Early-Life Adversity and Mitochondrial Function: Comparing Cumulative Risk and Dimensional Models of Adversity

Early-life adversity (ELA) is linked to adverse mental and physical health across the lifespan. Mitochondrial function is one key, but understudied, mechanism that may be relevant for understanding how ELA becomes biologically embedded. Mitochondria are targets of stress response and mediate stress-related pathology, and impaired mitochondrial function is associated with adverse mental and physical health. However, little clinical research has examined ELA and mitochondrial function. We investigated associations of ELA, operationalized by 2 prominent conceptual models (cumulative risk and threat-deprivation dimensions), with mitochondrial function metrics in a community-based sample of trauma-exposed adults.

Participants (N = 143, 55.9% female) reported on ELA experiences, and the information was used to create composites for cumulative ELA and threat- and deprivation-related dimensions. Indices of mitochondrial bioenergetics (oxygen consumption rate, extracellular acidification rate) of live peripheral blood mononuclear cells were assessed with the Agilent Seahorse X96 Extracellular Flux Analyzer. Generalized estimating equations were used to examine associations between cumulative ELA and threat- and deprivation-related dimensions with mitochondrial bioenergetic parameters, adjusting for demographic and technical variables.

Greater cumulative ELA was associated with lower proton leak and ATP (adenosine triphosphate) production rate from glycolysis and greater maximal respiration and reserve capacity. Dimensional analyses revealed unique and nuanced associations between threat- and deprivation-related ELA and mitochondrial parameters.

This is the first study to examine cumulative risk and dimensional models of ELA in relation to mitochondrial function. We shed light on distinct impacts of cumulative ELA and threat- and deprivation-related experiences, highlighting an overall pattern of greater respiratory capacity associated with ELA.