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Keywords:

  • positron emission tomography;
  • serotonergic 1A receptor;
  • serotonin;
  • aggression;
  • sex hormones;
  • prefrontal cortex

Abstract

Objectives: 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-HT1A receptor, and sex hormones. Experimental Design: 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-11C]WAY-100635 to quantify 5-HT1A binding potentials (BPNDs) in the prefrontal cortex, limbic areas, and midbrain. Also, plasma levels of testosterone, 17ß-estradiol and sex hormone-binding globulin (SHBG) were measured. Relations between aggression scores, regional 5-HT1A BPNDs, and hormone levels were analyzed using correlations, multivariate analyses of variance, and linear regressions. Principal Observations: Statistical analyses revealed higher 5-HT1A receptor BPNDs 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-HT1A BPNDs 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-HT1A 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-HT1A receptors in more aggressive subjects, which is presumably modulated by sex hormones. Hum Brain Mapp 30:2558–2570, 2009. © 2008 Wiley-Liss, Inc.