I ! 56 BIOL PSYCHIATRY 1990;27:1156-1164 Multiplicity of Depressive Episodes: Phenomenological and Neuroendocrine Correlates George N.M. Gurguis, James H. Meador-Woodruff, Roger F. Haskett, and John F. Greden Sixty-four patients with a Research Diagnostic Criteria (RDC) diagnosis of major de- pressive disorder were categorized into three groups based on their number of depressive episodes (DE): Gr I (1 DEp, n = 16, Gr 11 (2-4 DE), n = 25; and Gr Ill. (5 o'r more DE), n = 23. All patients were nonsuppressors after Img dexamethasone suppression test (DST) prior to the start of treatment. Patients were monitored during the course of their treatment using serial Hamilton Depression scores and post-DST plasma cortisol levels. A proportionately equai ~ number of patients in the three groups ~..,~a a favorable outcome, i.e., the number of depressive epdsodes did no~: predict recove~ 7. Despite fa- vorable clinical outcome, patients with kigher numbers ~f depressive episodes hoxl sig- nificantly higher post-DST plasma cortisc, l levels that were above the suppressive: range (greater than 5 ttg/dl). Patients with a higher number of depressive episodes had a significantly shorter duration of index episode and were younger at first depressive episode than patients in the other two groups. These results, however, were confounded with polarity, with a higher nv.mber @ bipolars in Gr iil than in the other two groups. Results are discussed in light of phezromenological a,Td psychoendocrine findings of earfier studies. Introduction The chronic, episodic, and recurrent nature of major depressive disorder represents a prominent feature, in its phenomenology. Therefore, studying the effect of time course on the phenomenology and neuroendocri~Jology of this illness could help further our understanding of the underlying pathopbysiological mechanisms and prognostic aspects of depression. Particularly relevant to ~he neuroendocrinology of depression is the reg- ulation of the hypothalamic-pituitary-adrenocortical (HPA) axis over the course of time. Hypothetically, the dysregulation of this system may change as the illness becomes progressively chronic. From the Clinical Studies Unit of the Michigan Depression Program, Department of Psychiauy, University of Michigan, Ann Arbor, MI. Address reprint requests to Dr. George Gurguis, Biological Psychiatry Branch, NIMH, Bldg I0, Room 3S239, 9000 Rockville Pike, Betbesda, MD 20892. Received January 20, 1989; revised October 7, 1989. Supported in part by NIMH Grant I R0 !-40216-01 (J.F.G.) and the Depa~.ment of Psychiatry and the Theophile Raphael Fund at the University of Michigan Medical Center. Presented in part at the 41st Annual Meeting of thc Society of Biological Psychiatry, Washington, D.C., May 7-11, 1986. This article is in the Public Domain. 0006-3223/90/$00.00