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The MHC/HLA Gene Complex in Major Psychiatric Disorders: Emerging Roles and Implications

  • Inflammation (M Leboyer, Section Editor)
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Abstract

Purpose of Review

Major psychiatric disorders like schizophrenia and bipolar disorders are etiologically heterogeneous. Gene-environment interactions seemingly constitute the predominant risk mechanism for these conditions. Multiple common and rare genetic variants, sometimes shared, are shown to confer risk to these disorders. Amongst them, the major histocompatibility complex (MHC), known as human leukocyte antigen (HLA) in humans, has emerged as one of the best replicated genetic risk locus of various neuropsychiatric diseases. Herein, we review recent advances regarding MHC’s involvement in the immunopathogenetic pathways of major psychiatric disorders and highlight findings that clearly suggest its determining role in the shared aetiology of schizophrenia and bipolar disorder.

Recent Findings

Converging recent evidence from genome wide association, transcriptomic and imaging genetics studies provide compelling evidence of MHC's involvement in major psychiatric disorders. Some MHC molecules play a cardinal role in neurodevelopment and fine tuning of neuronal plasticity. Dysregulation of MHC expression due to environmental stress or pathological changes could have negative effects on brain and behaviour, including cognition. We highlight possible mechanisms and factors that are crucial in driving MHC-mediated risk of major psychoses.

Summary

This review further emphasizes the importance of MHC gene complex in the aetiopathology of major psychiatric disorders. Although pleiotropic effects of the MHC locus are well known in various disorders, associations with schizophrenia and bipolar disorder are yet to be definitively validated. This calls for further and systematic research, focusing on the genotype-phenotype correlation in these conditions.

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Authors and Affiliations

  1. Department of Human Genetics, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India

    Monojit Debnath

  2. School of Medicine, IMPACT Strategic Research Centre, Barwon Health, Deakin University, Geelong, Victoria, Australia

    Michael Berk

  3. Orygen, The Centre of Excellence in Youth Mental Health, the Department of Psychiatry and the Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, Australia

    Michael Berk

  4. DHU PePSY, Department of Psychiatry of Mondor Hospital, INSERM, U955, Psychiatrie Translationnelle, Fondation FondaMental, University Paris Est Créteil, Créteil, France

    Marion Leboyer & Ryad Tamouza

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  1. Monojit Debnath
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  2. Michael Berk
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  3. Marion Leboyer
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  4. Ryad Tamouza
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Correspondence to Monojit Debnath or Ryad Tamouza.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Inflammation

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Debnath, M., Berk, M., Leboyer, M. et al. The MHC/HLA Gene Complex in Major Psychiatric Disorders: Emerging Roles and Implications. Curr Behav Neurosci Rep 5, 179–188 (2018). https://doi.org/10.1007/s40473-018-0155-8

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  • DOI: https://doi.org/10.1007/s40473-018-0155-8

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