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

AbstractPurpose of ReviewMajor 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 FindingsConverging 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.SummaryThis review further emphasizes the importance of MHC gene complex in the aetiopathology of major psychiatric disorders. Althoug...
Source: Current Behavioral Neuroscience Reports - Category: Neuroscience Source Type: research