Limbic System‐Adrenal Cortex Regulation in Depression and Schizophrenia

&NA; Hypothalamo‐pituitary‐adrenal (HPA) activation and abnormal HPA regulatory mechanisms have been observed in depressed patients. Depressed and schizophrenic patients were studied to determine whether the HPA disturbances in depression are specific to this psychiatric illness or are mediated by nonspecific breakdown of psychological defense mechanisms. Despite the presence of severe ego defense breakdown and considerable secondary depressive symptomatology, the schizophrenic patients had normal HPA function. The depressed patients had elevated urine free cortisol excretion, high CSF cortisol levels, and did not show normal HPA suppression in response to dexamethasone. Within the depressed group significant correlations of HPA parameters were obtained with somatic features but not with ego breakdown features. After recovery depressed patients had more normal HPA function. The results indicate that HPA dysfunction can occur in association with primary depressive illness, that a psychoendocrine distinction can be made between primary depressive illness and secondary depressive symptomatology, and that psychological defense breakdown is not related to these neuroendocrine observations. Attention is drawn to the utility of urinary free cortisol measurement as a valuable index of HPA activation in psychoendocrine studies.