title: Pre- and postsynaptic serotonergic differences in males with extreme levels of impulsive aggression without callous unemotional traits: a positron emission tomography study using (11)C-DASB and (11)C-MDL100907.
abstract: BACKGROUND
  Impulsive aggression (IA) in adults is associated with brain serotonin (5-HT) system abnormalities and is more common following childhood adversity. Within aggressive behavior, IA and callous unemotional (CU) traits are core components of differentiable factors with opposing 5-HT abnormalities. We aimed to investigate 5-HT abnormalities in IA and potential correlations with severity of childhood adversity while controlling for confounding 5-HT effects of high CU traits and mental disorders.
  
  
  METHODS
  Healthy male subjects (mean age 34 ± 9 years) without high CU traits were recruited with IA ratings in the high (n = 14) and low (n = 13) population extremes. Serotonin transporter (SERT) and 5-HT(2A) receptor availability was measured in multiple brain regions using positron emission tomography with (11)C-DASB and (11)C-MDL100907, respectively, and compared between high-IA and low-IA groups. Correlations were measured between SERT and 5-HT(2A) receptor availability, impulsivity and aggression, and childhood adversity.
  
  
  RESULTS
  Compared with the low-IA group, SERT were significantly higher in brainstem regions in the high-IA group (by 29.0% ± 11.4%) and modestly lower across cortical regions (by 11.1% ± 6.0%), whereas 5-HT(2A) receptors were also modestly lower (by 8.6% ± 4.0%). Across all subjects, brainstem SERT were significantly positively correlated with impulsivity, aggression, and childhood trauma ratings. Within the high-IA group, higher brainstem SERT was most strongly predicted by severity of childhood trauma (r = .76 in midbrain).
  
  
  CONCLUSIONS
  Pre-and postsynaptic 5-HT differences are present in men with high levels of IA and are strongly suggestive of a persisting effect of childhood adversity on serotonergic neurodevelopment and emotional-behavioral control.
authors: Mental Health and Neurodegeneration Research Group, Wolfson Molecular Imaging Centre, University of Manchester, Manchester, UK.
authors: Angela J
authors: AJ
authors: Rylands
authors: Rainer
authors: R
authors: Hinz
authors: Matthew
authors: M
authors: Jones
authors: Sophie E
authors: SE
authors: Holmes
authors: Maria
authors: M
authors: Feldmann
authors: Gavin
authors: G
authors: Brown
authors: Adam W
authors: AW
authors: McMahon
authors: Peter S
authors: PS
authors: Talbot
mesh_terms: D000328:Adult; D000374:Aggression / Q000502:physiology* / Q000523:psychology*; D000814:Aniline Compounds; D002648:Child; D002649:Child Abuse / Q000523:psychology; D004644:Emotions / Q000502:physiology; D005464:Fluorobenzenes; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007175:Impulsive Behavior / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000523:psychology*; D007361:Intelligence Tests; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010880:Piperidines; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism / Q000502:physiology*; D012702:Serotonin Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D013440:Sulfides; D013569:Synapses / Q000000981:diagnostic imaging* / Q000502:physiology*; D055815:Young Adult
chemical_list: C412822:3-amino-4-(2-dimethylaminomethylphenylsulfanyl)benzonitrile; D000814:Aniline Compounds; D005464:Fluorobenzenes; D010880:Piperidines; D019275:Radiopharmaceuticals; D044402:Receptor, Serotonin, 5-HT2A; D012702:Serotonin Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins; D013440:Sulfides; D012701:Serotonin; C079049:volinanserin