Revolution In Psychiatry: Hepatitis C Virus Detected In Patients With Schizophrenia And Bipolar Disorder

Research shows that viral infections, such as hepatitis C, may be linked to the onset of mental illnesses such as schizophrenia and bipolar disorder. Scientists have found traces of these viruses in a part of the brain that acts as a protective barrier. While it is not yet clear whether viruses cause these illnesses, there is evidence that they influence brain function and contribute to changes linked to psychiatric disorders.

In recent years, numerous studies have shown that viral infections may be linked to the onset of serious mental illnesses such as schizophrenia, bipolar disorder, and major depression.

Factors such as being born in large cities or at certain times of the year have also been observed as possible influences on this increased risk. These findings have helped to shape the idea that viruses may be involved in the development of psychiatric disorders.

Genetic research has shown that certain regions of our DNA related to the immune system (such as the so-called MHC region) are also associated with these mental illnesses. Furthermore, signs of inflammation, both in the blood and in brain samples from people who died from these disorders, reinforce the idea that infections may play an important role in brain function and the onset of psychiatric problems.

For example, it has been observed that women who had the flu during pregnancy are at greater risk of having children who later develop schizophrenia or bipolar disorder. It has also been noted that people with a history of infection with certain viruses are more likely to develop mental illness.

Even an imbalance in the "brain virome," that is, the viruses present in the brain, has been suggested as a possible factor related to schizophrenia.

Despite all this evidence, there is still no direct, clear proof that a viral infection causes schizophrenia, bipolar disorder, or depression. One reason for this difficulty is that many viruses can remain "hidden" in the body in a latent state, with very few detectable signs.

Furthermore, current technologies have difficulty identifying all types of viruses present in human tissue, especially in the brain.

To overcome these limitations, scientists have developed a new detection method. This technique can more sensitively identify the presence of different viruses in human samples, even when the viruses are present in small quantities. This new approach was initially used in a small study, but it did not have enough samples to draw definitive conclusions.

Another important challenge is knowing exactly where to look for these viruses in the brain. Studies that analyzed a part of the brain called the prefrontal cortex in more than 1,500 people found very few viruses. However, it is known that brain inflammation is a common feature of diseases like schizophrenia. This inflammation can affect cells called endothelial cells, which form part of the brain's protective barrier.

Therefore, researchers at The Stanley Medical Research Institute, USA, decided to study a different, less explored region: the choroid plexus (CPL). This structure forms a sort of filter between the blood and the fluid that bathes the brain (cerebrospinal fluid). It helps protect the brain from invaders, such as microorganisms, and controls the entry and exit of substances.

The choroid plexus is known to be a common target of viral infection, and imaging studies show that it is often enlarged in people with schizophrenia, which may indicate a past infection.

In this study, scientists analyzed choroid plexus samples from 256 deceased individuals, including patients with schizophrenia, bipolar disorder, depression, and also people without mental illness. Using a sensitive detection technique, they looked for signs of viral infection in these samples.

The results were interesting: they identified 13 types of viruses in samples from 46 people. The virus most strongly associated with schizophrenia and bipolar disorder was the hepatitis C virus (HCV).

By cross-referencing this data with a massive healthcare database containing information on 285 million patients, they found that chronic hepatitis C infection was more common among people with schizophrenia (3.6%) and bipolar disorder (3.9%) than among people with depression (1.8%) or without disorders (0.5%).

These findings suggest that the hepatitis C virus may play a role in causing or worsening mental illness, and not simply be present due to risky behaviors such as injection drug use, as this behavior is common in all three groups. However, infection with the virus is more common only in schizophrenia and bipolar disorder.

To further this analysis, the scientists also studied tissue from the hippocampus, a part of the brain involved in memory and emotions, from the same people who showed signs of hepatitis C virus in the choroid plexus. They didn't find the virus directly in the hippocampus, but they observed significant changes in the functioning of cells in this region, possibly in response to the infection detected in the choroid plexus.

This image shows how certain genes behave differently in the brain, specifically in the hippocampus, of people who had the hepatitis C virus (HCV) detected in the choroid plexus (a region that acts as a filter between the blood and the brain). Each graph represents a different gene, with the dots indicating the amount of activity (or "reading") of that gene in different individuals. The black bars show the mean and range of values. "CTL" represents the 33 individuals in the control group, who did not have the hepatitis C virus, while "HCV" represents the 7 individuals who did. The dots also vary in color: the darker the blue, the older the person. Overall, the graphs indicate that several of these genes have lower activity (expression) in people with the hepatitis C virus, suggesting that the virus may be affecting brain function even without being directly present in the brain tissue analyzed.

These results reinforce the idea that viral infections, even if not actively attacking the brain, can affect its function indirectly and persistently. While it's not yet clear whether the hepatitis C virus or other viruses "cause" mental disorders, evidence suggests a link between infection, inflammation, and brain changes that deserves further investigation.

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Association of viral RNAs in the choroid plexus with bipolar disorder and schizophrenia and evidence for the hepatitis C virus involvement in neuropathology

Maree J. Webster, Ashwin Balagopal, Jeffrey Quinn, Ou Chen, and Sarven Sabunciyan 

Translational Psychiatry. volume 15, Article number: 216 (2025) 

https://doi.org/10.1038/s41398-025-03387-3

Abstract: 

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.