Witte A Veronica, Flöel Agnes, Stein Patrycja, Savli Markus, Mien Leonhard-Key, Wadsak Wolfgang, Spindelegger Christoph, Moser Ulrike, Fink Martin, Hahn Andreas, Mitterhauser Markus, Kletter Kurt, Kasper Siegfried, Lanzenberger Rupert
Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.
Hum Brain Mapp. 2009 Aug;30(8):2558-70. doi: 10.1002/hbm.20687.
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.
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.
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).
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.
多项研究表明，血清素调节冲动性及对攻击行为的抑制控制。众所周知，攻击行为也会受到性激素的影响，而性激素会对血清素能神经传递产生作用。本研究旨在阐明人类攻击行为、抑制性血清素能5-HT(1A)受体和性激素之间的潜在相互作用。
33名健康志愿者（16名女性，年龄26.24±5.5岁）完成了一份经过验证的包含攻击行为五个维度的问卷。随后，所有受试者接受了用放射性配体[羰基-(11)C]WAY-100635进行的正电子发射断层扫描，以量化前额叶皮质、边缘区域和中脑中的5-HT(1A)结合潜能（BP(ND)）。此外，还测量了睾酮、17β-雌二醇和性激素结合球蛋白（SHBG）的血浆水平。使用相关性分析、多变量方差分析和线性回归分析了攻击行为评分、区域5-HT(1A) BP(ND)和激素水平之间的关系。
统计分析显示，在前额叶皮质（所有P<0.041）和前扣带回皮质（P = 0.016）中，攻击行为评分较高的受试者的5-HT(1A)受体BP(ND)更高。攻击性更强的受试者的SHBG水平也更低（P = 0.015）。此外，较高的SHBG水平与额叶（P = 0.048）和扣带回皮质（所有P<0.013）以及杏仁核（P = 0.03）中较低的5-HT(1A) BP(ND)相关。
本研究首次为人类5-HT(1A)受体分布、性激素和攻击行为之间的特定相互关系提供了证据。我们的研究结果表明，在攻击性更强的受试者中，由于额叶5-HT(1A)受体数量增加或活性增强，导致下游控制减弱，这可能受到性激素的调节。
