Cytomegalovirus antibodies are associated with mood disorders, suicide, markers of neuroinflammation, and microglia activation in postmortem brain samples.
Cytomegalovirus antibodies are associated with mood disorders, suicide, markers of neuroinflammation, and microglia activation in postmortem brain samples.
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巨细胞病毒抗体与死后大脑样本中的情绪障碍、自杀、神经炎症标志物和小胶质细胞激活有关。
DOI：
10.1038/s41380-023-02162-4
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发表时间：
2023
影响因子：
11
通讯作者：
Savitz,Jonathan
中科院分区：
文献类型：
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作者：
Zheng,Haixia;Webster,MareeJ;Weickert,CynthiaShannon;Beasley,ClareL;Paulus,MartinP;Yolken,RobertH;Savitz,Jonathan
巨细胞病毒（CMV）是一种常见的神经营养性疱疹病毒，可被炎症重新激活并引起中枢神经系统疾病。我们假设巨细胞病毒可能通过(1)通过诱导抗病毒免疫反应加剧炎症，(2)将外周炎症转化为神经炎症，从而导致某些精神疾病的神经炎症。我们研究了血液中抗巨细胞病毒抗体的存在是否与死后样本中精神疾病、自杀、神经炎症和背外侧前额叶皮层（DLPFC）中的小胶质细胞密度有关。资料（114例精神分裂症患者；78例双相情感障碍患者；87例抑郁症患者；85例对照）来自斯坦利医学研究所。基于使用四种炎症相关基因表达数据的递归两步聚类分析，来自82个样本子集的DLPFC基因表达数据被分为“高”（n=30）和“低”（n=52）炎症组。测量非分支与分支小胶质细胞的比例，小胶质细胞激活的代理，可用于49个样本的子集。所有的分析都控制了年龄、性别、种族、死后时间、pH值对基因表达和小胶质细胞结果的影响。巨细胞病毒血清阳性显著增加了情绪障碍诊断的几率（双相情感障碍：OR = 2.45；重度抑郁症：OR = 3.70），在精神病学样本中，自杀的几率（OR = 2.09）。抗巨细胞病毒抗体滴度较高的样本更有可能是“高”炎症组的成员（OR = 4.41，由精神分裂症和双相情感障碍样本驱动）。CMV阳性样本也显示DLPFC第一层非分枝小胶质细胞与分枝小胶质细胞的比例增加（Cohen’s d = 0.81），而DLPFC整体的这一比例无显著增加（d = 0.56）。研究结果提出了CMV再激活导致神经炎症的可能性，而神经炎症是某些精神疾病的基础。
Cytomegalovirus (CMV) is a common, neurotrophic herpesvirus that can be reactivated by inflammation and cause central nervous system disease. We hypothesize that CMV may contribute to the neuroinflammation that underlies some psychiatric disorders by (1) exacerbating inflammation through the induction of anti-viral immune responses, and (2) translating peripheral inflammation into neuroinflammation. We investigated whether the presence of anti-CMV antibodies in blood were associated with mental illness, suicide, neuroinflammation, and microglial density in the dorsolateral prefrontal cortex (DLPFC) in postmortem samples. Data (n=114 with schizophrenia;n=78 with bipolar disorder;n=87 with depression;n=85 controls) were obtained from the Stanley Medical Research Institute. DLPFC gene expression data from a subset of 82 samples were categorized into “high” (n=30), and “low” (n=52) inflammation groups based on a recursive two-step cluster analysis using expression data for four inflammation-related genes. Measurements of the ratio of non-ramified to ramified microglia, a proxy of microglial activation, were available for a subset of 49 samples. All analyses controlled for age, sex, and ethnicity, as well as postmortem interval, and pH for gene expression and microglial outcomes. CMV seropositivity significantly increased the odds of a mood disorder diagnosis (bipolar disorder: OR = 2.45; major depression: OR = 3.70) and among the psychiatric samples, of suicide (OR = 2.09). Samples in the upper tercile of anti-CMV antibody titers were more likely to be members of the “high” inflammation group (OR = 4.41, an effect driven by schizophrenia and bipolar disorder samples). CMV positive samples also showed an increased ratio of non-ramified to ramified microglia in layer I of the DLPFC (Cohen’s d = 0.81) as well as a non-significant increase in this ratio for the DLPFC as a whole (d = 0.56). The results raise the possibility that the reactivation of CMV contributes to the neuroinflammation that underlies some cases of psychiatric disorders.