteal phase in patients receiving m-CPP, a mixed serotonin agonist; 5) significantly reduced plasma vasopressin in patients with premenstrual syndrome across the menstrual cycle; 6) significant albeit subtle increased alcohol consumption across the menstrual cycle in patients with PMS compared with controls; 7) the therapeutic efficacy of fluoxetine in ten of 13 patients with PMS; 8) the absence of a difference in magnesium retention in patients with PMS compared with controls.