Kappa opioid receptor binding in major depression: A pilot study
Kappa opioid receptor binding in major depression: A pilot study
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DOI：
10.1002/syn.22042
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发表时间：
2018-09-01
期刊：
影响因子：
2.3
通讯作者：
Mann, J. John
中科院分区：
文献类型：
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作者：
Miller, Jeffrey M.;Zanderigo, Francesca;Mann, J. John
在动物模型中，内源性阿片介导应激的病理反应。然而，kappa阿片受体（KOR）与人类生活压力和精神病理的关系尚未得到很好的描述。这项初步研究首次使用正电子发射断层扫描（PET）来量化人体内重度抑郁症（MDD）的KOR。在13名健康志愿者和10名患有MDD的参与者中，使用[C-11]GR103545放射性示踪剂通过PET成像来定量体内KOR结合。我们研究了区域[C-11]GR103545总分布体积（V-T）与诊断、童年创伤、近期生活压力，以及在改进的特里尔社会压力测试（mTSST）、杏仁核、海马、腹侧纹状体和中缝核期间唾液皮质醇水平的亚样本之间的关系。还进行了全脑体素分析。[C-11]GR103545 V-T在四个先验roi上在重度抑郁症参与者和健康志愿者之间无显著差异（p = 0.50）。[C-11]GR103545 V-T与报告的童年逆境（p = 0.17）或最近的生活压力（p = 0.56）无关。在mTSST期间，[C-11]GR103545 V-T与皮质醇曲线下相对于地面的面积呈趋势水平负相关（p = 0.081）。全脑体素对比不显著。区域[C-11]GR103545 V-T是体内KOR结合的一种测量方法，在该试点样本中不能区分MDD和健康志愿者。未来的研究可能会在KOR异常风险增加的抑郁个体亚组中检查KOR结合，包括共同发生的情绪和物质使用障碍，以及伴有精神病性特征的抑郁。
Endogenous kappa opioids mediate pathological responses to stress in animal models. However, the relationship of the kappa opioid receptor (KOR) to life stress and to psychopathology in humans is not well described. This pilot study sought, for the first time, to quantify KOR in major depressive disorder (MDD) in vivo in humans using positron emission tomography (PET). KOR binding was quantified in vivo by PET imaging with the [C-11]GR103545 radiotracer in 13 healthy volunteers and 10 participants with current MDD. We examined the relationship between regional [C-11]GR103545 total volume of distribution (V-T) and diagnosis, childhood trauma, recent life stress, and, in a subsample, salivary cortisol levels during a modified Trier Social Stress Test (mTSST), amygdala, hippocampus, ventral striatum and raphe nuclei. Whole-brain voxel-wise analyses were also performed. [C-11]GR103545 V-T did not differ significantly between MDD participants and healthy volunteers in the four a priori ROIs (p = 0.50). [C-11]GR103545 V-T was unrelated to reported childhood adversity (p = 0.17) or recent life stress (p = 0.56). A trend-level inverse correlation was observed between [C-11]GR103545 V-T and cortisol area-under-the curve with respect to ground during the mTSST (p = 0.081). No whole-brain voxel-wise contrasts were significant. Regional [C-11]GR103545 V-T, a measure of in vivo KOR binding, does not differentiate MDD from healthy volunteers in this pilot sample. Future studies may examine KOR binding in subgroups of depressed individuals at increased risk for KOR abnormalities, including co-occurring mood and substance use disorders, as well as depression with psychotic features.