Year : 2015  |  Volume : 57  |  Issue : 2  |  Page : 218-

Epigenetics as a link between psychosocial factors and mental disorders


Jacob Peedicayil 
 Department of Pharmacology and Clinical Pharmacology, Christian Medical College, Vellore, Tamil Nadu, India

Correspondence Address:
Jacob Peedicayil
Department of Pharmacology and Clinical Pharmacology, Christian Medical College, Vellore, Tamil Nadu
India




How to cite this article:
Peedicayil J. Epigenetics as a link between psychosocial factors and mental disorders.Indian J Psychiatry 2015;57:218-218


How to cite this URL:
Peedicayil J. Epigenetics as a link between psychosocial factors and mental disorders. Indian J Psychiatry [serial online] 2015 [cited 2020 Aug 3 ];57:218-218
Available from: http://www.indianjpsychiatry.org/text.asp?2015/57/2/218/158208


Full Text

Previously, based on animal studies (mice and rats), I had suggested that psychosocial factors are involved in the pathogenesis of mental disorders by acting via mechanisms involving epigenetics (heritable changes in gene expression without changes in DNA sequence). [1] Epigenetic mechanisms include DNA methylation and modifications of histones (DNA packaging proteins). Based on human studies, I here provide further evidence that psychosocial factors act via epigenetic mechanisms in the pathogenesis of mental disorders, and suggest that epigenetics is a link between psychosocial factors and mental disorders.

McGowan et al. [2] found that in postmortem hippocampus from suicide victims with a history of childhood neglect/abuse, the gene encoding ribosomal RNA (rRNA) was significantly hypermethylated throughout the promoter and the 5'regulatory region compared to that of control subjects who died suddenly of unrelated causes without a history of childhood abuse/neglect, consistent with reduced rRNA expression in the hypothalamus. Most of the study subjects they included had a history of mental disorder. They later examined epigenetic differences in a glucocorticoid receptor (GR) gene promoter between postmortem hippocampus from suicide victims with a history of childhood neglect/abuse and that from either suicide victims with no such history or controls who had experienced sudden accidental death. [3] They found there were decreased levels of GR gene messenger RNA, and increased DNA methylation of the GR gene promoter in suicide victims with a history of childhood neglect/abuse compared to suicide victims with no such history and control subjects who experienced sudden accidental death. Most of the suicide victims they included had a history of mental disorder. Hence, McGowan et al. suggested that childhood neglect/abuse could have acted epigenetically to contribute to suicide. Beach et al. [4] showed that DNA methylation of the promoter of the gene encoding the serotonin transporter (5-HTT) mediated the impact of child sex abuse on women's antisocial behaviour when they were adults. They studied DNA methylation in cell lines of lymphoblasts obtained from the study subjects, after controlling for direct effects of biological parent psychopathology and 5-HTT genotype. More recently, Smith et al. [5] evaluated African American subjects matched by age and sex, and stratified into four groups by posttraumatic stress disorder (PTSD) diagnosis, and history of child abuse. Total life stress (TLS) was also assessed in all subjects. DNA obtained from peripheral blood was assessed for global and site-specific methylation. DNA methylation levels were examined for association with PTSD, history of child abuse, and TLS, after adjusting for age, sex, and experimental effects. They found that global DNA methylation was raised in subjects with PTSD. DNA in five genes was differentially methylated in subjects with PTSD. Many of these genes have been previously associated with inflammation. In further studies, they found that plasma levels of interleukin-4 (IL-4), IL-2 and tumor necrosis factor-alpha correlated with PTSD, child abuse, and TLS, suggesting to them that psychosocial stress alters global and gene-specific DNA methylation patterns potentially associated with immune dysregulation.

References

1Peedicayil J. Psychosocial factors may act via epigenetic mechanisms in the pathogenesis of mental disorders. Med Hypotheses 2008;70:700-1.
2McGowan PO, Sasaki A, Huang TC, Unterberger A, Suderman M, Ernst C, et al. Promoter-wide hypermethylation of the ribosomal RNA gene promoter in the suicide brain. PLoS One 2008;3:e2085.
3McGowan PO, Sasaki A, D'Alessio AC, Dymov S, Labonté B, Szyf M, et al. Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nat Neurosci 2009;12:342-8.
4Beach SR, Brody GH, Todorov AA, Gunter TD, Philibert RA. Methylation at 5HTT mediates the impact of child sex abuse on women's antisocial behavior: An examination of the Iowa adoptee sample. Psychosom Med 2011;73:83-7.
5Smith AK, Conneely KN, Kilaru V, Mercer KB, Weiss TE, Bradley B, et al. Differential immune system DNA methylation and cytokine regulation in post-traumatic stress disorder. Am J Med Genet B Neuropsychiatr Genet 2011;156B: 700-8.