Summary: Researchers have identified hepatitis C virus (HCV) in the choroid plexus—the brain’s fluid-producing lining—of people diagnosed with schizophrenia and bipolar disorder. The virus was detected in the brain lining rather than in brain tissue itself, a finding that suggests infections at the brain’s boundary may influence psychiatric symptoms.
Analysis of large-scale electronic health records confirmed a higher documented prevalence of chronic HCV in people with schizophrenia and bipolar disorder than in those with major depression or in the general population. The results raise the possibility that antiviral treatment might benefit a subset of patients whose psychiatric symptoms are linked to infection.
Key Facts:
- HCV was found in the choroid plexus (the brain lining that produces cerebrospinal fluid), not inside brain tissue.
- People with schizophrenia or bipolar disorder were substantially more likely to have a documented HCV diagnosis than healthy controls.
- HCV in the choroid plexus was associated with altered gene expression in the hippocampus, a region involved in memory and learning.
Source: JHU
Background: For decades, epidemiological studies have linked viral infections to behavioral and psychiatric symptoms, but direct evidence of viruses in the brain of people with psychiatric disorders has been scarce. One explanation is that viruses may preferentially infect the neuroepithelium—the brain’s lining—rather than neural tissue itself.
To investigate this possibility, Johns Hopkins Medicine researchers examined postmortem choroid plexus tissue and analyzed de-identified health records covering 285 million patients. Their study identified HCV sequences specifically in the choroid plexus of individuals with schizophrenia or bipolar disorder, supporting the idea that infections at the brain’s boundary can be present in psychiatric populations.
The study, led by researchers at Johns Hopkins Children’s Center, was published July 14 in Translational Psychiatry.
The Johns Hopkins team, led by neuroscientist Sarven Sabunciyan, Ph.D., analyzed choroid plexus samples from postmortem brains of people diagnosed with schizophrenia, bipolar disorder or major depression, along with samples from unaffected controls. The tissues were obtained from the Stanley Medical Research Institute brain collection, a widely used repository for postmortem psychiatric brain tissue.
Using high-throughput viral sequencing with the Twist Comprehensive Viral Research Panel—an assay designed to detect thousands of viral species—the researchers screened choroid plexus samples for viral RNA. They found a higher overall frequency of viral sequences in samples from individuals with schizophrenia and bipolar disorder, and HCV emerged as the only virus that reached statistical significance in association with those two diagnoses.
Importantly, HCV was detected in the brain lining only in some cases and was absent from the hippocampus and other brain tissues tested, even in individuals known to have chronic HCV infection. This observation indicates that viral presence in the choroid plexus is not automatic in every person with systemic HCV.
HCV is typically acquired through infected blood, causes liver inflammation, and can lead to long-term health consequences. Worldwide, tens of millions of people live with chronic HCV infection, and many infections are asymptomatic. Effective antiviral treatments are available.
In the study’s second phase, the team analyzed TriNetX electronic health records and found that chronic HCV was documented in 3.6% of patients with schizophrenia and 3.9% of patients with bipolar disorder. These rates were nearly double that observed in people with major depression (1.8%) and roughly seven times higher than in a matched control population (0.5%). The investigators controlled for substance use and concluded that differences in illicit drug use did not account for the higher HCV prevalence in schizophrenia and bipolar disorder compared with major depression.
Although HCV RNA was not detected in the hippocampus tissue examined, the presence of HCV in the choroid plexus correlated with consistent changes in hippocampal gene expression. These transcriptional changes involve pathways linked to innate immune responses and could provide a mechanism by which an infection confined to the brain lining influences neural function and behavior.
The authors emphasize that their findings do not imply that all people with schizophrenia or bipolar disorder have HCV. Rather, the results support the presence of HCV in the choroid plexus in a subset of cases and suggest that, for some patients, infection may contribute to psychiatric symptoms. Because HCV is treatable, the researchers propose that screening and antiviral therapy might relieve symptoms in affected individuals and warrant further clinical study.
Sabunciyan and colleagues hope to collaborate with mental health professionals to screen patients with schizophrenia and bipolar disorder for HCV to determine whether treating the infection improves psychiatric outcomes.
Contributing authors from Johns Hopkins University School of Medicine include Ashwin Balagopal, Ou Chen and Jeffrey Quinn; Maree Webster from the Stanley Medical Research Institute is also a co-author.
Funding: This study was supported by grants from the Stanley Medical Research Institute. No conflicts of interest were declared under Johns Hopkins University School of Medicine policies.
About this mental health and neuroscience research news
Author: Kim Polyniak
Source: JHU
Contact: Kim Polyniak – JHU
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Association of viral RNAs in the choroid plexus with bipolar disorder and schizophrenia and evidence for the hepatitis C virus involvement in neuropathology” by Sarven Sabunciyan et al. Translational Psychiatry
Abstract
Association of viral RNAs in the choroid plexus with bipolar disorder and schizophrenia and evidence for the hepatitis C virus involvement in neuropathology
Numerous epidemiological studies report links between infectious agents—particularly viruses—and psychiatric conditions such as schizophrenia. Yet direct evidence for viral infection within the brain associated with schizophrenia, bipolar disorder or major depression has been limited. One possible explanation is that viruses preferentially infect neuroepithelial structures like the choroid plexus rather than neural tissue.
To test this hypothesis, the researchers used viral sequence enrichment technology and RNA sequencing on postmortem choroid plexus tissue from 84 individuals with schizophrenia, 73 with bipolar disorder, 23 with major depression and 76 unaffected controls from the Stanley Medical Research Institute collection. Thirteen viral species were identified across samples from 46 subjects, and choroid plexus samples from schizophrenia and bipolar disorder cases were more likely to contain viral sequences. Among individual viruses, hepatitis C virus reached statistical significance for association with schizophrenia and bipolar disorder.
Further analysis of the TriNetX electronic health record database, containing data on 285 million patients, revealed that chronic HCV prevalence was 3.6% in schizophrenia and 3.9% in bipolar disorder—almost double that observed in major depression (1.8%) and about seven times higher than in the control population (0.5%). These findings support prior reports of elevated HCV prevalence in schizophrenia and bipolar disorder and suggest a potential link to disease pathology rather than to behaviors common across disorders.
Although HCV RNA was absent from hippocampal tissue analyzed, HCV presence in the choroid plexus was associated with consistent host transcriptional changes in the hippocampus, implicating innate immune-related pathways. Overall, the results align with earlier studies and provide new clues about how viruses at the brain’s border may contribute to psychiatric disease pathology.