The Major Histocompatibility Complex (MHC) in Schizophrenia: A Review.
Epidemiological studies and mouse models suggest that maternal immune activation, induced clinically through prenatal exposure to one of several infectious diseases, is a risk factor in the development of schizophrenia. This is supported by the strong genetic association established by genome wide association studies (GWAS) between the human leukocyte antigen (HLA) locus and schizophrenia. HLA proteins (also known in mice as the major histocompatibility complex; MHC) are mediators of the T-lymphocyte responses, and genetic variability is well-established as a risk factor for autoimmune diseases and susceptibility to infectious diseases. Taken together, the findings strongly suggest that schizophrenia risk in a subgroup of patients is caused by an infectious disease, and/or an autoimmune phenomenon. However, this view may be overly simplistic. First, MHC proteins have a non-immune effect on synaptogenesis by modulating synaptic pruning by microglia and other mechanisms, suggesting that genetic variability could be compromising this physiological process. Second, some GWAS signals in the HLA locus map near non-HLA genes, such as the histone gene cluster. On the other hand, recent GWAS data show association signals near B-lymphocyte enhancers, which lend support for an infectious disease etiology. Thus, although the genetic findings implicating the HLA locus are very robust, how genetic variability in this region leads to schizophrenia remains to be elucidated.
Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, New York, USA.
Ryan
R
Mokhtari
Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, New York, USA; Department of Genetics, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, New York, USA; Department of Neuroscience, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, New York, USA; Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, New York, USA.
Herbert M
HM
Lachman
MHC; Schizophrenia