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

Area of Science:

• Neuroscience
• Psychology
• Cell Biology

Background:

• Early life adversity (ELA) negatively impacts long-term mental and physical health.
• Mitochondrial dysfunction is implicated in stress-related pathology and adverse health outcomes.
• Little clinical research has explored the link between ELA and mitochondrial function.

Purpose of the Study:

• To investigate the association between ELA, conceptualized as cumulative risk and threat-deprivation dimensions, and mitochondrial function metrics.
• To examine how different models of ELA relate to cellular bioenergetics.

Main Methods:

• Participants (N=143) reported ELA experiences.
• Mitochondrial bioenergetics (oxygen consumption rate, extracellular acidification rate) were assessed in peripheral blood mononuclear cells.
• Generalized estimating equations analyzed associations between ELA dimensions and mitochondrial parameters.

Main Results:

• Greater cumulative ELA correlated with lower proton leak and ATP production from glycolysis.
• Increased cumulative ELA was linked to higher maximal respiration and reserve capacity.
• Dimensional analyses revealed nuanced associations between threat/deprivation ELA and mitochondrial parameters.

Conclusions:

• This is the first study to examine cumulative risk and dimensional ELA models concerning mitochondrial function.
• ELA is associated with distinct impacts on mitochondrial function, showing a pattern of increased respiratory capacity.
• Findings highlight potential biological embedding mechanisms of ELA through mitochondrial pathways.