582 BIOL PSYCHIATRY 1992;31-582-590 Nocturnal Urinary Excretion of 6-Hydroxymelatonin Sulfate in Prepubertal Major Depressive Disorder G. Scott Waterman, Neal D. Ryan, James M. Perel, Ronald E. Dahl, Boris Birmaher, Douglas E. Williamson, Christopher R. Thomas, and Joaquim Puig-Antich* Levels of the melatonin metabolite, 6-hydroxymelatonin sulfate, were measured in over- night urine from 31 prepubertai children with major depressive disorder and 15 normal control children with very. low family loading for affective disorder. The two groups did not differ with regard to their nocturnal excretion of this compound, nor was any de- pressive subgroup identified whose 6-hydroxymelatonin sulfate excretion differed from that of the control group. Previous studies of pineal function in depression are reviewed and discussed in the context of the present investigation. Introduction The physiological role in humans of melatonin, the principal hormone secreted by the pineal gland, remains to be explained. It has, however, been extensively studied, and a good deal is known about its synthesis, secretion, and metabolism (for a recent review see Reiter 1989). Its role in development is unresolved. Although, after infancy, melatonin plasma concentrations generally fall with advancing age, the effect in humans of puberty per se remains controversial (Waldhauser et al 1984; Reiter 1989). The relationship between the pineal gland and mental illness has been a subject of speculation for centuries (Miles and Philbrick 1988). More recently, research has explored possible derangements in pineal function in specific clinical psychiatric conditions, including depression. Melatonin is produced and released from the pineal in response to release of norepi- nephrine from postganglionic sympathetic fibers whose cell bodies reside in the superior cervical ganglion. The action of norepinephrine on pinealocytes is mediated by beta adrenoreceptors (Deguchi and Axelrod 1972). Findings of altered melatonin secretion in depression have thus been interpreted as possibly indicative of catecholaminergic and/or beta adrenoreceptor abnormalities (Brown et al 1985; Mclntyre et al 1986). Because melatonin is secreted almost entirely during periods of darkness (due to the suppressive effects of daylight), studies of this hormone in depression have generally From the Department of Psychiatry. Umverslty of Pittsburgh School of Medtcme, Western Psychlatnc Institute and Chnic, Pittsburgh, PA. Address repnnt requests to G Scott Waterman, M.D, Chdd and Adolescent Mood Program, Western Psychiatric Institute and Chntc, 3811 O'Hara Street, Pittsburgh, PA 15213 *~ p,,,~. A,.,,,.h ,~ deceased Rece,ved May 16. 1991; revtsed October ! !, 1991 © 1992 Society of Biological Psychmtry 0006-3223/92/$05 O0