Department of Radiology and Biomedical Imaging, Yale University, New Haven, CT, USA.
Department of Psychiatry, Yale University, New Haven, CT, USA.
Neuropsychopharmacology. 2019 Sep;44(10):1714-1719. doi: 10.1038/s41386-019-0379-7. Epub 2019 Mar 30.
Kappa opioid receptors (KORs) have been characterized as an aversive system in the brain and implicated in social behavior in preclinical models. This work investigated the effect of social status on the KOR system in humans using positron emission tomography (PET) imaging with the novel KOR agonist radiotracer [C]EKAP. Eighteen healthy participants (mean age 41.2 ± 9.3) completed the Barratt Simplified Measure of Social Status (BSMSS), an MRI and an [C]EKAP PET scan on the High Resolution Research Tomograph. Arterial blood sampling and metabolite analysis were conducted to obtain the input function. Regions of interest were based upon an MR template and included the reward/aversion areas of the brain. The multilinear analysis-1 (MA1) method was applied to the regional time-activity curves (TACs) to calculate [C]EKAP regional volume of distribution (V). Mixed models and Pearson correlation coefficients were used for body mass index (BMI), gender and age, with age being dropped in subsequent analyses because of nonsignificance. An overall effect of primary ROIs (F 7.43, p < 0.0001), BSMSS score (F 7.45, p = 0.02), BMI (F 23.5, p < 0.001), and gender (F 23.75, p < 0.001), but not age (F 1.12, p = 0.35) was observed. Regional [C]EKAP V and BSMSS were found to be negatively correlated in the amygdala (r = -0.69, p < 0.01), anterior cingulate cortex (r = -0.56, p = 0.02), caudate (r = -0.66, p < 0.01), frontal cortex (r = -0.52, p = 0.04), hippocampus (r = -0.60, p = 0.01), pallidum (r = -0.59, p = 0.02), putamen (r = -0.62, p = 0.01), and ventral striatum (r = -0.66, p < 0.01). In secondary (non-reward) regions, correlations of [C]EKAP V and BSMSS were nonsignificant with the exception of the insula. There was an inverse correlation between social status and KOR levels that was largely specific to the reward/aversion (e.g., saliency) areas of the brain. This finding suggests the KOR system may act as a mediator for the negative effects of social behaviors in humans.
κ 阿片受体（KOR）已被确定为大脑中的一种厌恶系统，并在临床前模型中与社会行为有关。本研究使用新型 KOR 激动剂放射性示踪剂 [C]EKAP 通过正电子发射断层扫描（PET）成像，研究了社会地位对人类 KOR 系统的影响。18 名健康参与者（平均年龄 41.2±9.3）完成了巴雷特简化社会地位量表（BSMSS）、磁共振成像和 [C]EKAP PET 扫描高分辨率研究断层扫描。进行了动脉采血和代谢物分析以获得输入函数。感兴趣的区域基于磁共振模板，包括大脑的奖励/厌恶区域。应用多线性分析-1（MA1）方法对区域时间活动曲线（TAC）进行分析，以计算 [C]EKAP 区域分布容积（V）。混合模型和 Pearson 相关系数用于体重指数（BMI）、性别和年龄，由于不显著，随后的分析中排除了年龄。主要 ROI（F7.43，p<0.0001）、BSMSS 评分（F7.45，p=0.02）、BMI（F23.5，p<0.001）和性别（F23.75，p<0.001）的总体效应，但年龄（F1.12，p=0.35）没有。观察到 [C]EKAP V 和 BSMSS 在杏仁核（r=-0.69，p<0.01）、前扣带皮层（r=-0.56，p=0.02）、尾状核（r=-0.66，p<0.01）、额叶皮层（r=-0.52，p=0.04）、海马体（r=-0.60，p=0.01）、苍白球（r=-0.59，p=0.02）、壳核（r=-0.62，p=0.01）和腹侧纹状体（r=-0.66，p<0.01）之间呈负相关。在次要（非奖励）区域，[C]EKAP V 和 BSMSS 之间的相关性无显著性，除了岛叶。社会地位和 KOR 水平之间存在反比关系，主要局限于大脑的奖励/厌恶（例如，显著性）区域。这一发现表明，KOR 系统可能是人类社会行为负面影响的中介。
