The role of epigenetics in mental disorders.

It is well established that the idiopathic mental disorders have a genetic basis. Yet, genetic mapping has not definitively identified any genetic mutation or polymorphism underlying these disorders. This review discusses the role of epigenetics in the pathogenesis of the idiopathic mental disorders. Epimutations and epigenetic polymorphisms are emphasized as being an interface between the genes underlying the idiopathic mental disorders and the environment. Psychosocial factors are described as important environmental factors involved in the pathogenesis of the idiopathic mental disorders, modifying the underlying genes by epigenetic mechanisms. Epigenetic strategies to identify the genes underlying the idiopathic mental disorders are described and the available molecular evidence supporting an epigenetic pathogenesis for these disorders is discussed. It also discusses the role of epigenetic factors in the pathogenesis of neuropsychiatric disorders and the relevance of the new therapeutic option, epigenetic therapy, in treating the idiopathic mental disorders and the neuropsychiatric disorders.

Epigenetic therapy--a new development in pharmacology.

Epigenetics, heritable changes in gene expression that do not involve changes in DNA sequence, is known to be involved in disease. Two important epigenetic changes that are known to contribute to disease are abnormal methylation patterns of DNA and modifications of histones in chromatin. This review describes a new development in pharmacology, epigenetic therapy, which attempts to correct these changes. At present two groups of drugs are being developed. One inhibits DNA methyltransferases (DNMTs) resulting in the inhibition of DNA methylation. This group of drugs may prove to be useful in the treatment of cancer where hypermethylation of tumour suppressor genes is known to lead to silencing of these genes. The other group of drugs inhibits histone deacetylases (HDACs) resulting in the accumulation of acetylated histones which are thought to mediate the anticancer effects of these drugs. Both these drug groups have shown promising results in drug trials for the treatment of cancer. Since epigenetic changes are thought to underlie a wide range of diseases, the scope of epigenetic therapy is likely to expand.