title: Aggression is related to frontal serotonin-1A receptor distribution as revealed by PET in healthy subjects.
abstract: OBJECTIVE
  Various studies indicate that serotonin regulates impulsivity and the inhibitory control of aggression. Aggression is also known to be modified by sex hormones, which exert influence on serotonergic neurotransmission. The present study aimed to elucidate potential interactions between human aggression, the inhibitory serotonergic 5-HT(1A) receptor, and sex hormones.
  
  
  METHODS
  Thirty-three healthy volunteers (16 women, aged 26.24 +/- 5.5 yr) completed a validated questionnaire incorporating five dimensions of aggression. Subsequently, all subjects underwent positron emission tomography with the radioligand [carbonyl-(11)C]WAY-100635 to quantify 5-HT(1A) binding potentials (BP(ND)s) in the prefrontal cortex, limbic areas, and midbrain. Also, plasma levels of testosterone, 17beta-estradiol and sex hormone-binding globulin (SHBG) were measured. Relations between aggression scores, regional 5-HT(1A) BP(ND)s, and hormone levels were analyzed using correlations, multivariate analyses of variance, and linear regressions.
  
  
  RESULTS
  Statistical analyses revealed higher 5-HT(1A) receptor BP(ND)s in subjects exhibiting higher aggression scores in prefrontal (all P < 0.041) and anterior cingulate cortices (P = 0.016). More aggressive subjects were also characterized by lower SHBG levels (P = 0.015). Moreover, higher SHBG levels were associated with lower 5-HT(1A) BP(ND)s in frontal (P = 0.048) and cingulate cortices (all P < 0.013) and in the amygdala (P = 0.03).
  
  
  CONCLUSIONS
  The present study provides first-time evidence for a specific interrelation between the 5-HT(1A) receptor distribution, sex hormones, and aggression in humans. Our findings point to a reduced down-stream control due to higher amounts or activities of frontal 5-HT(1A) receptors in more aggressive subjects, which is presumably modulated by sex hormones.
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.
authors.forename: A Veronica
authors.initials: AV
authors.lastname: Witte
authors.forename: Agnes
authors.initials: A
authors.lastname: Flöel
authors.forename: Patrycja
authors.initials: P
authors.lastname: Stein
authors.forename: Markus
authors.initials: M
authors.lastname: Savli
authors.forename: Leonhard-Key
authors.initials: LK
authors.lastname: Mien
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wadsak
authors.forename: Christoph
authors.initials: C
authors.lastname: Spindelegger
authors.forename: Ulrike
authors.initials: U
authors.lastname: Moser
authors.forename: Martin
authors.initials: M
authors.lastname: Fink
authors.forename: Andreas
authors.initials: A
authors.lastname: Hahn
authors.forename: Markus
authors.initials: M
authors.lastname: Mitterhauser
authors.forename: Kurt
authors.initials: K
authors.lastname: Kletter
authors.forename: Siegfried
authors.initials: S
authors.lastname: Kasper
authors.forename: Rupert
authors.initials: R
authors.lastname: Lanzenberger
mesh_terms: D000328:Adult; D000374:Aggression / Q000502:physiology*; D001921:Brain / Q000000981:diagnostic imaging / Q000502:physiology*; D001931:Brain Mapping; D002250:Carbon Radioisotopes; D004958:Estradiol / Q000097:blood; D005260:Female; D006801:Humans; D007700:Kinetics; D008279:Magnetic Resonance Imaging; D008297:Male; D010552:Personality Assessment; D010879:Piperazines; D049268:Positron-Emission Tomography; D011725:Pyridines; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D011795:Surveys and Questionnaires; D013739:Testosterone / Q000097:blood
chemical_list: D002250:Carbon Radioisotopes; D010879:Piperazines; D011725:Pyridines; D012738:Sex Hormone-Binding Globulin; D044282:Receptor, Serotonin, 5-HT1A; D013739:Testosterone; D004958:Estradiol; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide