Summary: A new study sheds light on the role the immune system may play in Schizophrenia.
Source: Lancaster University.
Using data from the largest ever genetic study of schizophrenia, researchers have shed light on the role of the immune system.
It had been suspected that the illness was an autoimmune disorder like multiple sclerosis, Crohn’s or rheumatoid arthritis where the immune system misfires and attacks the body. The international team led by Dr Jennie Pouget from the University of Toronto and Dr Jo Knight from Lancaster University have found strong evidence that schizophrenia is different.
They tested the idea that genetic variants influencing immune function contribute to the disease but they found that the pattern in schizophrenia is not the same as in classic autoimmune disorders.
Among 108 regions of the genome previously linked to the schizophrenia, they found only six which act on both the immune system and the brain.
Jennie Pouget said: “This doesn’t mean that the immune system isn’t involved at all but it could be involved in a completely different way.”
People with schizophrenia show hallmarks of immune diseases such as prior infection and inflammation, supporting the idea that immune disturbances may play a role by disrupting the brain.
However, it is not clear if these immune disturbances are a cause or a consequence of the illness and they themselves could be caused by a combination of genetic and environmental risk factors.
Jo Knight said that the illness was also influenced by the environment.
“For example, we know that schizophrenia is more likely if someone has had a severe infection requiring hospitalisation.
This means that the involvement of the immune system could be environmental, like being exposed to a virus as a fetus in the womb.”
They conclude that schizophrenia does not appear to be an autoimmune disease and that the illness could be caused by environmental risk factors which activate the immune response, like infections or stress, although further research is needed.
Source: Lancaster University
Image Source: This NeuroscienceNews.com image is adapted from the Lancaster University press release.
Original Research: Full open access research for “Genome-Wide Association Studies Suggest Limited Immune Gene Enrichment in Schizophrenia Compared to 5 Autoimmune Diseases” by Jennie G. Pouget, Vanessa F. Gonçalves, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Sarah L. Spain, Hilary K. Finucane, Soumya Raychaudhuri, James L. Kennedy, and Jo Knight in Schizophrenia Bulletin. Published online May 30 2016 doi:10.1093/schbul/sbw059
Genome-Wide Association Studies Suggest Limited Immune Gene Enrichment in Schizophrenia Compared to 5 Autoimmune Diseases
There has been intense debate over the immunological basis of schizophrenia, and the potential utility of adjunct immunotherapies. The major histocompatibility complex is consistently the most powerful region of association in genome-wide association studies (GWASs) of schizophrenia and has been interpreted as strong genetic evidence supporting the immune hypothesis. However, global pathway analyses provide inconsistent evidence of immune involvement in schizophrenia, and it remains unclear whether genetic data support an immune etiology per se. Here we empirically test the hypothesis that variation in immune genes contributes to schizophrenia. We show that there is no enrichment of immune loci outside of the MHC region in the largest genetic study of schizophrenia conducted to date, in contrast to 5 diseases of known immune origin. Among 108 regions of the genome previously associated with schizophrenia, we identify 6 immune candidates (DPP4, HSPD1, EGR1, CLU, ESAM, NFATC3) encoding proteins with alternative, nonimmune roles in the brain. While our findings do not refute evidence that has accumulated in support of the immune hypothesis, they suggest that genetically mediated alterations in immune function may not play a major role in schizophrenia susceptibility. Instead, there may be a role for pleiotropic effects of a small number of immune genes that also regulate brain development and plasticity. Whether immune alterations drive schizophrenia progression is an important question to be addressed by future research, especially in light of the growing interest in applying immunotherapies in schizophrenia.
“Genome-Wide Association Studies Suggest Limited Immune Gene Enrichment in Schizophrenia Compared to 5 Autoimmune Diseases” by Jennie G. Pouget, Vanessa F. Gonçalves, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Sarah L. Spain, Hilary K. Finucane, Soumya Raychaudhuri, James L. Kennedy, and Jo Knight in Schizophrenia Bulletin. Published online May 30 2016 doi:10.1093/schbul/sbw059