Summary: Researchers have discovered hepatitis C virus (HCV) in the brain lining of individuals with schizophrenia and bipolar disorder, suggesting a possible link between infection and psychiatric symptoms. The study found HCV specifically in the choroid plexus, a structure producing cerebrospinal fluid, but not inside brain tissue itself.
Analysis of medical records confirmed higher HCV prevalence in these disorders compared to controls and major depression. The findings raise hope that antiviral treatments could alleviate symptoms for some patients.
Key Facts:
- HCV was detected in the brain lining—not brain tissue—of people with schizophrenia and bipolar disorder.
- People with these disorders were 7 times more likely to have HCV than healthy controls.
- Infection in the brain lining altered gene expression in memory-related brain regions.
Source: JHU
Observational studies of psychiatric diseases such as schizophrenia, bipolar disorder and major depression have long tied viral infections with behavioral symptoms in these disorders, but scientists have been unable to find direct evidence of suspected viruses in the brain.
Experts say that’s possibly because viruses may not get directly inside the brain, but may target the brain lining instead.
After testing that idea using postmortem human brain samples and the electronic medical records of 285 million patients, a team of Johns Hopkins Medicine scientists says it has found such evidence in the form of the liver-damaging hepatitis C virus in the human brain’s choroid plexus, a collection of cells that make up the lining of the fluid-filled cavities, or ventricles, and — notably — produce the cerebrospinal fluid that protects the brain and spinal cord.
A report on the study, led by investigators at Johns Hopkins Children’s Center, published July 14 in Translational Psychiatry.
The findings confirm previous studies that reported higher than usual hepatitis C (HCV) prevalence in people with schizophrenia or bipolar disorder, and suggest that HCV infections may be associated with the cause of disease rather than behaviors such as intravenous drug use, according to the Johns Hopkins team led by Sarven Sabunciyan, Ph.D., a neuroscientist at the Children’s Center and an associate professor of pediatrics at the Johns Hopkins University School of Medicine.
For the study, the team first analyzed choroid plexus samples from postmortem brains of individuals with schizophrenia, bipolar disorder or major depression, as well as unaffected controls.
The samples were obtained from the Stanley Medical Research Institute collection, a widely used postmortem repository of brain tissue from people with mental health disorders.
They then performed high-throughput sequencing using the Twist Comprehensive Viral Research Panel, a commercial technology that enables identification of more than 3,000 viruses in human samples.
Because previous psychiatric disorder studies had failed to identify viruses inside the brain, the researchers specifically focused on the choroid plexus, which is known as a structure that is targeted by viruses. The analysis revealed the presence of various viruses in the choroid plexus.
The researchers found that more viruses were present in samples from people with schizophrenia or bipolar disorder. But, unlike other viruses, HCV was only present in the brain lining of people who had schizophrenia or bipolar disorder.
Notably, the virus was not present in some individuals who were known to have a chronic HCV diagnosis, suggesting that the infection does not always spread to the brain lining.
HCV infection is common, generally contracted through infected blood, and characterized by inflammation of the liver that can lead to serious complications and even death.
An estimated 50 million people have chronic HCV infections worldwide, with about 1 million new infections occurring each year. About 50% to 75% of cases carry no symptoms. The infections are treatable with antiviral drugs.
Bipolar disorder, characterized by episodes of manic behavior and serious depression, is estimated to have affected approximately 9 in 200 adults in the U.S. at some time in their lives, while schizophrenia, marked by disorganized thinking and hallucinations, and related psychotic disorders are estimated to affect between 1 and 3 in 400 adults in the U.S.
During the next phase of the study, the research team analyzed electronic health records held by TriNetX, and found that HCV was documented in 3.6% of those with schizophrenia and 3.9% of those with bipolar disorder — almost double that of those with major depression (1.8%), and approximately sevenfold higher than the control population (0.5%).
The researchers say while illicit drug use is common among people with all three disorders, drug use did not account for the higher prevalence of HCV in schizophrenia and bipolar disorder compared with major depression.
The team also looked for viral RNA in sequencing data from the hippocampus, a region of the brain that supports learning, memory and other functions, of subjects identified to have HCV, and found that the virus was absent in this tissue despite being present in the brain lining.
However, the presence of HCV in the brain lining altered gene expression in the hippocampus, providing a possible mechanism by which an infection in the lining can affect brain functions and behavior.
While the researchers caution that their study does not suggest that everyone with schizophrenia or bipolar disorder has an HCV infection, they believe their findings provide compelling support for the existence of the virus in the choroid plexus.
“Our findings show that it’s possible that some people may be having psychiatric symptoms because they have an infection, and since the hepatitis C infection is treatable, it might be possible for this patient subset to be treated with antiviral drugs and not have to deal with psychiatric symptoms,” Sabunciyan says.
He says he also hopes to collaborate with mental health professionals to screen for HCV in people with bipolar disorder and schizophrenia to learn whether treating the infection will ease or stop symptoms.
Along with Sabunciyan, authors from the Johns Hopkins University School of Medicine are Ashwin Balagopal, Ou Chen and Jeffrey Quinn. Maree Webster from the Stanley Medical Research Institute was also a co-author.
Funding: This study was funded by grants from the Stanley Medical Research Institute.
No authors declared conflicts of interest 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
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.
