Evidence for physiological effects of hypercortisolemia in psychiatric patients

Although some psychiatric patients may have a disorder of hypothalamic-pituitary-adrenal (HPA) function equal in character and severity to that noted in milder cases of Cushing's disease, it is generally accepted that such patients do not show Cushingoid stigmata. This conclusion, however, appears to be based more on clinical observation than on the results of formal scientific investigation. Since some depressed patients appear to overlap with Cushing's disease patients in incidence of such signs and symptoms as amenorrhea, hypertension, sleep disturbance, and insulin resistance, we were interested in examining whether a group of psychiatric patients showing evidence of marked nonsuppression might not also show physiological changes consonant with the effect of glucocorticoid excess. Nonsuppressors selected on this basis differed slightly from a matched suppressor control group on percentage of polyneutrophils and lymphocytes in blood. A discriminant function constructed from blood sample measurements of 12 factors and systolic/diastolic blood pressure successfully predicted suppressor or nonsuppressor status in the original and in an independent group of psychiatric patients. A comparison group of Cushing's disease patients was also successfully reclassified on the basis of the discriminant function. These data are interpreted as evidence for a subtle physiological effect of HPA dysregulation and suggest that behavioral symptom complexes may be similarly shaped by changes in this neuroendocrine system. The long-term functional significance of such changes is at present speculative.