Epigenetic Changes Identified In Children Who Develop Early Onset Conduct Problems

MedicalResearch.com Interview with:
Charlotte Cecil, PhD

Edward Barker, PhD

Department of Psychology
Institute of Psychiatry, Psychology& Neuroscience
King’s College London

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Conduct problems (CP) are the most common reason for child treatment referral in the UK, costing an estimated £22 billion per year. Children with CP engage in a range of aggressive and antisocial behaviours (e.g. fighting, stealing, lying), that affect their ability to follow rules and adapt to society, do well in school, and form healthy relationships. Those who do not receive treatment are also at increased risk for many negative outcomes in adulthood, including lower job prospects and earnings, more contact with the police and a lower quality of life. Therefore, it is important to understand how CP develop in the first place, in order to create more effective prevention and intervention strategies.

Studies have found that children who develop conduct problems before the age of 10 (early-onset CP) are at greatest risk for poor outcomes across the lifespan. Compared to other children, those showing early-onset CP tend to have experienced more adversity in early life (e.g. prenatal stress, poverty) as well as having more genetic risk. However, little is known about about how genetic factors interact with environmental influences – especially during foetal development – to increase the risk for early-onset conduct problems.

MedicalResearch.com: What are the main findings?

Response: In this study, we examined whether DNA methylation, an epigenetic process that is sensitive to stress and that regulates the activity of genes, might help us understand how early-onset  conduct problems develop. Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), we found that at birth, DNA methylation levels in seven sites across the genome differentiated children who go on to develop early-onset (n = 174) vs low (n = 86) CP. These changes were located in genes that were involved in a number of biological processes, including neural and immune function. In particular, we identified DNA methylation differences in a gene called MGLL, which has been previously shown to play a role in endocannabinoid signalling in the brain, and regulate pain perception. We also found smaller differences in a number of candidate genes for aggression, including MAOA. Some of these DNA methylation changes were found to correlate with prenatal exposures, such as maternal smoking and alcohol use during pregnancy.

Overall, this study contributes to a better understanding of biological processes related to early-onset conduct problems and provide preliminary support for a link between early adversity, DNA methylation changes and the development of childhood conduct problems.

MedicalResearch.com: What should readers take away from your report?

Response: Our study reveals significant epigenetic changes which differentiate children who go on to develop early-onset conduct problems versus those who don’t. Although these findings do not prove causation, they do highlight the neonatal period as a potentially important window of biological vulnerability, as well as pinpointing novel genes for future investigation.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: We note here three key recommendations for future research.

First, it will be important to replicate our findings in larger samples and establish whether the associations we have observed actually reflect causal effects on the development of conduct problems.

Second, studies are needed to further establish the role of the genes we have identified, to better understand their function and how they may increase risk for early-onset CP.

Finally, it is important to highlight that the postnatal environment is also crucial for children’s development, so that future research should examine whether positive environmental experiences can help to modify these epigenetic changes.

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Charlotte A. M. Cecil, Esther Walton, Sara R. Jaffee, Tom O’Connor, Barbara Maughan, Caroline L. Relton, Rebecca G. Smith, Wendy McArdle, Tom R. Gaunt, Isabelle Ouellet-Morin, Edward D. Barker. Neonatal DNA methylation and early-onset conduct problems: A genome-wide, prospective study. Development and Psychopathology, 2017; 1 DOI: 10.1017/S095457941700092X

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Last Updated on June 14, 2017 by Marie Benz MD FAAD