Hepatitis-C Virus Found to Be Associated With Schizophrenia and Bipolar Disorder

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NEWS BRIEF

A recent study found a statistically significant association between hepatitis-C virus (HCV) RNA detection in the postmortem choroid plexus (CP) and psychiatric disease—specifically schizophrenia and bipolar disorder.¹ The findings provide additional clues to the understanding of neuropathology, virology, and inflammation as part of psychiatric disorders.

To further test this finding, investigators used the TriNetX database of 285 million patients and found that chronic HCV was present in 3.6% of the schizophrenia population and 3.9% of the bipolar population, compared to 0.5% in controls. Researchers extracted RNA samples from the choroid plexus of 256 total postmortem individuals who had schizophrenia, bipolar disorder (BD), and major depressive disorder (MDD), along with controls with no psychiatric illness. The control group (N=76) had a mean age of 46 and consisted of 12 females and 64 males. The largest group included individuals (N=84) with schizophrenia group; individuals had a mean age of 44 and an average illness onset at 21 years. It included 27 females and 57 males, and an average illness onset age of 21 years. The BD group (N=73) had an average age of 44 with 34 females, 39 males, and an average onset age of 25. The MDD was the smallest group (N=23) and mean age was 43, with 10 females, 13 males, and an average onset age of 30 years. Any individuals known to be HIV positive or undergoing HIV treatment were excluded from this study.

Compared to a previous study on the same topic, the authors proposed that the viral sequence enrichment approach they used is likely more sensitive and they found more virus instances in fewer participants even with exclusion of endogenous retroviruses. They also conducted analysis of hippocampus RNA sequencing from patients with HCV but found that the virus was absent in the brain tissue. They proposed that because HCV RNA in the CP was still associated with transcriptional changes in the hippocampus, it may be related to immune response. Because of the absence of HCV in brain tissue, researchers also noted that infection of the CP with HCV does not necessarily lead to infection of the brain itself.

Higher prevalence of HCV in BPD and schizophrenia is often assumed to be related to IV drug use and other risky behaviors associated with these disorders. However, this study suggests HCV infection may be associated with disease pathology rather than behaviors such as IV drug injection. Statistically from this investigation, individuals with schizophrenia and BD may be more likely to harbor viruses in their CP. The presence of viruses in the CP in individuals with these psychiatric illnesses is consistent with reported genetic susceptibility to infection in psychiatric disease states. In some patients, viruses in the CP may also be connected to peripheral inflammation.

Ultimately, investigators found an association between HCV RNA detection in the CP and BD and schizophrenia to be statistically significant (chi square p = 0.028). These reported that the findings indicate some patients with schizophrenia and BD are not properly being assessed and treated for HCV, even though guidelines recommend universal screening and treatment..

“Our findings provide compelling support for the viral hypothesis of psychiatric disease and identify HCV as a feasible viral pathogen that contributes to the neuropathology of SCZ [schizophrenia] and [BD],” the authors said. “Given that the worldwide rate of SCZ and [BD] is approximately 1 and 3% respectively, identifying and immediately treating the small subset of patients infected with HCV has the potential to improve psychiatric symptoms for hundreds of thousands of people. Our findings underscore guidance on universal HCV screening and treatment in SCZ and BPD patients for HCV as a part of standard psychiatric care.”

References

1. Webster MJ, Balagopal A, Quinn J, et al. Association of viral RNAs in the choroid plexus with bipolar and schizophrenia and evidence for the hepatitis C virus involvement in neuropathology. Trans Psych. 2025;15(1):216.

2. Mandel E, Biondi MJ, Mendlowitz A, et al. Evaluation of hepatitis C screening and treatment among psychiatry inpatients.J Clin Psychiatry. 2023;84(5):22m14623.