How does the social environment ‘get into the mind’? Epigenetics at the intersection of social and psychiatric epidemiology

Abstract

The social environment plays a considerable role in determining major psychiatric disorders. Emerging evidence suggests that features of the social environment modify gene expression independently of the primary DNA sequence through epigenetic processes. Accordingly, dysfunction of epigenetic mechanisms offers a plausible mechanism by which an adverse social environment gets “into the mind” and results in poor mental health. The purpose of this review is to provide an overview of the studies suggesting that epigenetic changes introduced by the social environment then manifest as psychological consequences. Our goal is to build a platform to discuss the ways in which future epidemiologic studies may benefit from including epigenetic measures. We focus on schizophrenia, major depressive disorder, post-traumatic stress disorder, anorexia nervosa, and substance dependence as examples that highlight the ways in which social environmental exposures, mediated through epigenetic processes, affect mental health.

Methylation of the glucocorticoid receptor gene promoter in bulimic women: Associations with borderline personality disorder, suicidality, and exposure to childhood abuse

“…However, we note that the use of blood-derived tissues to assess psychiatric disorders is increasingly being recognized and a growing body of research is documenting correspondence between brain-and blood-derived gene expression signals 15,38 -highlighting that patterns of epigenetic variation observed in blood are likely to provide a proxy to patterns acting in brain. We also acknowledge that, in the absence of a ''neutral'' control gene, we cannot ascertain that effects we have observed are associated with genespecific epigenetic effects, rather than genomewide influences.…”

“…[13][14][15] One process involved is DNA methylation-the addition of methyl groups to the cytosines of CpG islands (DNA sequences in which a cytosine is followed by a guanine) that are common in the regulatory regions of most genes. Methylated CpGs in genes' promoters reduce access of the transcriptional machinery to the DNA and, in turn, block gene expression.…”

“…Some theorists postulate that epigenetic programming effects, because they produce stable alterations in the DNA transcriptional profile, allow for the principled environmental regulation of gene expression. 15,16 In evidence, variation in early maternal care has been shown to regulate hippocampal GR promoter methylation and GR expression in animals, in a fashion linking neglect to increased methylation, reduced GR gene expression and increased stress reactivity. 17 In parallel, human studies have associated childhood abuse with increased methylation of different GR gene exon-1 promoter variants.…”

“…Based on findings indicating generally altered glucocorticoid functioning in BN, 8,9 and a role of a main GR gene polymorphism in bulimic and associated phenomenology, 6,7 we explored the possibility that women with BN, when compared to noneating-disordered (NED) women, might display propensities toward hypermethylation of the GR gene promoter. We also explored two alternative hypotheses: The first, based on evidence linking developmental stress to altered GR methylation in animals and humans, [15][16][17][18] was that GR gene methylation might be more characteristic of individuals with BN who reported exposure to childhood abuse than of people with BN alone; the second, based on studies associating suicidality 18 and BPD 20,21 with increased GR gene methylation, was that GR methylation might be more pronounced in individuals with BN who also displayed comorbid ''borderline'' or ''suicidal'' manifestations, than of people with BN alone. Guided by previous findings, we targeted CpG sites in GR gene first exon sites 1B, 1C, 1F, and 1H, 16,18 measuring percent methylation at each CpG.…”

How does social support enhance resilience in the trauma-exposed individual?

“…methylation, that turn on or turn off specific genes (Nestler 2012, Toyokawa et al 2012. When a gene is turned on, it produces its gene products, i.e.…”