Recovery from Major Depression Is Not Associated with Normalization of Serotonergic Function

Background: Plasma prolactin response to fenfluramine, a serotonergic agent, is typically blunted in moderately to severely depressed adults when compared to healthy controls. It is not clear, however, whether this dysregulation represents an acute change during symptomatic depression or a chronic disturbance. Methods: In the current study, the prolactin responses to -fenfluramine (weight-adjusted oral dose) of 29 adults who had a history of at least one major depressive episode (DSM-III-R criteria), but not during the past year, were compared to the prolactin responses of 58 age-, sex-, and socioeconomic status-matched adults without a lifetime history of major depression. Results: Individuals with a positive history of major depression had significantly lower peak prolactin responses than controls. This finding was not attributable to weight, fenfluramine bioavailability, or baseline prolactin levels. Conclusions: This is the first investigation to compare men and women with a history of depression but not depressed at the time of the fenfluramine challenge to a similar group of healthy controls. The results are consistent with the hypothesis that central serotonergic activity is persistently disturbed in adults who experience depressive episodes.