title: Is DNA methylation responsible for immune system dysfunction in schizophrenia?
abstract: Association of both environmental and hereditary factors in susceptibility to schizophrenia is well established. Initial diagnosis of schizophrenia in a genetically susceptible individual usually occurs the first time that individual faces a great life-time stressful event. Immune system dysfunction is one of the major factors implicated in the etiology of schizophrenia because it can render an individual more vulnerable to stress. Imbalance between type-1 and type-2 immunity and subsequent alterations in cytokine levels have been reported in schizophrenia patients. Cytokines seem to have neurotropic activities associated with neurologic disorders, suggesting their complex role in the central nervous system (CNS). On the other hand, it is well known that CpG methylation strongly associates with silencing of genes in differentiated cells at the transcriptional level and variation in genomic DNA methylation of cytokine genes and T cells is an important factor modulating cytokine gene expression in various conditions. Therefore, it could be hypothesized that alterations in methylation pattern of selective cytokine gene promoters be regarded as an underlying mechanism of Th1/Th2 imbalance observed in schizophrenia. Environmental triggers including feto-maternal transmission of viral or bacterial micro-organisms, change in enzymatic activities, or interaction of environmental and genetic factors in individuals with a higher risk of schizophrenia might orchestrate this mechanism.
authors.affiliation: Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Khojasteh-Fard
authors.forename: Mina
authors.initials: M
authors.lastname: Tabrizi
authors.forename: Mahsa M
authors.initials: MM
authors.lastname: Amoli
mesh_terms: D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D006801:Humans; D007107:Immune System / Q000503:physiopathology*; D007249:Inflammation / Q000503:physiopathology; D012559:Schizophrenia / Q000235:genetics / Q000503:physiopathology*