A Longitudinal Study of Serotonergic Function in Depression

Several reports have described abnormal neuroendocrine responses to serotonergic challenge tests in depression, but few have studied depressed patients followed longitudinally. In order to determine whether blunted prolactin responses to clomipramine challenge is a “state” vs. “trait” marker in depression, we applied this challenge paradigm to 20 patients with Major Depression prior to treatment and at three additional time points following response to desipramine: at the completion of acute treatment; at the end of the continuation phase of treatment; and after a minimum of three weeks “washout” following the discontinuation of treatment. The prolactin response to clomipramine challenge was blunted in depressed patients compared with matched healthy control subjects, at each time point over the longitudinal course of their illness and recovery. Challenge test results in depressed patients did not change after response to acute desipramine therapy, at the conclusion of the continuation phase of treatment, or while in a medication-free state of remission. Blunted prolactin response to clomipramine challenge persists in depressed patients after recovery from acute illness, and may reflect an underlying biological vulnerability.