Webster Maree J, Balagopal Ashwin, Quinn Jeffrey, Chen Ou, Sabunciyan Sarven
The Stanley Medical Research Institute, Rockville, MD, USA.
The Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Transl Psychiatry. 2025 Jul 14;15(1):216. doi: 10.1038/s41398-025-03387-3.
Many epidemiological studies have shown an association between infectious agents, particularly viruses, and psychiatric disorders including schizophrenia. However, evidence of a viral infection in the brain that associates with schizophrenia (SCZ), bipolar disorder (BPD), and major depression (MDD) has not been found. A potential reason for this discrepancy may be that viruses are more likely to infect the neuroepithelium than neural tissue. To test this hypothesis, we used viral sequence enrichment technology and performed RNA sequencing in postmortem choroid plexus (CP) isolated from 84 SCZ, 73 BPD, 23 MDD cases and 76 unaffected controls (CNT) from the Stanley Medical Research Institute brain collection. This approach enabled us to identify the presence of 13 viral species in the CP of 46 subjects. We discovered that CP samples collected from subjects with SCZ and BPD are more likely to contain viral sequences. In terms of individual viruses, the Hepatitis C Virus (HCV) was the only viral species that reached the threshold of statistical significance for an association with SCZ and BPD. Therefore, we focused on HCV to characterize the association between psychiatric disorders and viruses. Analysis of the TriNetX electronic health record database with data on 285 million patients revealed that the prevalence of chronic HCV was 3.6 and 3.9 percent in the SCZ and BPD populations respectively. The prevalence of chronic HCV in these populations was almost double that observed for MDD (1.8%) and approximately 7-fold higher than the control population (0.5%). These findings confirm previous studies that report higher HCV prevalence in SCZ and BPD and suggest that HCV infection may be associated with disease pathology rather than behaviors such as intravenous drug injection, since these behaviors are present in all three disorders. We analyzed hippocampus RNA sequencing data from the subjects identified to be HCV positive via sequence capture. We found that although the virus was absent in this tissue, HCV RNA in the CP was associated with consistent host transcriptional changes in the hippocampus that were potentially related to the innate immune response. Our results are consistent with previous studies and provide clues regarding the contribution of viruses to the pathology of psychiatric disorders.
许多流行病学研究表明，感染因子，尤其是病毒，与包括精神分裂症在内的精神障碍之间存在关联。然而，尚未发现与精神分裂症（SCZ）、双相情感障碍（BPD）和重度抑郁症（MDD）相关的脑部病毒感染证据。这种差异的一个潜在原因可能是病毒更容易感染神经上皮而非神经组织。为了验证这一假设，我们使用病毒序列富集技术，并对从斯坦利医学研究所大脑样本库中分离出的84例SCZ、73例BPD、23例MDD病例以及76例未受影响的对照（CNT）的死后脉络丛（CP）进行了RNA测序。这种方法使我们能够在46名受试者的CP中鉴定出13种病毒的存在。我们发现，从SCZ和BPD受试者收集的CP样本更有可能包含病毒序列。就个别病毒而言，丙型肝炎病毒（HCV）是唯一与SCZ和BPD关联达到统计学显著阈值的病毒种类。因此，我们聚焦于HCV来表征精神障碍与病毒之间的关联。对拥有2.85亿患者数据的TriNetX电子健康记录数据库的分析显示，慢性HCV在SCZ和BPD人群中的患病率分别为3.6%和3.9%。这些人群中慢性HCV的患病率几乎是MDD患者（1.8%）的两倍，约为对照人群（0.5%）的7倍。这些发现证实了先前报告SCZ和BPD中HCV患病率较高的研究，并表明HCV感染可能与疾病病理相关，而非与静脉注射毒品等行为相关，因为这些行为在所有三种疾病中都存在。我们分析了通过序列捕获鉴定为HCV阳性的受试者的海马RNA测序数据。我们发现，尽管该组织中不存在病毒，但CP中的HCV RNA与海马中一致的宿主转录变化相关，这些变化可能与先天免疫反应有关。我们的结果与先前的研究一致，并为病毒对精神障碍病理的贡献提供了线索。
