In the mid 1950s, C.H. Waddington revolutionized the field of developmental biology by merging the theories of genetics and development. Previously developmental genetics and its mechanisms were studied separately but Waddington focused on the interplay between genetic factors and embryological growth and differentiation. He coined the term “epigenetics” to describe this novel area.1
Today, “epigenetics” is used to describe “the study of stable alterations in gene expression potential that arise during development and cell proliferation.” Epigenetic processes underlie embryonic cellular development and differentiation, but they are also important in mature mammals, either at random or under influence of the environment (for review see2
). One area in which this is of special importance is the field of psychiatry as emerging evidence suggest that epigenetic mechanisms influence normal patterns of neurodevelopment and cerebral function (for review see ref. 3
), as well as the aberrant neurodevelopment in psychiatric disorders.4
The epigenetic machinery is extensive and complex and to date not fully understood. Central to our understanding is that epigenetic mechanisms influences transcription of DNA my modifying access to the DNA sequences. depicts the epigenetic mechanisms that are important for this review. Within the nucleus of a cell, the DNA sequence lies wrapped around histone proteins. The complex of DNA, histones and non-histone proteins, such as scaffold and polycomb proteins, forms a highly condensed structure called chromatin. The basic unit of chromatin is the nucleosome. Each nucleosome is connected to the next by a short segment of linker DNA to which a histone H1 protein binds. The string of nucleosomes is folded into a strongly condensed fiber bringing about a strong compaction. Several details on the folding of the nucleosome string are still elusive, and in particular the higher order structure of chromatin is not fully understood. Within the chromatin structure, the DNA sequence is methylated at certain nucleotides. The methylation pattern of DNA across the genome together with the chromatin structure is referred to as the epigenome. As in other cells, epigenetic mechanisms are essential to the development of the nervous system. The epigenetic machinery drives both embryonic and postnatal neural development. It is involved in neurogenesis,5,6
neuronal differentiation, cell fate specification7
and development of dendrites.8
Interestingly, the course of development of the epigenetic profile is influenced by environmental factors in utero. In different species environmental factors such as temperature or the presence of predators, have been shown to affect the phenotype of the offspring. In humans and mice, the physiology of the baby is affected by the nutritional state of the mother9
and maternal stress in rats also alters the phenotype of their offspring.10
Such epigenetic developmental plasticity may involve preparing the offspring for the type of environment in which they are likely to live11
but aberrant epigenetic regulation may also lead to disease. Emerging evidence now suggests that vulnerability to psychiatric disorders such as depression and schizophrenia is modulated by epigenetic processes (for review see refs. 12
AUTHOR: Please provide figure legend.
It was previously thought that the epigenetic marks obtained in utero remain the same over time. However, it is now clear that these mechanisms are dynamically regulated. Epigenetic remodeling takes place throughout adult life, under the influence of environmental factors such as nutrition, drugs, and chemical, physical and psychosocial factors (for review see ref. 14
). The reversible nature of epigenetic marks and their susceptibility to environmental influences makes them potential targets for therapeutic interventions. Indeed, in the past decade many drugs including known psychotropic drugs were found to exert an influence on the epigenome. Therefore, the aim of this review is to summarize the current state of knowledge regarding drug-induced alterations of the epigenome in order to provide insight in this developing field.