No effect of depression on [(15)O]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 [18F]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 [(15)O]H2O PET. METHOD Changes in regional cerebral blood flow (CBF) were detected by using [(15)O]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.