Epigenetic Age Acceleration and Risk for Depression and Anxiety following Exposure to Substantiated Child Maltreatment

• In Event: Challenges to developing biology and mental health

Abstract

Early life adversity, such as childhood maltreatment, is a well-established neurodevelopmental risk factor affecting one in four children worldwide (Cecil, Zhang & Nolte, 2020) and conferring risks for various forms of psychopathology, including depression and anxiety (Toth & Cicchetti, 2013). Research suggests that epigenetic processes, specifically variation in DNA methylation at stress-sensitive genomic sites, are potential mechanisms increasing the risk for psychopathology for those exposed to early life adversity (Turecki & Meaney, 2016). One powerful indicator of genome-wide variation in DNA methylation is epigenetic age acceleration, a stress-sensitive estimate of the biological aging of cells not attributable to chronological age (Horvath, 2013). A number of studies report accelerated epigenetic aging in individuals with psychiatric disorders, including major depression (Han et al., 2018) and internalizing symptoms in children (Tollenaar et al., 2021). Studies also report associations between DNA methylation in anxiety disorders and related phenotypes (Schiele & Domschke, 2018). However, the majority of studies are based on retrospective data in adults (Cecil, Zhang & Nolte, 2020) and little is known whether early life adversity, including child maltreatment, contributed to accelerated aging in these disorders. A recent study has found that accelerated epigenetic aging only in maltreated children with internalizing disorder but not in non-maltreated children with internalizing disorder (Dammering et al., 2021). Moreover, most studies report only one type of epigenetic age acceleration clock when multiple clocks are now available in the pediatric population.

The objectives of the current study are: 1) examine the association between epigenetic age acceleration and depressive and anxiety symptoms among a sample of children with substantiated maltreatment; 2) examine this association using two different epigenetic clocks: the well-established Horvath clock (Horvath, 2013) and a pediatric buccal epigenetic (PedBE) clock (McEwen et al., 2020) recently developed for application with pediatric samples. Seventy-one children (64.8% female), aged 8-15 years old (M = 11.99, SD = 2.35) and exposed to substantiated child maltreatment within 12 months prior to study entry, were enrolled. Epithelial cheek cells were collected via buccal swab for genotyping and quantification of epigenetic age acceleration within a case-control design. Depressive and trait anxiety symptoms were assessed using the Children’s Depression Inventory and State-Trait Anxiety Inventory for Children, respectively. Lifetime exposure to other childhood adversities, buccal cell count, and gender were entered as covariates. Ordinary least squares regression revealed that epigenetic age acceleration via the Horvath clock was significantly associated with more depressive (b = 1.57, t = 2.038, p = .046) and anxiety symptoms (b = 1.58, t = 2.269, p = .027), while the PedBE clock was not associated with either depressive (b = .53, t = .627, p = .533) or anxiety symptoms (b = -.24, t = -.309, p = .758). Our findings add to existing research and suggest epigenetic age acceleration may be a promising biomarker of depressive and anxiety symptoms among maltreated children. Epigenetic alterations are potentially reversible by various forms of psychotherapy, which underscores the importance of early prevention and treatment to mitigate adverse outcomes of early life adversity.

Authors

• Zhenyu Zhang, Pennsylvania State University, University Park
  Presenting Author

• Kieran O'Donnell, Yale University

• Anneke E. Olson, Pennsylvania State University, University Park

• Lorah D Dorn, Pennsylvania State University, University Park

• Christopher Engeland, The Pennsylvania State University

• Chad Shenk, Pennsylvania State University, University Park