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Sex Differences in Depressive Response During Monoamine Depletions in Remitted Depressive Subjects

Francisco A. Moreno, M.D.; Cynthia A. McGahuey, B.A.; Marlene P. Freeman, M.D.; and Pedro L. Delgado, M.D.

Objective: Although sex differences in the prevalence of depression are well known, the effects of sex on the underlying mechanisms of illness and on antidepressant action remain less clear. Tryptophan depletion and catecholamine depletion (via a-methylparatyrosine [AMPT] administration) are broadly utilized methods for studying the effects of the safe and transient reduction of serotonin and catecholamine neurotransmission, respectively. The present study assessed the effects of sex on the mood response during acute monoamine depletion.

Method: Data on Hamilton Rating Scale for Depression (HAM-D) scores during depletion tests were analyzed retrospectively in 59 subjects (41 women, 18 men) who underwent tryptophan depletion and 39 subjects (25 women, 14 men) who underwent catecholamine depletion. All subjects were in remission from a DSM-IV-defined major depressive episode. Data reviewed included subjects enrolled between November 1993 and November 1997.

Results: Significant increases in HAM-D scores were observed in response to both depletion procedures, with a similar magnitude of change. Analysis of variance with repeated measures of HAM-D scores revealed a significant main effect of time for tryptophan depletion (F = 7.31, df = 3, p < .01) and for catecholamine depletion (F = 9.61, df = 4, p < .01). Time-by-sex interaction was significant for tryptophan depletion (F = 4.04, df = 3, p = .01), but not for catecholamine depletion (F = 0.75, df = 4, p = .57). Depressive symptoms were significantly greater in women during tryptophan depletion (t test p < .01), while no significant sex differences were found during catecholamine depletion.

Conclusions: These findings suggest that the effect of sex in depressive vulnerability may be related to differential sex effects in monoaminergic function.

(J Clin Psychiatry 2006;67:1618-1623)

Received June 6, 2005; accepted April 13, 2006. From the Department of Psychiatry, College of Medicine, University of Arizona Health Sciences Center, Tucson (Drs. Moreno and Freeman and Ms. McGahuey); and the Department of Psychiatry, University of Texas Health Sciences Center, San Antonio (Dr. Delgado).

Supported by the University of Arizona College of Medicine Dean's Physician Scientist Career Development Award (Dr. Moreno) and National Institute of Mental Health grant R01 MH48977 (Dr. Delgado).

Presented at the 29th annual meeting of the Society for Neuroscience, New Research Abstract 855.16, November 1999, Miami Beach, Fla.; and the 37th and 38th annual meetings of the American College of Neuropsychopharmacology, December 1998, Las Croabas, Puerto Rico, and December 1999, Acapulco, Mexico.

Financial disclosure is listed at the end of this article.

The authors thank the Arizona Hispanic Center of Excellence for logistics support; Candace Fogel, R.N., for assistance with data management; and Jeri Lizabeth Fickelman, Ph.D., for editorial contribution.

Corresponding author and reprints: Francisco A. Moreno, M.D., Department of Psychiatry, College of Medicine, University of Arizona Health Sciences Center, 1501 N. Campbell Ave., Suite 7303, Tucson, AZ 85724 (e-mail: