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Timothy D. Brewerton, MD; Edward A. Mueller, MD; Michael D. Lesem, MD; Harry A. Brandt, MD; Bonnie Quearry, MS; D. Ted George, MD; Dennis L. Murphy, MD; David C. Jimerson, MD

Arch Gen Psychiatry. 1992;49(11):852-861.

Abstract
• Preclinical and clinical evidence supports a theory of serotonin (5-hydroxytryptamine [5-HT]) dysregulation in bulimia. We therefore studied the prolactin (PRL) and cortisol responses following challenges with the postsynaptic 5-HT receptor agonist m-chlorophenylpiperazine (m-CPP), 0.5 mg/kg orally, the 5-HT precursor L-tryptophan, 100 mg/kg intravenously, and placebo in a group of 28 normal weight bulimic patients and 16 healthy controls. Patients with bulimia, regardless of the presence of major depression, had significantly blunted PRL responses following m-CPP administration compared with those in controls. In contrast, only bulimic patients with concurrent major depression had significantly blunted PRL responses following L-tryptophan administration compared with those in nondepressed bulimic patients and controls. Cortisol responses following m-CPP were not significantly different for bulimic patients vs controls, although there was a trend toward blunted cortisol responses following L-tryptophan administration in the depressed bulimic patients. These differences in neuroendocrine responses were not related to differences in age, percent of average body weight, medications, time of day, peak plasma drug levels, or baseline estradiol levels. Seasonal variations in PRL responses to both agents were identified, although covariation for season did not alter the group differences. The PRL responses following m-CPP administration were inversely correlated to baseline cortisol levels in the bulimic patients, but not in the controls, suggesting a dampening effect by hypothalamic-pituitaryadrenal axis dysfunction on postsynaptic 5-HT receptor sensitivity. The reasons for the differing hormonal responses to these two serotonergic agents may relate to differential involvement of presynaptic and postsynaptic mechanisms, 5-HT receptor subtypes, and anatomical loci of action. The blunted PRL responses to m-CPP administration suggest that postsynaptic 5-HT receptor sensitivity is altered in bulimia nervosa, and that similar alterations in 5-HT receptors at or above the level of the hypothalamus may contribute to binge eating and other behavioral symptoms.

Author Affiliations
From the Section on Biomedical Psychiatry, Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, Md. Dr Brewerton is now with the Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston. Dr Mueller is now with the Rutland (Vt) Mental Health Center. Dr Lesem is now with the Department of Psychiatry, University of Texas Medical School Hospital, Houston. Dr Brandt is now with the Department of Psychiatry, University of Maryland School of Medicine, Baltimore. Dr George is now with the Laboratory of Clinical Studies, National Institute of Alcoholism and Alcohol Abuse, Bethesda, Md. Dr Jimerson is now with the Department of Psychiatry, Beth Israel Hospital and Harvard Medical School, Boston, Mass.

Footnotes
Accepted for publication August 26, 1991.

Reprint requests to Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, 171 Ashley Ave, Charleston, SC 29425-0742 (Dr Brewerton).

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