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Herpesviruses and neuropsychiatric disorders: overlooked adversaries or innocent bystanders?

Neuropsychopharmacology volume 49, pages 313–314 (2024)Cite this article

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Neurotrophic herpesviruses have been linked with neurological and psychiatric disorders for more than 50 years but the idea that these common viruses can cause diseases of brain and mind has traditionally been viewed with skepticism. In some areas of neurology this may be changing. Building on prior epidemiological studies, Bjornevik et al. reported in Science that the risk for multiple sclerosis (MS) was increased 32-fold after infection by Epstein-Barr virus (EBV) and that concentrations of neurofilament light chain, a biomarker of neurodegeneration, were increased only after EBV seroconversion [1]. Using the longitudinal FinnGen and cross-sectional UK Biobank datasets in a discovery/confirmation design, Levine et al. were able to detect replicable associations between 22 different viral exposures and various classes of neurodegenerative diseases including a replication of the EBV-MS association [2]. Further, in the FinnGen dataset, Alzheimer’s disease (AD) was associated with a herpes simplex virus 1 (HSV-1) infection 1–5 years prior to AD diagnosis suggesting a causal relationship.

Our group has focused on cytomegalovirus (CMV), a beta herpesvirus that establishes life-long, latent infections in brain and immune cells and is known to cause neurological disease in immunosuppressed populations. We recently evaluated the effect of CMV serostatus on white matter microstructure and cortical thickness in football players who had sustained a recent concussion and matched uninjured athletes [3]. No CMV effect was observed in the uninjured athletes. However, after propensity-matching for seven potential confounds, CMV positive athletes showed greater axial and radial kurtosis as well as reduced cortical thickness in the aftermath of concussion compared with CMV negative athletes with concussion. Increased kurtosis is thought to reflect increased intra-axonal debris or cellularity of which neuroinflammation is one potential explanation. We hypothesize that the neuroinflammation associated with brain injury is precipitating the reactivation of CMV which is in turn contributing to tissue damage and host anti-viral immune responses, thereby amplifying inflammation [3].

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References

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Funding

Funding

JS acknowledges support from the National Institute of Mental Health (R01MH123652) and the National Institute of General Medical Sciences (P20GM121312).

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Authors and Affiliations

  1. Laureate Institute for Brain Research, Tulsa, OK, 74136, USA

    Haixia Zheng & Jonathan Savitz

  2. Oxley College of Health Sciences, The University of Tulsa, Tulsa, OK, 74119, USA

    Jonathan Savitz

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  1. Haixia Zheng
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  2. Jonathan Savitz
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HZ and JS wrote the paper.

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Correspondence to Jonathan Savitz.

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The authors declare no competing interests.

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Zheng, H., Savitz, J. Herpesviruses and neuropsychiatric disorders: overlooked adversaries or innocent bystanders?. Neuropsychopharmacol. 49, 313–314 (2024). https://doi.org/10.1038/s41386-023-01674-5

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