BIOLOGICAL MECHANISMS OF THE ANTIDEPRESSANT EFFECTS OF SLEEP DEPRIVATION

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Total sleep deprivation for one night induces temporary remissions in sixty percent of patients with major depression; it can also induce mania in bipolar patients. Furthermore, as little as one hour sleep can trigger depression in patients who have improved after sleep deprivation. Thus, sleep appears to have a depressant effect and wakefulness a mood-elevating effect. These observations have practical implications for the management of affective illness. For example, some patients' depression can be treated with sleep deprivation, and sleep disruption is sometimes an identifiable and preventable cause of mania. The purpose of this project is to attempt to identify biological mechanisms of the antidepressent effects of sleep deprivation. Identification of biological mechanisms would increase understanding of the pathogenesis of depression and mania and could be expected to lead to new, rapidly activating drug treatments for depression and mania. The current project is designed to test a hypothesis that thermoregulatory mechanisms underlie the mood-altering effects of sleep and sleep deprivation. The hypothesis is based on our observation that many of the physiological responses to sleep resemble responses to heat exposure. Like heat exposure, sleep onset stimulates secretion of sweat, prolactin (PRL) and growth hormone (GH), and it inhibits metabolic heat production and secretion of thyrotropin (TSH) and triiodothyronine (T3). Like cold exposure, sleep deprivation has opposite effects. We are testing the hypothesis that the heat-like property of sleep and the cold-like property of sleep deprivation are responsible for their clinical and neuroendocrine effects in depressed patients. According to this hypothesis, a warm environment, compared with a cool environment, should blunt the antidepressant and neuroendocrine effects of sleep deprivation. Patients are sleep-deprived on one occasion in an ambient temperature of 33 degrees C, and on another occasion in an ambient temperature of 18 degrees C. Twelve patients have been studied, and the results are consistent with the hypothesis. After sleep deprivation in the cool condition compared with the warm condition antidepressant effects were greater (p<0.03), augmentation of TSH secretion was greater (p<0.05), augmentation of T3 was greater (p<0.01), and suppression of PRL was greater (p<0.03). The results show that the depressant and neuroendocrine effects of sleep can be mimicked by heat exposure. Animal studies being carried out in our laboratory could be interpreted as providing further evidence that cooling is antidepressant (ZO1 MH 02294-06 CP). In hamsters, chronic treatment with three classes of antidepressant drugs (a serotonin reuptake inhibitor, a monoamine oxidase inhibitor, and lithium) lower brain temperature 0.5 degrees C during sleep. In contrast, the antimanic agent, haloperidol, raises brain temperature during sleep. Finally, in patients with winter depression, phototherapy lowers rectal temperature 0.5 degrees C during sleep.