WEBB FELLOW: Childhood Adversity, Accelerated GrimAge, and Associated Health Consequences

Background: Childhood adversity is linked to psychological, behavioral, and physical health problems, including obesity and eating behaviors. Epigenetic alterations have been proposed as one pathway through which the effects of early life stress and adversity might persist into adulthood. Epigenetic mechanisms have also been proposed to explain why the health impacts of obesity appear to vary greatly between individuals with similar BMIs. The purpose of this study was threefold: using two independent cohorts, we sought to (1) characterize the relationship between childhood adversity and accelerated aging (GrimAge) in adulthood, (2) examine the link between childhood adversity and obesity and metabolic risk markers, and (3) test moderator effects of accelerated aging on the association between childhood adversity, obesity, and insulin resistance.

Methods: In this study, we examine two independent cross-sectional cohorts of healthy adults, one of which explicitly recruited individuals with early life stress (ELS) and control participants, and the other a general community sample. In these cohorts, we examine associations between childhood adversity, epigenetic aging, and markers of obesity and metabolic health (HOMA-IR). To measure early life stress, we utilized both a dichotomous yes/no classification as well as the Childhood Trauma Questionnaire (CTQ). To measure epigenetic age, we utilized the recently developed epigenetic clock, GrimAge.

Results: We found that childhood adversity predicted increased GrimAge Acceleration in both cohorts, both utilizing a dichotomous yes/no classification as well as a continuous measure using the CTQ. Further investigation demonstrated that CTQ subscales for physical and sexual abuse were associated with increased GrimAge Acceleration in both cohorts, whereas physical and emotional neglect were not. In both cohorts, childhood adversity was also associated with higher BMI and increased insulin resistance as measured by HOMA-IR. Finally, we demonstrate an interaction between GrimAge Acceleration and BMI where, at higher BMIs, GrimAge Acceleration predicts insulin resistance, but not at lower BMIs.

Discussion: These results, which were largely replicated between two independent cohorts, suggest that interactions between epigenetics, obesity, and metabolic health may be important mechanisms through which childhood adversity contributes to long-term physical health effects. While the current study uses cross-sectional data, it suggests that childhood adversity may increase the risk of insulin resistance through epigenetic changes. Prior work has demonstrated that interventions such as DBT (Perroud 2013), escitalopram (Wang 2018), and family-centered prevention programs (Brody 2016) can reverse some epigenetic changes that result from childhood trauma (Thumfart 2022), bringing up the possibility that psychiatric or psychosocial interventions may decrease this risk.

Conclusions/Implications: In individuals with obesity, a history of childhood trauma may increase the risk of metabolic syndrome. Future studies may be able to utilize both psychological and epigenetic markers to identify treatments that will be helpful from both a psychiatric and physical health framework.

References:
Perroud N, et. al.,. Transl Psychiatry. 2013 PMID: 23422958

Wang P, et. al.,. Eur J Clin Pharmacol. 2018 PMID: 29748862

Brody GH, et. al.,. J Child Psychol Psychiatry. 2016 PMID: 26680699

Thumfart KM, et. al.,. Neurosci Biobehav Rev. 2022 PMID: 34742726