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Jiuan Su Terman, PhD; Michael Terman, PhD; Ee-Sing Lo, PhD; Thomas B. Cooper, MA

Arch Gen Psychiatry. 2001;58:69-75.

Background  We investigated a possible mechanism of action for the antidepressant response to light—phase advances of the circadian clock—by measuring the onset of melatonin secretion before and after light treatment in the morning or evening.

Methods  Plasma melatonin was sampled in 42 patients with seasonal affective disorder, in the evening or overnight while depressed and after 10 to 14 days of light therapy (10 000 lux for 30 minutes) when symptoms were reassessed.

Results  Morning light produced phase advances of the melatonin rhythm, while evening light produced delays, the magnitude depending on the interval between melatonin onset and light exposure, or circadian time (morning, 7.5 to 11 hours; evening, 1.5 to 3 hours). Delays were larger the later the evening light (r = 0.40), while advances were larger the earlier the morning light (r = 0.50). Although depression ratings were similar with light at either time of day, response to morning light increased with the size of phase advances up to 2.7 hours (r = 0.44) regardless of baseline phase position, while there was no such correlation for evening light. In an expanded sample (N = 80) with the sleep midpoint used as a reference anchor for circadian time, early morning light exposure was superior to late morning and to evening exposure.

Conclusion  The antidepressant effect of light is potentiated by early-morning administration in circadian time, optimally about 8.5 hours after melatonin onset or 2.5 hours after the sleep midpoint.

From the Clinical Chronobiology Program (Drs J. Terman and M. Terman), and the Department of Analytical Psychopharmacology (Dr Lo and Mr Cooper), New York State Psychiatric Institute, New York, and the Department of Psychiatry (Dr M. Terman), Columbia University, New York.

Corresponding author and reprints: Michael Terman, PhD, New York State Psychiatric Institute, 1051 Riverside Dr, Unit 50, New York, NY 10032 (e-mail: mt12{at}columbia.edu).

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