Altered response to intravenous D-fenfluramine during depression using [15O]-PET

The purpose of this study was to compare serotonergic function between healthy and depressed subjects by detecting changes in regional cerebral blood flow after administration of serotonin agonist intravenous d-fenfluramine (IV d-fen). Previous studies have often detected decreased hormone responses in depressed subjects as compared to healthy controls after serotonin agonists. Unfortunately, hormone responses represent the hypothalamic-pituitary axis only and may not represent other brain structures. With [15O] H2O-PET, blood flow to these other brain regions may be detected. Six depressed and 8 healthy subjects all aged 18-30 were given IV d-fen. Each had [15O] H2O-PET scans which were done 25 and 10 minutes before, and 20 and 35 minutes after IV d-fen administration. 60 mCi of radiotracer [15O] H2O was given prior to each scan. During scanning, subjects did a simple visual-motor task. Differences in activations (activation = post IV d-fen scans - pre IV d-fen scans) between depressed and healthy groups were analyzed using statistical parametric mapping. Regions within left inferior parietal and posterior temporal lobe, and right lateral, anterior frontal cortex demonstrated significantly greater activations in healthy controls (p<0.01). Regions of right frontal lobe posteriorly, and right inferior thalamus-midbrain showed significantly greater activations in depressed subjects (p<0.01). These preliminary findings support differences in brain responsivity to IV d-fen between healthy and depressed subjects. They also indicate that these differences are not global and uniform. Instead, the differences in activations are related to particular anatomical localizations.