Dimensions of childhood adversity differentially affect biological aging in major depression

Abstract

Adverse childhood experiences have been consistently linked with physical and mental health disorders in adulthood that may be mediated, in part, via the effects of such exposures on biological aging. Using recently developed "epigenetic clocks", which provide an estimate of biological age, several studies have demonstrated a link between the cumulative exposure to childhood adversities and accelerated epigenetic aging. However, not all childhood adversities are equivalent and less is known about how distinct dimensions of childhood adversity relate to epigenetic aging metrics. Using two measures of childhood adversity exposure, we assess how the dimensions of Maltreatment and Household Dysfunction relate to epigenetic aging using two "second-generation" clocks, GrimAge and PhenoAge, in a cohort of unmedicated somatically healthy adults with moderate to severe major depression (n = 82). Our results demonstrate that the dimension of Maltreatment is associated with epigenetic age acceleration (EAA) using the PhenoAge but not the GrimAge clock. This association was observed using both the Childhood Trauma questionnaire (CTQ; β = 0.272, p = 0.013) and the Adverse Childhood Experiences (ACEs) questionnaire (β = 0.307, p = 0.005) and remained significant when adjusting for exposure to the dimension of Household Dysfunction (β = 0.322, p = 0.009). In contrast, the dimension of Household Dysfunction is associated with epigenetic age deceleration (β = -0.194, p = 0.083) which achieved significance after adjusting for exposure to the dimension of Maltreatment (β = -0.304, p = 0.022). This study is the first to investigate these effects among individuals with Major Depressive Disorder and suggests that these dimensions of adversity may be associated with disease via distinct biological mechanisms.

Trial registration: ClinicalTrials.gov NCT00285935.

Conflict of interest statement

The authors declare no competing interests.

© 2022. The Author(s).

Figures

Fig. 1. Comparison of dimensions of childhood adversity.

Here we show dimensions of adversity assessed in this study (Maltreatment/Household Dysfunction) compared to the dimensions of Threat/Deprivation as assessed by Sumner et al. In parentheses, we show the scales utilized to create these composite scores. Individual items incorporated into each of these domains are shown in the center with arrows indicating to which dimensions they belong. Threat and Deprivation have been assessed using a multi-modal approach, while our study assessed exposures with the commonly utilized Childhood Trauma Questionnaire (CTQ) and Adverse Childhood Experiences (ACEs) questionnaire. We observed that Threat and Maltreatment are highly overlapping with the major differences being inclusion of neglect items and exclusion of witnessing IPV item into the dimension of Maltreatment. Peer victimization (PV) was not assessed in this study as we did not utilize the Violence Exposure Scale-Revised (VEX-R) which provides a measure of different types of peer victimizations experiences. Household Dysfunction and Deprivation were assessed utilizing different scales. #Emotional neglect was assessed in distinct ways between these studies. Specifically, the ACEs/CTQ assesses subjective appraisals of emotional neglect. In prior studies which utilized the Threat/Deprivation framework, emotional neglect was specifically assessed using the Childhood Experiences of Care and Abuse (CECA) which assesses neglectful behaviors (rather than an appraisal of the distant experience of neglect). Cognitive stimulation was assessed using Home Observation Measurement of the Environment (HOME-SF).