Influence of DNA Methylation on Mental Health

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Week 7 - What is known about epigenetic effects of the rearing environment on mental health?

Extensive epidemiological studies suggest that adult disease risk is associated with adverse environmental conditions early in development. In the mid-to-late 2000s, the mechanisms behind these relationships were unclear, but it was hypothesised that epigenetic dysregulation was involved. By 2013, DNA methylation emerged as a potential mechanism for mediating genetic and environmental effects. Early life environmental conditions contribute to the prevalence of ADHD, it is widely known that presynaptic genes are the most important components in the aetiology of ADHD (Gizer et al., 2009). This led to an investigation into whether newborn DNA methylation patterns of specific candidate genes were associated with ADHD symptoms in childhood (van Mil et al., 2014).

For the present study conducted by van Mil and colleagues (2014), 11 regions at 7 different genes were selected as candidate genes, and they were either neuronal or non-neuronal. In the overall analysis, DNA methylation levels of candidate genes were negatively associated with ADHD symptom scores. Wong and colleagues (2010) described epigenetic differences in twins in the DRD4 and 5-HTT genes. The present study found that the relationship between lower levels of DNA methylation and more ADHD symptoms could be largely explained by associations of DRD4 and 5-HTT regions.

In previous reports of patients with psychiatric disorders, patients were more likely to have neuronal candidate genes (Frieling et al., 2006; Abdolmaleky et al., 2008); which supports the study's findings. Changes in DNA methylation is reported to influence the aetiology of bipolar disorder, autism, and OCD, among others. We can conclude that the observed associations in this present study may not be specific to ADHD. Thus, all psychiatric genes have implications in numerous developmental disorders. Further research is needed to confirm the results from van Mil and colleagues (2014) and to further investigate the possible underlying mechanisms for mediating genetic and environmental effects, aside from DNA methylation.

References

Abdolmaleky, H. M., Smith, C. L., Zhou, J. R., & Thiagalingam, S. (2008). Epigenetic alterations of the dopaminergic system in major psychiatric disorders. In Pharmacogenomics in Drug Discovery and Development: From Bench to Bedside (pp. 187-212). Totowa, NJ: Humana Press.

Frieling, H., Römer, K. D., Wilhelm, J., Hillemacher, T., Kornhuber, J., de Zwaan, M., ... & Bleich, S. (2006). Association of catecholamine-O-methyltransferase and 5-HTTLPR genotype with eating disorder-related behavior and attitudes in females with eating disorders. Psychiatric genetics, 16(5), 205-208.

Gizer, I. R., Ficks, C., & Waldman, I. D. (2009). Candidate gene studies of ADHD: a meta-analytic review. Human genetics, 126(1), 51-90.

van Mil, N. H., Steegers-Theunissen, R. P., Bouwland-Both, M. I., Verbiest, M. M., Rijlaarsdam, J., Hofman, A., ... & Tiemeier, H. (2014). DNA methylation profiles at birth and child ADHD symptoms. Journal of psychiatric research, 49, 51-59.

Wong, C. C. Y., Caspi, A., Williams, B., Craig, I. W., Houts, R., Ambler, A., ... & Mill, J. (2010). A longitudinal study of epigenetic variation in twins. Epigenetics, 5(6), 516-526.

This was a fun one to write, I hope you enjoyed reading it as much as I enjoyed researching for this blog post.

Signing off,

burnt toast, sweet tea;