The Neuroimmune and Neurotoxic Fingerprint of Major Neurocognitive Psychosis or Deficit Schizophrenia: a Supervised Machine Learning Study
The Neuroimmune and Neurotoxic Fingerprint of Major Neurocognitive Psychosis or Deficit Schizophrenia: a Supervised Machine Learning Study
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DOI：
10.1007/s12640-019-00112-z
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发表时间：
2020-03-01
影响因子：
3.7
通讯作者：
Maes, Michael
中科院分区：
文献类型：
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作者：
Al-Hakeim, Hussein Kadhem;Almulla, Abbas F.;Maes, Michael
目前还没有研究使用M1巨噬细胞细胞因子联合趋化因子如CCL2和CCL11检测重性神经认知精神病（MNP）或缺乏性精神分裂症的免疫指纹。本研究通过分析血浆IL-1 β、sIL-1RA、TNF α、sTNFR1、sTNFR2、CCL2和CCL11在120名MNP和54名健康对照中与神经认知评分（用精神分裂症认知简要评估）和PHEMN（精神病性、敌意、兴奋、行为举止和阴性）症状相关的水平，描绘了MNP的神经免疫指纹。用CCL11、TNF α、IL-1 β和sIL-1RA的组合预测MNP效果最好，在接受者工作曲线下的自适应（n = 2000）面积为0.985。反映M1巨噬细胞活性和神经毒性潜能的综合评分，包括CCL11和CCL2的影响，在MNP中显著升高。PHEM（38.4-52.6%）和阴性（65.8-74.4%）症状的很大一部分差异可以用免疫标记物的组合来解释，其中CCL11是最重要的。同样的标记解释了迷你精神状态测试、列表学习、数字排序任务、类别实例、受控单词联想、符号编码和伦敦塔的大部分差异。偏最小二乘分析显示，精神分裂症总体严重程度的72.7%的方差可以用IL-1 β、sIL-1RA、CCL11、TNF α和教育程度的回归来解释。综上所述，上述标志物的结合将MNP定义为一种独特的神经免疫疾病，免疫神经毒性的增加也决定了记忆和执行障碍以及PHEMN症状。
No studies have examined the immune fingerprint of major neurocognitive psychosis (MNP) or deficit schizophrenia using M1 macrophage cytokines in combination with chemokines such as CCL2 and CCL11. The present study delineated the neuroimmune fingerprint of MNP by analyzing plasma levels of IL-1 beta, sIL-1RA, TNF alpha, sTNFR1, sTNFR2, CCL2, and CCL11 in 120 MNP versus 54 healthy controls in association with neurocognitive scores (as assessed with the Brief Assessment of Cognition in Schizophrenia) and PHEMN (psychotic, hostility, excitation, mannerism and negative) symptoms. MNP was best predicted by a combination of CCL11, TNF alpha, IL-1 beta, and sIL-1RA which yielded a bootstrapped (n = 2000) area under the receiver operating curve of 0.985. Composite scores reflecting M1 macrophage activity and neurotoxic potential including effects of CCL11 and CCL2 were significantly increased in MNP. A large part of the variance in PHEM (38.4-52.6%) and negative (65.8-74.4%) symptoms were explained by combinations of immune markers whereby CCL11 was the most important. The same markers explained a large part of the variance in the Mini-Mental State examination, list learning, digit sequencing task, category instances, controlled word association, symbol coding, and Tower of London. Partial least squares analysis showed that 72.7% of the variance in overall severity of schizophrenia was explained by the regression on IL-1 beta, sIL-1RA, CCL11, TNF alpha, and education. It is concluded that the combination of the abovementioned markers defines MNP as a distinct neuroimmune disorder and that increased immune neurotoxicity determines memory and executive impairments and PHEMN symptoms as well.