NEUROBIOLOGY OF SEASONAL AFFECTIVE DISORDER (SAD) AND LIGHT THERAPY

我们试图阐明季节性疾病的病理生理基础

We have attempted to clarify the pathophysiological basis of seasonal affective disorder (SAD) and the mechanism of action of light therapy. We previously reported on blunted hypothalamo-pituitary-adrenal (HPA) responses to the administration of corticotrophin (CRH), and the serotonin agonists m-CPP and ipsapirone (See Z01 MH 022689-02 CPB); and abnormally low circadian plasma prolactin levels. We reported that effective bright light therapy is associated with lowering of nocturnal core body temperature. This past year we continued in four ways: a) naturalistic studies of sleep, core body temperature and circadian plasma hormone profiles; b) measurement of plasma hormones following exercise stress; c) measurement of heart rate variability following orthostatic challenge; and, d) measurement of pituitary size in SAD patients (PTS) and healthy controls (CRTS). In the first set of studies, core body temperature from 22 PTS and 22 CRTS, studied both in winter and in summer were analyzed. Circadian plasma melatonin measures on these patients are presented in a separate report (Z01 MH 02687-02 CPB). Blood also was drawn to measures of thyroid function (TSH, T3, T4 and reverse T3) during nighttime sleep. An additional 23 PTS and 23 CRTS underwent sleep (including spectral analysis) and core body and skin temperature measurements this past winter. In PTS nocturnal core body temperature was significantly lower in winter than in summer but there was no seasonal difference in CRTS. Light therapy reduced nocturnal core body temperature (a replication of an earlier finding of ours) and the reduction was proportional to its antidepressant effects. Initial analysis of last winter's sleep recordings showed that PTS had significantly higher REM density and longer sleep cycles, but no other abnormalities. We found significantly elevated nocturnal values of TSH, T3, T4 and reverse T3 in PTS as compared with CRTS in winter (in both untreated and light treated conditions) and in summer. We also expanded the number of participants in an earlier study, in which it appeared that growth hormone levels in premenopausal women with SAD were blunted in winter (both in untreated and light-treated conditions) and in summer. An additional four PTS and four CRTS exercised on a treadmill to 90% of their oxygen saturation. Data analysis is underway and final results await completion of the summer phase of this study. In a third study, 22 PTS and 24 CRTS were studied in winter between 7:30 a.m. and 8:30 a.m. Heart rate variability was measured both at rest and 10 minutes after standing up and was analyzed for spectral power. Data analysis is underway and final results await completion of the summer phase of this study. Finally, we increased the number of participants in our ongoing study of magnetic resonance imaging of pituitary size by adding 8 additional PTS and 8 CRTS this past winter. Data analysis awaits completion of the summer phase of this study.