title: Serotonin transporter availability in impulsive aggressive personality disordered patients: a PET study with [11C]DASB.
abstract: Serotonin (5-HT) has consistently been implicated in the pathophysiology of impulsive aggression. In the current study, we tested the hypothesis that 5-HT transporter (5-HTT) binding is reduced in the anterior cingulate cortex (ACC) in impulsive aggressive patients. Additionally, we characterized pathological personality dimensions, with a specific focus on callousness (i.e. emotional indifference, a facet of psychopathy). Callousness is putatively positively correlated with presynaptic 5-HT, and thus could potentially confound the hypothesized negative relation between 5-HTT levels and trait aggression. We determined 5-HTT binding with positron emission tomography and [(11)C]DASB in 29 patients with intermittent explosive disorder (IED-IR) and 30 controls. We assessed group differences in 5-HTT binding in the pregenual ACC, amygdala and subcortical regions and examined correlations between 5-HTT binding and clinical measures. There were no significant differences in 5-HTT binding between IED-IR patients and controls. Trait callousness exhibited a significant, positive correlation with ACC 5-HTT availability. Among IED-IR patients, a trend-level negative partial correlation was observed between trait aggression and ACC 5-HTT availability, while covarying for callousness and age. Exploratory analyses revealed a significant negative correlation between state aggression levels and 5-HTT availability in subcortical regions, namely striatum and thalamus. We did not confirm our hypothesis of lower ACC 5-HTT availability in impulsive aggressive patients, however, the positive correlation between callousness and ACC 5-HTT availability likely played a confounding role. Subtypes of aggression (e.g., reactive vs. proactive aggression), which are differentially associated with pathological personality dimensions such as callousness, may contribute to variability between 5-HT functioning and aggression.
authors.affiliation: Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, USA; New York State Psychiatric Institute, New York, USA.
authors.forename: Elsmarieke
authors.initials: E
authors.lastname: van de Giessen
authors.affiliation: James J. Peters Department of Veterans Affairs Medical Center, Bronx, New York, USA; Department of Psychiatry, Mount Sinai School of Medicine, New York, USA.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Rosell
authors.affiliation: Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, USA; New York State Psychiatric Institute, New York, USA.
authors.forename: Judy L
authors.initials: JL
authors.lastname: Thompson
authors.affiliation: Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, USA; New York State Psychiatric Institute, New York, USA.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, USA; New York State Psychiatric Institute, New York, USA.
authors.forename: Ragy R
authors.initials: RR
authors.lastname: Girgis
authors.affiliation: James J. Peters Department of Veterans Affairs Medical Center, Bronx, New York, USA; Department of Psychiatry, Mount Sinai School of Medicine, New York, USA.
authors.forename: Yosefa
authors.initials: Y
authors.lastname: Ehrlich
authors.affiliation: Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, USA; New York State Psychiatric Institute, New York, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Slifstein
authors.affiliation: Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, USA; New York State Psychiatric Institute, New York, USA.
authors.forename: Anissa
authors.initials: A
authors.lastname: Abi-Dargham
authors.affiliation: James J. Peters Department of Veterans Affairs Medical Center, Bronx, New York, USA; Department of Psychiatry, Mount Sinai School of Medicine, New York, USA. Electronic address: larry.siever@va.gov.
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Siever
mesh_terms: D000328:Adult; D000374:Aggression; D000704:Analysis of Variance; D000814:Aniline Compounds; D001921:Brain / Q000000981:diagnostic imaging* / Q000473:pathology; D003193:Compulsive Personality Disorder / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D013223:Statistics as Topic; D013440:Sulfides
chemical_list: C412822:3-amino-4-(2-dimethylaminomethylphenylsulfanyl)benzonitrile; D000814:Aniline Compounds; D050486:Serotonin Plasma Membrane Transport Proteins; D013440:Sulfides
keywords: Anterior cingulate cortex; Callousness; Impulsive aggression; Intermittent explosive disorder; Positron emission tomography; Serotonin transporter