DNA methylation changes in schizophrenia and bipolar disorder

The etiology of the major psychotic disorders, including schizophrenia and bipolar disorder, remains poorly understood. Postmortem brain studies have revealed altered expression of multiple mRNAs, affecting neurotransmission, metabolism, myelination and other functions. Epigenetic mechanisms could be involved, because for a limited number of genes, the alterations on the mRNA level were linked to inverse DNA methylation changes at sites of the corresponding promoters. However, results from independent studies have been inconsistent and when expressed in quantitative terms, disease-related methylation changes appeared to be comparatively subtle. A recent study identified approximately 100 loci with altered CpG methylation in schizophrenia or bipolar disorder, the majority of which were gender-specific. Additional work will be necessary to clarify the origin and timing of these methylation changes in psychosis, and to determine the specific cell types affected in CNS.