Herpesviruses and neuropsychiatric disorders: overlooked adversaries or innocent bystanders?
Herpesviruses and neuropsychiatric disorders: overlooked adversaries or innocent bystanders?
复制标题
疱疹病毒和神经精神疾病：被忽视的对手还是无辜的旁观者？
DOI：
10.1038/s41386-023-01674-5
复制
发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Savitz,Jonathan
中科院分区：
文献类型：
--
作者：
Zheng,Haixia;Savitz,Jonathan
神经营养性疱疹病毒与神经和精神疾病有关已有50多年的历史，但这些常见病毒可导致大脑和精神疾病的想法传统上一直受到怀疑。在神经病学的某些领域，这种情况可能正在改变。基于先前的流行病学研究，Bjornevik等人在《科学》杂志上报告称，EB病毒（EBV）感染后多发性硬化症（MS）的风险增加了32倍，神经丝轻链（神经变性的生物标志物）的浓度仅在EBV血清转换后增加[1]。在发现/确认设计中使用纵向FinnGen和横截面UK Biobank数据集，Levine等人能够检测22种不同病毒暴露与各种神经退行性疾病之间的可复制关联，包括EBV-MS关联的复制[2]。此外，在FinnGen数据集中，阿尔茨海默病（AD）与AD诊断前1-5年的单纯疱疹病毒1（HSV-1）感染相关，表明存在因果关系。我们的研究小组专注于巨细胞病毒（CMV），这是一种β疱疹病毒，可在脑和免疫细胞中建立终身潜伏感染，并已知会在免疫抑制人群中引起神经系统疾病。我们最近评估了CMV血清状态对最近遭受脑震荡的足球运动员和匹配的未受伤运动员的白色物质微观结构和皮质厚度的影响[3]。在未受伤的运动员中没有观察到CMV效应。然而，在对7种潜在混淆进行倾向性匹配后，与CMV阴性运动员相比，CMV阳性运动员在脑震荡后表现出更大的轴向和径向峰度以及皮质厚度减少。峰度增加被认为反映了轴突内碎片或细胞结构的增加，神经炎症是其中一个潜在的解释。我们假设与脑损伤相关的神经炎症促使CMV重新激活，进而导致组织损伤和宿主抗病毒免疫反应，从而放大炎症[3]。同样，我们假设CMV可能作为精神疾病的病理辅助因子，类似于火灾的助燃剂。在过去的2年中，我们发表了大量证据表明，在重度抑郁症患者中，CMV感染与脑异常（灰质体积减少、白色物质微结构改变和相关的连接不足）之间存在相关性（例如，[4]）。此外，我们最近发现，CMV阳性的尸检样本，
Neurotrophic herpesviruses have been linked with neurological and psychiatric disorders for more than 50 years but the idea that these common viruses can cause diseases of brain and mind has traditionally been viewed with skepticism. In some areas of neurology this may be changing. Building on prior epidemiological studies, Bjornevik et al. reported in Science that the risk for multiple sclerosis (MS) was increased 32-fold after infection by Epstein-Barr virus (EBV) and that concentrations of neurofilament light chain, a biomarker of neurodegeneration, were increased only after EBV seroconversion [1]. Using the longitudinal FinnGen and cross-sectional UK Biobank datasets in a discovery/confirmation design, Levine et al. were able to detect replicable associations between 22 different viral exposures and various classes of neurodegenerative diseases including a replication of the EBV-MS association [2]. Further, in the FinnGen dataset, Alzheimer’s disease (AD) was associated with a herpes simplex virus 1 (HSV-1) infection 1–5 years prior to AD diagnosis suggesting a causal relationship. Our group has focused on cytomegalovirus (CMV), a beta herpesvirus that establishes life-long, latent infections in brain and immune cells and is known to cause neurological disease in immunosuppressed populations. We recently evaluated the effect of CMV serostatus on white matter microstructure and cortical thickness in football players who had sustained a recent concussion and matched uninjured athletes [3]. No CMV effect was observed in the uninjured athletes. However, after propensitymatching for seven potential confounds, CMV positive athletes showed greater axial and radial kurtosis as well as reduced cortical thickness in the aftermath of concussion compared with CMV negative athletes with concussion. Increased kurtosis is thought to reflect increased intra-axonal debris or cellularity of which neuroinflammation is one potential explanation. We hypothesize that the neuroinflammation associated with brain injury is precipitating the reactivation of CMV which is in turn contributing to tissue damage and host anti-viral immune responses, thereby amplifying inflammation [3].Similarly, we have hypothesized that CMV may act as a pathological co-factor in psychiatric disorders akin to an accelerant on a fire. In the past 2 years, we have published extensive evidence of an association between CMV infection and brain abnormalities (reduced gray matter volume, white matter microstructural alterations and associated hypoconnectivity) in individuals with major depressive disorder (eg,[4]). Moreover, we have recently found that CMV positive postmortem samples from