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The epigenetics of child abuse

Yale Medicine Magazine, 2014 - Autumn


Abuse can change the ways in which genes are expressed, leading to alterations throughout the genome.

Children who suffer abuse, neglect, or trauma often develop depression and other psychiatric illnesses. As adults, they have a greater incidence of medical illnesses, including cancer, cardiovascular disease, and diabetes. But then again, many such children escape those dire consequences. What explains who succumbs and who rebounds?

Part of the answer may lie in genetics, and the genetic predispositions of children who show resilience and those who don’t. But part of it may also lie in epigenetics, or how experiences influence gene activity. Epigenetic changes don’t alter the DNA in a gene, but rather how a gene is expressed. A common epigenetic change involves the addition of methyl to the chromatin structure around a gene, which typically suppresses the gene. Different life experiences can increase or decrease methylation through mechanisms researchers are still trying to understand.

“It’s exciting to realize that genetic effects are not fixed and how dynamic the interactions are between genes and the environment,” said Joan Kaufman, Ph.D., associate professor of psychiatry. In a recent collaboration with Joel Gelernter, M.D., a Foundation Fund Professor of Psychiatry, and professor of genetics, and of neurobiology, she compared epigenetic changes in 96 children with a history of early adversity and 96 children without such a history. The researchers focused on differences in the methylation marks in the genomes of these children.

“Based on animal studies elsewhere looking at the effect of maternal neglect, we expected to see epigenetic changes affecting genes involved in the brain’s stress response,” she said. “We were surprised to see them across the entire genome, not only in genes implicated in mental health and psychiatric disorders, but also in cardiovascular disease, diabetes, obesity, and cancer—all health problems long associated with early adversity.”

Epigenetic changes are long term, and these changes may be passed down to children and grandchildren. But the effects of adverse childhood experiences don’t have to be permanent, Kaufman said. The concept of a “critical period” in which a brain pathway becomes fixed has given way to a “sensitive period” when the brain is more susceptible to environmental influences but retains some plasticity. In animals, environmental enrichment has reversed deleterious brain effects mediated by epigenetic changes caused by early deprivation.

“However, to show such reversal in humans,” Gelernter said, “we would have to study the same individual over time to see if the epigenetic markers revert in people who have less pathological outcomes.”

“There’s reason to be optimistic that we could intervene and ameliorate the consequences of early childhood adversity,” Kaufman said.

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