Epigenetic differences in stress response gene FKBP5 among children with abusive vs accidental injuries

Background: Survivors of child abuse experience high rates of adverse physical and mental health outcomes. Epigenetic alterations in the stress response system, the FKBP5 gene specifically, have been implicated as one mechanism that may link abuse to lifelong health issues. Prior studies primarily included older individuals with a remote history of maltreatment; our objective was to test for differential methylation of FKBP5 in children with abusive vs accidental injuries at the time of diagnosis.

Methods: We conducted a cross-sectional pilot study of acutely injured children <4 years old at two children's hospitals (n = 82). Research personnel collected injury histories, buccal swabs (n = 65), and blood samples (n = 25) to measure DNA methylation. An expert panel classified the injuries as abusive, accidental, or indeterminate.

Results: Children with abusive as compared to accidental injuries had lower methylation of the FKBP5 promoter in buccal and blood cells, even after controlling for injury severity, socioeconomic status, and psychosocial risk factors.

Conclusion: These findings suggest that epigenetic variation in FKBP5 may occur at the earliest indication of abuse and may be associated with delayed resolution of the HPA axis stress response. Additional testing for epigenetic differences in larger sample sizes is needed to further verify these findings.

Impact: Children (<4 years old) with abusive compared to accidental injuries showed lower methylation of the FKBP5 promoter in buccal and blood cells at the time of initial diagnosis even after controlling for injury severity, socioeconomic status, and psychosocial risk factors. Early childhood physical abuse may impact the epigenetic regulation of the stress response system, including demethylation within promoters and enhancers of the FKBP5 gene, even at the earliest indication of abuse. The findings are important because unmitigated stress is associated with adverse health outcomes throughout the life-course.