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J. John Mann, MD; Michael Stanley, PhD; P. Anne McBride, MD; Bruce S. McEwen, PhD

Arch Gen Psychiatry. 1986;43(10):954-959.

Abstract
• A statistically significant 28% increase in the mean (±SD) number of serotonin₂ receptors (127.8±13.4 vs 99.6 ±11.1 fmol/mg of protein) and a 73% increase in β-adrenergic receptor binding (14.5±1.5 vs 8.4 ±1.5 fmol/mg) was found in the frontal cortices of violent suicide victims compared with matched controls. No significant differences were found in the number of serotonin_, binding sites (109.5 ± 13.4 vs 99.9 ±8.8 fmol/mg). We have previously reported a reduced density of presynaptic tritiated imipramine binding sites on serotonergic nerve terminals in the frontal cortices of suicide victims. These data support the hypothesis that suicide completed by violent methods is associated with reduced presynaptic serotonergic activity that has generated compensatory upregulation of the postsynaptic serotonin² receptor sites. The increase observed in β-adrenergic binding suggests that there may also be a concomitant reduction in presynaptic noradrenergic activity associated with suicide. If antidepressant pharmacotherapies specifically downregulate cortical β-adrenergic and/or serotonin₂ receptors in depressed subjects, as has been demonstrated in animal studies, and since these effects would be in the opposite direction of the receptor changes found in suicide victims, they may account for the therapeutic action of antidepressants on suicidal behavior and depressive disorders.

Author Affiliations
From the Laboratory of Psychopharmacology, Department of Psychiatry, Cornell University Medical College, New York (Drs Mann and McBride); the Departments of Psychiatry and Pharmacology, College of Physicians and Surgeons of Columbia University, New York (Dr Stanley); and the Laboratory of Neuroendocrinology, Rockefeller University, New York (Dr McEwen).

Footnotes
Accepted for publication May 7, 1986.

Reprint requests to Laboratory of Psychopharmacology, Department of Psychiatry, Cornell University Medical College, 1300 York Ave, New York, NY 10021 (Dr Mann).

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