The link between schizophrenia and human endogenous retroviruses

Linking schizophrenia and human endogenous retroviruses

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People diagnosed with schizophrenia suffer from symptoms that render them unable to function mentally and socially. These include visual or auditory hallucinations, delusions, confusion, and disorganized thinking and speech. Additional mental health problems include anxiety disorders and/or major depressive illness.

The specific causes of schizophrenia remain unknown. However, several studies suggest that a combination of genetic and environmental factors play a role in its development. There is also a cluster of studies focusing on the hypothetical viral origin of schizophrenia that links the disease with the genetic expression of human endogenous retroviruses. The hypothesis suggests that schizophrenia might be an offshoot of ancient viral infections.

Schizophrenia and the human endogenous retrovirus hypothesis

Endogenous retroviruses are viral elements in the genome of certain species. They are essentially remnants of ancient retroviral infections. In human species, human endogenous retroviruses or HERVs account for at least 5 to 8 percent of the human genome.

A review study by M. Leboyer et al. explained that HERVs found their way in the human genome through the process of evolution. Ancient retroviruses infected ancestral hominids about 2 to 60 million years ago. Note that retroviruses merge with their host cells instead of immediately killing them. This means that an infected cell would carry the genetic code of a particular retrovirus in its cellular DNA, thus replicating and passing the viral elements as it divides and propagates.

Kalliopi Dodou and Paul Whiteley further explained that the addition of these foreign viral elements in the human genome is a result of the evolutionary war with microscopic invaders. This means that HERVs are a product of immune response and subsequent immunity that transpired and developed throughout the timeline of human evolution.

Human endogenous retroviruses do not pose threats to human health according to widespread understanding. Dodou and Whiteley said that the genetic mutations throughout human evolution rendered these viral elements inactive.

Diem et al. further explained that efficient cellular mechanisms such as DNA methylation, chromatic remodelling, post-transcriptional processing, and RNA interference have evolved to restrict the intercellular activities of HERVs.

However, a body of research seems to suggest a correlation between high levels of HERVs expression and specific health maladies, including schizophrenia.

Linking schizophrenia and human endogenous retrovirus transcription

Individuals diagnosed with schizophrenia had elevated transcription of a specific type of HERV called HERV-W according to a review study by Leboyer et al. Blood samples from these patients also contained antigens of HERV-W envelope and capsid proteins. Another review study from Olivia Diem et al. mentioned that transcripts and proteins of HERV-W, ERV9, and HERV-K(HML-2) have been detected in the cerebrospinal fluid of schizophrenic patients.

Perron et al. provided an interesting hypothesis explaining the possible link between schizophrenia and human endogenous retroviruses. They mentioned that HERV-W could be activated during an infection, thus resulting in the production of HERV-W protein. The protein would further stimulate proinflammatory and neurotoxic cascades that can damage the brain and nervous system.

It is also important to mention that HERVs have been associated with different disorders affection behavior and cognitive functions according to Leboyer et al. These include attention deficit hyperactivity disorder and autism spectrum disorder, among others.

Several studies have also explored the possible correlation between infections and a decline in cognitive functions or the development of mental illnesses. Some of these studies hypothesized that infections trigger an autoimmune response that either affects brain activity or directly targets neurons, thus resulting in brain abnormalities and behavioral or cognitive difficulties.

There is also a groundbreaking study that confirms the direct link between the brain and the immune system. Researchers Louveau et al. identified functional lymphatic vessels lining in the dural venous sinuses that link brain with the immune system. This discovery raises numerous questions about the relationship brain functions and immune response.

FURTHER READINGS AND REFERENCES:

  • Diem, O., Schäffner, M., Seifarth, W., & Leib-Mösch, C. 2012. Influence of antipsychotic drugs on human endogenous retrovirus transcription in brain cells. PLoS One. DOI: 10.1371/journal.pone.0030054
  • Dodou, K. & Whitely, P. 2014. We are all part virus—The role of human endogenous retroviruses. The Pharmaceutical Journal. Available: online
  • Leboyer, M., Tamouza, R., Charron, D., Faucard, R., & Perron, H. 2013. Human endogenous retrovirus type W in schizophrenia: A new avenue of research at the gene-environment interface. The World Journal of Biological Psychiatry. 14(2): 80-90. DOI: 10.3109/15622975.2010.601760
  • Louveau, A. et al. 2015. Structural and functional features of central nervous system lymphatic vessels. Nature. 523: 371-341. DOI: 10.1038/nature14432
  • Perron, H. et al. 2012. Molecular characteristics of human endogenous retrovirus type-W in schizophrenia and bipolar disorder. Translational Psychiatry. DOI: 10.1038/tp.2012.125