SEROTONIN 1A RECEPTORS, MELATONIN, AND THE PROPORTIONAL CONTROL THERMOSTAT IN PATIENTS WITH WINTER DEPRESSION

Background: In patients with seasonal affective disorder, light treatm ent lowers core temperature during sleep in proportion to its antidepr essant efficacy. The regulation of the level of core temperature durin g sleep is linked with a proportional control thermostat in the centra l nervous system whose operation appears abnormal in patients with sea sonal affective disorder. Because both melatonin and serotonin 1A rece ptor activation also lower core temperature, we investigated the relat ionship between ii) endogenous melatonin and core temperature profiles , (2) the proportional control thermostat, and (3) the core hypothermi c response to the serotonin 1A receptor partial agonist ipsapirone hyd rochloride in patients with seasonal affective disorder and healthy co ntrols. Methods: Eighteen patients with seasonal affective disorder an d 18 controls first completed a 24-hour study in which their melatonin profiles were characterized. Subjects then returned 3 to 5 days later for the first of 2 drug challenges (ipsapirone hydrochloride, 0.3 mg/ kg, or placebo), each separated by 3 to 5 days. Overnight rectal and f acial temperatures were recorded before and after each drug challenge. Results: The magnitudes of the core hypothermic responses to ipsapiro ne were (1) not different between groups and (2) independently correla ted with both the levels of the previous nights' core temperature-mini ma (P = .002) and the amounts of nocturnal melatonin secreted (P<.001) . Conclusion: The daytime regulation of core temperature by serotonin 1A receptors appears normal in seasonal affective disorder. The magnit ude of serotonin 1A receptor-activated hypothermia is governed by a ce ntral nervous system proportional control thermostat whose operation a ppears modulated by both melatonin and the level of the core temperatu re minimum.