Abstract
24-hour urines collected on one or more occasions in each of twenty-six female patients with affective disorders were analysed for 3',5' cyclic adenosine monophosphate (cyclic A.M.P.). In healthy controls the 24-hour excretion was 2282 nmole of cyclic A.M.P. In thirteen cases where an initial depression improved after treatment the mean cyclic A.M.P. excretion rose from 523 to 1283 nmole per 24 hours. In all patients from whom two collections were made the change in cyclic-A.M.P. excretion reflected the alteration in the clinical picture —improvement in depression being consistently associated with an increase in cyclic A.M.P., while the trend was reversed in patients moving away from mania. It is suggested that intracellular cyclic-A.M.P. deficiency is related to depressive illness and that a striking increase leads to mania. This hypothesis explains both the somatic signs and symptoms of depression and the laboratory findings, and it is supported by the ability of tricyclic antidepressants to inhibit cyclic-A.M.P. degradation and by the ability of cyclic A.M.P. to reverse reserpine-induced ptosis (an animal model for depression).