Neuroendocrine markers of serotonin responsivity in depression

1. Studies of the biochemical mechanism of action of antidepressant drugs show that virtually all drugs, regardless of acute biochemical effects, result in the down regulation of CNS beta-1 adrenergic, serotonin-2 (5HT2), and perhaps 5HT1A receptors in rats in a time course which parallels the onset of antidepressant action in patients with major depressive disorder. 2. Recently, neuroendocrine techniques have been described which allow the study of 5HT receptor subtypes in man. These include fenfluramine-induced changes in ACTH, cortisol and prolactin secretion (perhaps for 5HT2 receptors) and ipsapirone-induced changes in ACTH and cortisol (for 5HT1A receptors). 3. Depressed subjects treated with antidepressants down regulate these markers of both 5HT2 and 5HT1A receptors in a time course consistent with their recovery from depression. 4. Studies in progress are attempting to demonstrate links between these receptor changes and clinical antidepressant responses.