Desmopressin Normalizes the Blunted Adrenocorticotropin Response to Corticotropin-Releasing Hormone in Melancholic Depression: Evidence of Enhanced Vasopressinergic Responsivity

Major depression is associated with significant disturbance in hypothalamic-pituitary-adrenal axis functioning, including blunted release of ACTH in response to CRH infusion. Eight melancholic depressives and eight matched healthy comparison subjects underwent, in random order, the following challenges: placebo, CRH, CRH+DDAVP. Blood for ACTH and cortisol estimation was drawn at −15, 0, 15, 30, 45, 60, 90, and 120 min. A blunted release of ACTH, in response to CRH challenge, was observed in depression (P < 0.01), whereas maximal cortisol responses in both groups were similar, despite elevated baseline levels in depression (P < 0.05). The combined CRH/DDAVP infusion produced similar ACTH and cortisol release in both groups. These results suggest that melancholic depression is associated with enhanced pituitary vasopressinergic responsivity.