A number of hormonal abnormalities have been reported in patients with affective disorders. Many of these abnormalities have been shown not to be specific for depression, but rather to be associated with a number of stress-related conditions. Advances in the field of neuroendocrinology, including the development of the radioimmunoassay technique and the availability for clinical studies of several of the hypothalamic hormones has allowed new approaches to studying endocrine aspects of depression. Among the most frequently reported hormonal abnormalities in depression have been the early escape from dexamethasone suppression observed in some depressed patients and the insufficient TSH response to TRH administration which has also been observed in some depressed patients. We will extend neuroendocrine studies of depression by examining hormonal responses to a neuroendocrine test battery consisting of the sequential administration of saline, insulin, TRH, and dexamethasone. After TRH administration, a battery of hormones: TSH, T3, T4, LH, GH, prolactin, cortisol and testosterone (males) or estradiol (females), will be monitored. These studies should extend the descriptions of hormonal response abnormalities in depression and should clarify the mechanisms underlying these abnormalities. We will also initiate studies of thermoregulation in patients with primary affective disorder. Abnormalities in response to heat and cold stress may point to hypothalamic central nervous system dysfunction. Other adaptive responses to temperature stress such as shivering and vasoconstriction, will also be examined. These studies are important in evaluating an additional method for detecting physiological response mechanisms in depression.