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Epigenetic Changes at Birth Could Explain Later Behavior Problems

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Adult criminality and mental health problems have been linked with fighting, lying, stealing, and other conduct problems (CP) that emerge in children. And these CP have, in turn, been linked with environmental risks and genetic factors—and now, epigenetic changes, too.

The new associations were uncovered by scientists based at King’s College London, who report that epigenetic changes present at birth, in genes related to addiction and aggression, could be linked to conduct problems in children. Moreover, the scientists suggest that their findings could help explain why certain prenatal environmental influences, maternal diet, smoking, alcohol use, and exposure to stressful life events, seem to be related to “early-onset” behavioral problems.

The new findings appeared June 9 in the journal Development & Psychopathology, in an article entitled “Neonatal DNA Methylation and Early-Onset Conduct Problems: A Genome-Wide, Prospective Study.” This article describes how the King’s College scientists examined prospective associations between DNA methylation (cord blood at birth) and trajectories of CP, using data drawn from the Avon Longitudinal Study of Parents and Children.

The scientists considered epigenetic data for children 4–13 years of age. They also measured the influence of environmental factors previously linked to early-onset CP.

“Methylomic variation at seven loci across the genome…differentiated children who go on to develop early-onset (n = 174) versus low (n = 86) CP, including sites in the vicinity of the monoglyceride lipase (MGLL) gene (involved in endocannabinoid signaling and pain perception),” wrote the article’s authors. “Subthreshold associations in the vicinity of three candidate genes for CP (monoamine oxidase A [MAOA], brain-derived neurotrophic factor [BDNF], and FK506 binding protein 5 [FKBP5]) were also identified.”

Essentially, the scientists found that at birth, epigenetic changes in seven sites across children’s DNA differentiated those who went on to develop early-onset CP versus those who did not. Some of these epigenetic differences were associated with prenatal exposures, such as smoking and alcohol use during pregnancy.

One of the genes that showed the most significant epigenetic changes, called MGLL, is known to play a role in reward, addiction, and pain perception. This is notable, as previous research suggests CP are often accompanied by substance abuse, and there is also evidence indicating that some people who engage in antisocial lifestyles show higher pain tolerance. The researchers also found smaller differences in several genes previously associated with aggression and antisocial behavior, including MAOA.

“We know that children with early-onset CP are much more likely to engage in antisocial behavior as adults,” said Edward Barker, Ph.D., the study’s senior author, “so this is clearly a very important group to look at from a societal point of view.”

“There is good evidence that exposure to maternal smoking and alcohol is associated with developmental problems in children, yet we don’t know how increased risk for CP occurs. These results suggest that epigenetic changes taking place in the womb are a good place to start.”

Genetic factors are known to strongly influence CP, explaining between 50% and 80% of the differences between children who develop problems and those who do not. However, little is known about how genetic factors interact with environmental influences—especially during fetal development—to increase the risk for later CP.

Understanding changes in DNA methylation, an epigenetic process that regulates how genes are switched on and off, could aid the development of more effective approaches to preventing later CP.

“Overall, we found that several of the identified sites correlated with prenatal exposures, and none were linked to known genetic methylation quantitative trait loci,” concluded the authors of the Development & Psychopathology paper. “Findings contribute to a better understanding of epigenetic patterns associated with early-onset CP.”

Children who develop early-onset CP—that is, who develop CP before the age of 10—are at a much higher risk for severe and chronic antisocial behavior across their lifespan, resulting in further social costs related to crime, welfare dependence, and healthcare needs.

“Our study reveals significant epigenetic changes that differentiate children who go on to develop CP and those who don’t,” noted Charlotte Cecil, Ph.D., the study’s first author. “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.

“Given that the postnatal environment is also crucial for children’s development, future research should examine whether positive environmental experiences can help to modify these epigenetic changes.”

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