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Robert D. Levitan, MD; Allan S. Kaplan, MD; Gregory M. Brown, MD, PhD; Franco J. Vaccarino, PhD; Sidney H. Kennedy, MD; Anthony J. Levitt, MD; Russell T. Joffe, MD

Arch Gen Psychiatry. 1998;55:244-249.

Background  There is emerging evidence of serotonergic dysfunction in patients with seasonal affective disorder (SAD). We examined central serotonergic function in female patients with SAD (fall-winter pattern) by means of neuroendocrine and subjective responses to the postsynaptic serotonin receptor agonist m-chlorophenylpiperazine.

Methods  Using a double-blind, randomized, placebo-controlled design, we assessed neuroendocrine and subjective responses to m-chlorophenylpiperazine (0.1 mg/kg intravenously) and placebo in 14 unmedicated female patients with SAD in the depressed state and 15 female normal controls. All testing was done in the fall-winter months and during the follicular phase of the menstrual cycle. Plasma prolactin and cortisol levels were used as neuroendocrine measures, while subjective responses were assessed by means of visual analog scales of 10 mood states.

Results  On the basis of net responses to m-chlorophenylpiperazine (placebo effects subtracted from drug effects), patients with SAD exhibited blunted prolactin responses and less sadness than normal controls in response to the drug. When order of presentation of drug and placebo was taken into consideration, altered "calm" and "high" responses were also found in the patient group.

Conclusion  Evidence of dysfunction at or downstream to central serotonergic receptors in female patients with SAD confirms and extends findings from previous research.

From the Clarke Institute of Psychiatry (Drs Levitan, Brown, Vaccarino, Kennedy, Levitt, and Joffe) and The Toronto Hospital (Dr Kaplan), Department of Psychiatry, University of Toronto, Toronto, Ontario. Dr Levitt is now with the Mood Disorders Clinic, Sunnybrook Hospital, Department of Psychiatry, University of Toronto. Dr Joffe is now with the Departments of Medicine and Psychiatry, McMaster University, Hamilton, Ontario.

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