Vasopressin, major depression, and hypothalamic–pituitary–adrenocortical desensitization

Abstract

Background: The hypothalamic neuropeptide arginine vasopressin is thought to play an important role in the pathophysiology of affective disorders and the hyperactivity of the hypothalamic–pituitary–adrenocortical system that frequently accompanies them. Postmortem studies as well as clinical investigations have described elevated levels of vasopressin in the brain and plasma of depressed patients, and this finding has been suggested to contribute to depressive symptomatology. Methods: The case of a 47-year-old patient displaying chronically elevated plasma vasopressin levels due to paraneoplastic vasopressin secretion by an olfactory neuroblastoma and the first episode of major depression is presented. Results: Depressive symptoms improved markedly after surgical resection of the tumor and subsequent normalization of plasma vasopressin levels. Unexpectedly, neither corticotropin nor cortisol secretion could be stimulated by an intravenous corticotropin-releasing hormone challenge under the condition of chronically elevated plasma vasopressin levels in this patient. Conclusions: Chronically elevated plasma vasopressin levels may induce depressive symptomatology, and—in contrast to the potent corticotropin secretagogue effects of acute vasopressin administration—lead to a marked desensitization of the hypothalamic–pituitary–adrenocortical system.