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, blun ted neuroendocrine responses to serotonergic agonists, and decreased glucos e utilization in the prefrontal cortex. We tested the hypothesis that impul sive aggression in borderline personality disorder (BPD) may lie associated with diminished serotonergic regulation in the prefrontal cortex, using po sitron-emission tomography (PET) neuroimaging during pharmacologic challeng e with d,l fenfluramine (FEN). Methods: A 2-day, single-blind placebo-controlled FEN challenge study was c onducted in five patients with BPD land no Axis I MDD) and eight healthy co ntrol participants. On Day 1, 4 mCi [F-18]-fluorodeoxyglucose (FDG) was inj ected 3 hours after ingestion of placebo; on Day 2, FDG was injected 3 hour s 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 Mappi ng (SPM96). Results: In response to placebo, uptake of FDG was greater in control parti cipants than patients in large areas of the prefrontal cortex including med ial and orbital regions bilaterally IBA 10-11) left superior temporal gyrus , and right insular cortex. There were no areas in which patients had great er relative regional uptake than control participants. In response to FEN, relative regional uptake of FDG (relative to placebo) was greater in centra l 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 sti mulation in areas of prefrontal cortex associated with regulation of impuls ive behaviour. (C) 2000 Society of Biological Psychiatry.