Does Immune Dysfunction Contribute To Schizophrenia?

Genetic findings from a new study in Biological Psychiatry

Philadelphia, PA, October 10, 2012 – A new study reinforces the finding that a region of the genome involved in immune system function, called the major histocompatibility complex (MHC), is involved in the genetic susceptibility to schizophrenia.

Schizophrenia is among the most disabling psychiatric disorders. Approximately 80% of the risk for developing schizophrenia is heritable, but there has been slow progress in identifying genetic variation that contributes to the risk for schizophrenia.

The current paper contributes to this growing literature by identifying variants of genes that influence the function of the immune system which may contribute to the heritable risk for schizophrenia.

Two large, international, collaborating groups of scientists – the Wellcome Trust Case Control Consortium 2 and the Irish Schizophrenia Genomics Consortium – conducted this new study.

They first performed what is called a discovery scan, where they analyzed over 6 million genetic variants in schizophrenia patients and controls from Ireland. This allowed them to compile a list of variants that showed the strongest association signals with schizophrenia.

They then performed similar work in an independent sample of 13,195 cases and 31,021 controls from around the world in order to search for the same top ‘hits’. This wealth of data was provided by the international schizophrenia genetics community. This replication work is an important scientific strategy, particularly in the field of genetics, to strengthen and support the original findings.

Using these multiple datasets and approaches, their findings lend further support for the involvement of the MHC genes in schizophrenia susceptibility. “In this large collaborative effort, we have replicated evidence for specific risk and protective alleles at the MHC locus - a critical step teasing apart the genetic risk mechanisms involved,” commented Dr. Aiden Corvin, one of the lead authors and a professor at Trinity College Dublin. “However, pinpointing specific risk genes or alleles has been challenging because this is a region of great genomic variation within and between populations.”

These genetic findings also highlight an important gap in our understanding of the biology of schizophrenia. There is a long history of interest in immunologic contribution to schizophrenia including wide ranging observations linking viral infection, gluten sensitivity, changes in cytokine levels in blood and cerebrospinal fluid, and other factors to schizophrenia.

“Despite this, we have relatively little understanding how alterations in immune function are involved in the etiology and pathophysiology of this disorder,” commented Dr. John Krystal, Editor of Biological Psychiatry. “Immunologic studies in schizophrenia that illuminate the nature of the contribution of variation in immune system genes to schizophrenia will be an important new direction in schizophrenia research.”

The article is “Genome-wide association study implicates HLA-C*01:02 as a risk factor at the MHC locus in schizophrenia” by Irish Schizophrenia Genomics Consortium & the Wellcome Trust Case Control Consortium 2 (doi: 10.1016/j.biopsych.2012.05.035). The article appears in Biological Psychiatry, Volume 72, Issue 8 (October 15, 2012), published by Elsevier.
 

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Notes for editors
Full text of the article is available to credentialed journalists upon request; contact Rhiannon Bugno at +1 214 648 0880 orBiol.Psych@utsouthwestern.edu. Journalists wishing to interview the authors may contact Dr. Aiden Corvin at + 353 1 8962468 or acorvin@tcd.ie.

The authors’ affiliations, and disclosures of financial and conflicts of interests are available in the article.

John H. Krystal, M.D., is Chairman of the Department of Psychiatry at the Yale University School of Medicine and a research psychiatrist at the VA Connecticut Healthcare System. His disclosures of financial and conflicts of interests are available here.

About Biological Psychiatry
Biological Psychiatry is the official journal of the Society of Biological Psychiatry, whose purpose is to promote excellence in scientific research and education in fields that investigate the nature, causes, mechanisms and treatments of disorders of thought, emotion, or behavior. In accord with this mission, this peer-reviewed, rapid-publication, international journal publishes both basic and clinical contributions from all disciplines and research areas relevant to the pathophysiology and treatment of major psychiatric disorders.

The journal publishes novel results of original research which represent an important new lead or significant impact on the field, particularly those addressing genetic and environmental risk factors, neural circuitry and neurochemistry, and important new therapeutic approaches. Reviews and commentaries that focus on topics of current research and interest are also encouraged.

Biological Psychiatry is one of the most selective and highly cited journals in the field of psychiatric neuroscience. It is ranked 5th out of 129 Psychiatry titles and 16th out of 243 Neurosciences titles in the Journal Citations Reports® published by Thomson Reuters. The 2011 Impact Factor score for Biological Psychiatry is 8.283.

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