title: Positron emission tomography of regional brain metabolic responses to a serotonergic challenge in major depressive disorder with and without borderline personality disorder.
abstract: Previous neuroimaging studies of major depression have not controlled for the presence of personality disorders characterized by impulsive aggressive behavior, such as borderline personality disorder (BPD). Using positron emission tomography (PET), we studied regional glucose uptake in response to fenfluramine (FEN) in depressed subjects with BPD (n=11) and depressed patients without Cluster B Axis II disorders (n=8). Subjects were scanned while medication-free after a single blind placebo administration and after FEN on a second day. Brain responses were measured by PET imaging of [18F]fluorodeoxyglucose (FDG) and serial prolactin levels. Scans were compared at a voxel level using statistical parametric mapping. Correlations of changes in relative regional cerebral uptake (rCMRglu) with clinical measures were assessed. Depressed borderline patients had greater relative activity in parietotemporal cortical regions (BA 40, BA 22, and BA 42) before and after FEN activation compared to those without BPD. They also had less relative uptake in the anterior cingulate cortex (BA 32) at baseline compared to depressed patients without BPD and FEN abolished this difference. Impulsivity was positively correlated with rCMRglu in superior and middle frontal cortex (BA 6 and 44). Hostility was positively correlated with rCMRglu in temporal cortical regions (BA 21 and 22). In conclusions, borderline pathology in the context of a Major Depressive Disorder is associated with altered activity in parietotemporal and anterior cingulate cortical regions. Controlling for the presence of BPD in future imaging studies of mood disorders may elucidate similarities and differences in regional serotonergic function in these two often comorbid disorders.
authors.affiliation: Department of Psychiatry, Columbia University, College of Physicians & Surgeons, New York, NY, USA. moquendo@neuron.cpmc.columbia.edu
authors.forename: Maria A
authors.initials: MA
authors.lastname: Oquendo
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Krunic
authors.forename: Ramin V
authors.initials: RV
authors.lastname: Parsey
authors.forename: Matthew
authors.initials: M
authors.lastname: Milak
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Malone
authors.forename: Amy
authors.initials: A
authors.lastname: Anderson
authors.forename: Ronald L
authors.initials: RL
authors.lastname: van Heertum
authors.forename: J
authors.initials: J
authors.lastname: John Mann
mesh_terms: D000328:Adult; D000374:Aggression / Q000523:psychology; D001883:Borderline Personality Disorder / Q000150:complications / Q000378:metabolism* / Q000523:psychology; D001923:Brain Chemistry / Q000187:drug effects*; D002540:Cerebral Cortex / Q000378:metabolism; D003865:Major Depressive Disorder / Q000150:complications / Q000378:metabolism* / Q000523:psychology; D005260:Female; D005277:Fenfluramine / Q000494:pharmacology; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism; D006791:Hostility; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007175:Impulsive Behavior / Q000523:psychology; D049268:Positron-Emission Tomography; D011569:Psychiatric Status Rating Scales; D019275:Radiopharmaceuticals; D012701:Serotonin / Q000378:metabolism; D018490:Serotonin Agents / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology
chemical_list: D005277:Fenfluramine; D019788:Fluorodeoxyglucose F18; D005947:Glucose; D019275:Radiopharmaceuticals; D012701:Serotonin; D018490:Serotonin Agents; D017367:Selective Serotonin Reuptake Inhibitors