A fenfluramine-activated FDG-PET study of borderline personality disorder

Background: Impulsive aggression in patients with personality disorders is associated with diminished levels of cerebrospinal fluid (CSF) S-HIAA, blunted neuroendocrine responses to serotonergic agonists, and decreased glucose utilization in the prefrontal cortex. We tested the hypothesis that impulsive aggression in borderline personality disorder (BPD) may lie associated with diminished serotonergic regulation in the prefrontal cortex, using positron-emission tomography (PET) neuroimaging during pharmacologic challenge with d,l fenfluramine (FEN). Methods: A 2-day, single-blind placebo-controlled FEN challenge study was conducted in five patients with BPD land no Axis I MDD) and eight healthy control participants. On Day 1, 4 mCi [F-18]-fluorodeoxyglucose (FDG) was injected 3 hours after ingestion of placebo; on Day 2, FDG was injected 3 hours after ingestion of .8 mg/kg to 60 mg of d,l fenfluramine. After 30 min, a 45-min emission scan was acquired on the Siemans/CTI 951r/31 scanner. PET data were aligned to MR images and analyzed by Statistical Parametric Mapping (SPM96). Results: In response to placebo, uptake of FDG was greater in control participants than patients in large areas of the prefrontal cortex including medial and orbital regions bilaterally IBA 10-11) left superior temporal gyrus, and right insular cortex. There were no areas in which patients had greater relative regional uptake than control participants. In response to FEN, relative regional uptake of FDG (relative to placebo) was greater in central participants compared to patients in medial and orbital regions of right prefrontal cortex (BA 10), left middle and superior temporal gyri (BA 22-23), left parietal lobe IBA 40), and left caudate body. Conclusions: Patients with BPD have diminished response to serotonergic stimulation in areas of prefrontal cortex associated with regulation of impulsive behaviour. (C) 2000 Society of Biological Psychiatry.