Mental Disorders and Transgenerational Epigenetics

Epigenetic mechanisms are essential for normal development during embryogenesis and for the differentiation of neural cells. Thus, a precise understanding of epigenetic mechanisms, including DNA methylation and histone modification, is important for elucidating the pathogenic pathways involved in neurodevelopmental disorders. These include various congenital disorders caused by failures of genomic imprinting, X-chromosome inactivation and mutations of the proteins associated with epigenetic gene regulation. Epigenetic mechanisms have been shown to be reversible based on the attachment and detachment of modification factors onto DNA and histone proteins, and recently several lines of evidence have suggested that various environmental factors, including insufficient nutrition, drugs, and mental stress, can alter epigenetic gene regulation in the brain, which potentially causes mental disorders. It was previously believed that epigenetic marks are completely erased during the process of gametogenesis and that they are not transmitted to the next generation. However, several recent lines of evidence obtained from animal studies have suggested that the erasure may not be complete and environmentally-induced epigenomic changes may be inherited by the next generation along with certain phenotypes, including some of the features of mental disorders. In this chapter, the authors present a survey of mental disorders caused by epigenetic aberrations, and discuss epigenetic changes caused by environmental factors, including the possible role of transgenerational inheritance in mental disorders.