No effect of depression on [15O]H2O PET response to intravenous d-fenfluramine

Objective: Subnormal prolactin responses to the serotonin-releasing agonist fenfluramine occur in depression. Since many measures of serotonin pathology occur in depression, abnormal responses to fenfluramine may occur in brain structures other than the hypothalamic-pituitary axis. One study compared six depressed and six healthy subjects' responses to oral d,l-fenfluramine by assessing [F-18]fluorodeoxyglucose uptake as detected by positron emission tomography (PET), That study showed several abnormalities within the cortex, and the authors concluded that low responsivity to d,l-fenfluramine is widespread in depression. In this study abnormalities in regional neuromodulation by serotonin in major depression were assessed with intravenous d-fenfluramine and [O-15]H2O PET. Method: Changes in regional cerebral blood flow (CBF) were detected by using [O-15]H2O PET after administration of intravenous d-fenfluramine to 13 depressed and 18 healthy women. The PET scans were done 20 and 5 minutes before and 20 and 35 minutes after d-fenfluramine administration. Differences between the depressed and healthy groups in change in regional CBF (mean postfenfluramine minus mean prefenfluramine) were analyzed by using statistical parametric mapping. Results: There were no significant differences between depressed and healthy subjects; in fact, changes in regional CBF after intravenous d-fenfluramine were remarkably similar. Conclusions: Degrees of neuronal responsivity to d-fenfluramine are similar in depressed and healthy subjects. Differences between the previous and current findings may be accounted for by greater specificity of intravenous d-fenfluramine to serotonin release, timing of scans, paucity of suicidal subjects in the current study, or greater variance in regional CBF from direct vascular effects of serotonin.