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.