Virus Traces Discovered in The Brain Lining of People With Schizophrenia
Experts have long noted links between these psychiatric disorders and certain viral infections, but direct evidence of the viruses inside human brains is lacking.
In the brain's protective lining, however, the new study found traces of 13 different viral species. HCV showed a significant association with both schizophrenia and bipolar disorder, compared to healthy controls.
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The study, led by researchers at Johns Hopkins University, analyzed postmortem brain samples from patients diagnosed with schizophrenia, bipolar disorder, and major depression, as well as unaffected subjects to serve as controls.
They focused on the choroid plexus, a network of capillaries and connective tissue that controls production of cerebrospinal fluid. This stuff surrounds the brain and spinal cord to cushion against impact, helps remove metabolic waste from the brain, and regulates the exchange of incoming and outgoing molecules.
The choroid plexus is known to be a target for viruses, and since previous studies have found so few viral traces in the brain itself, the authors of the new study deemed this structure a good place for a closer look.
They acquired samples from the Stanley Medical Research Institute collection, a repository of brain tissue to study people with mental health disorders.
To hunt for hidden viruses, the researchers conducted sequencing with the Twist Comprehensive Viral Research Panel, which can help identify more than 3,000 different viruses in human samples.
This revealed an array of viral sequences in the choroid plexus, especially in samples from patients who had schizophrenia or bipolar disorder.
While those samples were more likely to contain viruses in general, HCV was the only viral species with a statistically significant link, the study found.
Thus, the researchers chose it "to characterize the association between psychiatric disorders and viruses," they write.
In a second phase of the study, the authors zoomed out from individual brain samples to analyze TriNetX, a vast database of health records from 285 million patients.
Using these records, they found HCV in 3.5 percent of patients with schizophrenia and 3.9 percent of those with bipolar disorder.
That's nearly twice the prevalence of HCV in patients with major depression (1.8 percent), the researchers note, and seven times the prevalence in the control population (0.5 percent).
The new study found evidence of viruses only in the brain lining, despite also inspecting samples of the hippocampus – a brain region involved with learning, memory, and emotion, among other roles.
The hippocampus was reliably clean, even if the lining wasn't. It appears the protective layer was effectively doing its job of keeping pathogens out of the brain.
Yet patients with HCV in the lining did show altered gene expression in the hippocampus, hinting at how a virus might still wield influence from the brain's margins.
More research is still needed to clarify the associations between viruses and psychiatric disorders, and to explore possible mechanisms that could let pathogens pull strings from the periphery.
Even if HCV can contribute to these conditions, that wouldn't mean it's the only factor. The new findings don't suggest everyone with schizophrenia or bipolar disorder has HCV, the authors point out.
They do, however, offer hope for novel tactics against devastating psychiatric disorders, says Sarven Sabunciyan, a neuroscientist at Johns Hopkins.
"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.
The study was published in Translational Psychiatry.
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