As well as genes influencing the exposure and sus- ceptibility to environmental exposures, through GEr and GxE, the reverse association is also possible, and has been postulated in a number of psychi- atric disorders, including depression, schizophre- nia, substance dependence and developmental dis- orders. Epigenetic mechanisms occur when environ- mental factors impact on DNA sequencing (causing de novo mutations) or through changes in DNA methylation and chromatin structure (causing altered gene expression through epimutations) both glob- ally and at the promoters of candidate gene sites.
For example, epigenetic chromatin remodelling of the brain derived neurotrophic factor promoter site (BDNF) is associated with neuronal activity, seizures, chronic stress, cocaine addiction and Rett’s syn- drome: remodelling at the reelin promoter may play a role in mouse models of schizophrenia [101].
Although research on DNA methylation as an epige- netic mechanism underlying GxE is only in its early
stages the preliminary results are promising. Animal studies have shown early maternal behaviour predict the offspring’s stress sensitivity through altered DNA methylation in some key neuronal receptor genes that are involved in the stress response [102]. Environ- mentally induced epigenetic mechanisms may explain a range of epidemiological findings including the age of onset curves, monozygote discordance and the gender differences observed in psychiatric disorders.
Methodologies designed to investigate such epige- netic processes are being developed currently and are likely to further elucidate the gene–environment interplay in psychiatric disorders [103].
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5 Reliability
Patrick E. Shrout
Department of Psychology, New York University, NY, USA