van de Giessen Elsmarieke, Rosell Daniel R, Thompson Judy L, Xu Xiaoyan, Girgis Ragy R, Ehrlich Yosefa, Slifstein Mark, Abi-Dargham Anissa, Siever Larry J
Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, USA; New York State Psychiatric Institute, New York, USA.
James J. Peters Department of Veterans Affairs Medical Center, Bronx, New York, USA; Department of Psychiatry, Mount Sinai School of Medicine, New York, USA.
J Psychiatr Res. 2014 Nov;58:147-54. doi: 10.1016/j.jpsychires.2014.07.025. Epub 2014 Aug 6.
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.
血清素（5-羟色胺，5-HT）一直被认为与冲动性攻击行为的病理生理学有关。在本研究中，我们检验了这样一个假设：冲动性攻击行为患者前扣带回皮质（ACC）中的5-羟色胺转运体（5-HTT）结合减少。此外，我们对病理性人格维度进行了特征描述，特别关注了冷酷无情（即情感冷漠，精神病态的一个方面）。冷酷无情被认为与突触前5-羟色胺呈正相关，因此可能会混淆5-HTT水平与特质攻击性之间假设的负相关关系。我们使用正电子发射断层扫描和[(11)C]DASB测定了29例间歇性爆发障碍患者（IED-IR）和30名对照者的5-HTT结合情况。我们评估了前膝部ACC、杏仁核和皮质下区域5-HTT结合的组间差异，并检查了5-HTT结合与临床指标之间的相关性。IED-IR患者与对照者之间的5-HTT结合没有显著差异。特质冷酷无情与ACC的5-HTT可用性呈显著正相关。在IED-IR患者中，在控制了冷酷无情和年龄后，观察到特质攻击性与ACC的5-HTT可用性之间存在趋势水平的负偏相关。探索性分析显示，状态攻击性水平与皮质下区域（即纹状体和丘脑）的5-HTT可用性之间存在显著负相关。我们没有证实冲动性攻击行为患者ACC的5-HTT可用性较低这一假设，然而，冷酷无情与ACC的5-HTT可用性之间的正相关可能起到了混淆作用。攻击行为的亚型（例如，反应性攻击与主动性攻击）与冷酷无情等病理性人格维度有不同的关联，可能导致5-羟色胺功能与攻击行为之间的变异性。
