Epigenetic changes in the regulation of key stress gene detected in kids with abusive injuries

Reviewed by Emily Henderson, B.Sc.Mar 2 2023

Epigenetic changes in the regulation of a key gene in the body's stress response system were detected in babies and young children with abusive injuries, as opposed to accidental, according to a pilot study published in the journal Pediatric Research.

The epigenome influences levels of gene expression in response to the physical, social and emotional environment, without altering the DNA sequence. Multiple studies in adults have found that traumatic and adverse childhood experiences are associated with epigenetic alterations in the FKBP5 gene, an important regulator of stress response.

This study is the first to find epigenetic changes in the FKBP5 gene at the time of diagnosis in cases of abuse, regardless of injury severity, socioeconomic status, or psychosocial risk factors.

The epigenetic differences we found in young children who suffered injuries from abuse were striking and may reflect prolonged toxic stress from living in a truly dangerous environment. Unfortunately, the story doesn't end there. Unmitigated stress is linked to adverse health outcomes in adulthood and survivors of childhood abuse experience higher rates of cardiovascular disease, diabetes, cancer, as well as mental health problems."

Mary Clyde Pierce, MD, Senior Author, Emergency Medicine physician at Ann & Robert H. Lurie Children's Hospital of Chicago and Professor of Pediatrics at Northwestern University Feinberg School of Medicine

In the United States, child abuse affects over 650,000 children each year.

The study included 82 acutely injured children younger than 4 years old. An expert panel classified the injuries as abusive, accidental, or indeterminate. Cheek swabs and blood samples were gathered to measure DNA methylation of the FKBP5 gene (a chemical change that regulates gene activity).

Dr. Pierce and colleagues found that children with abusive injuries had lower methylation of the FKBP5 gene promoter area, which typically correlates with increased gene expression.

"The dysregulation of the stress gene we observed at diagnosis suggests that the biological response to abuse starts very early," said Dr. Pierce. "It is possible, however, that early interventions could reverse the epigenetic alterations in the stress system. More research is needed to confirm our findings and potentially identify an epigenetic signature to see if interventions are working."

Research at Ann & Robert H. Lurie Children's Hospital of Chicago is conducted through Stanley Manne Children's Research Institute. The Manne Research Institute is focused on improving child health, transforming pediatric medicine and ensuring healthier futures through the relentless pursuit of knowledge. Lurie Children's is ranked as one of the nation's top children's hospitals by U.S. News & World Report. It is the pediatric training ground for Northwestern University Feinberg School of Medicine. Emergency medicine-focused research at Lurie Children's is conducted through the Grainger Research Program in Pediatric Emergency Medicine.