Psychosis-associated environmental exposures may result
Psychosis-associated environmental exposures may result in long-lasting epigenetic alterations that impact on the neurobiological processes involved in pathology (Rutten and Mill, 2009). Dempster et al. (2011) performed a genome-wide analysis of DNA methylation on peripheral blood DNA samples obtained from MZ twin pairs discordant for major psychosis. Their results revealed disease-associated DNA methylation differs between twins discordant for schizophrenia and bipolar disorder individually and together as a combined major psychosis group.
Pathway analysis of our top loci highlighted a significant enrichment of epigenetic changes in biological networks and pathways directly associated with psychiatric disorder and neuro-development. Their data provided further evidence to support the role of DNA methylation differences in mediating phenotypic differences between MZ twins and in the etiology of both schizophrenia and bipolar disorder (Dempster et al., 2011). The understanding of epigenetic modifications and their potential for reversibility is therefore crucial for clinical psychiatry and may lead to the development of novel and innovative solutions for prevention and/or intervention (Rutten and Mill, 2009).
Along the same line, Mastroeni, McKee, Grover, Rogers and Coleman (2009) examined DNA methylation of monozygotic twins discordant for Alzheimer’s disease. Interestingly, they found significantly reduced levels of DNA methylation in temporal neocortex neuronal nuclei of the AD twins. These findings are consistent with the hypothesis that epigenetic mechanisms may mediate, at the molecular level, the effects of life events on AD risks and provide, for the first time, a potential explanation for AD discordance despite genetic similarities (Mastroeni, McKee, Grover, Rogers, and Coleman, 2009).
It is thus obvious that MZ twin pairs share a virtually identical genome but often differ in their susceptibility to mental disorders (Petronis, 2006). There has been considerable interest in the DNA methylation changes in monozygotic twins who are discordant for mental disorders (McGowan and Szyf, 2010). An example of a mental disorder variation is the variation in DNA methylation observed between MZ twins discordant for schizophrenia and bipolar II disorder (Petronis et al., 2003; Kuratomi et al., 2007).
When taken together, the evidence of the differences in DNA methylation between MZ twins could contribute to the discordance of mental disorders. As mentioned earlier, epigenetic modifications were reported to increase with age in MZ twins. This validates the fact that the observed epigenetic alterations in discordant MZ twins is not merely related to the etiology of the disease, but also to the epigenetic drift addressed earlier (Fraga et al., 2005).
Although epigenetic marks are established early during development and differentiation, adaptations occur throughout life in response to intrinsic and environmental stimuli which also mediate different cancers. In other words, epigenetic changes are now known to play a key role in most kinds of cancer both in the early and late stages of the disease (Esteller, 2007). Heyn et al. (2013) investigated the levels of DNA methylation in the blood of 36 pairs of twins diagnosed with and without breast cancer.
They identified an epigenetic alteration of 403 differentially methylated CpG sites in the MZ twin who will develop breast cancer (but not in the healthy one) by using whole blood from 15 twin pairs discordant for breast cancer and high-resolution DNA methylation analysis. Additionally, they found DNA hyper-methylation of the promoter region in primary breast cancer tissues and cancer cell lines. They concluded that hyper-methylation of DOK7 occurs years before tumor diagnosis. Their results are suggestive of a powerful epigenetic blood-based biomarker’s role and enhance the knowledge regarding breast cancer pathogenesis. However, further research is needed to understand the exact function of the DOK7 gene that could lead to preventative treatment (Heyn et al., 2013).
Further, MZ twins discordant for Type 2 diabetes constitute an ideal model for studying environmental contributions to type 2 diabetic traits. Ribel-Madsen et al (2012) examined whether global DNA methylation differences exist in major glucose metabolic tissues by collecting skeletal muscle and subcutaneous adipose tissue biopsies from 53-80 year-old monozygotic twin pairs discordant for type 2 diabetes. Their study suggested that acquired DNA methylation changes in skeletal muscle or adipose tissue gene promoters were quantitatively smaller between Type 2 diabetic and non-diabetic twins (Ribel-Madsen et al., 2012).
