Mitochondria and early-life adversity

Abstract

Early-life adversity (ELA), which includes maltreatment, neglect, or severe trauma in childhood, increases the life-long risk for negative health outcomes. Mitochondria play a key role in the stress response and may be an important mechanism by which stress is transduced into biological risk for disease. By responding to cues from stress-signaling pathways, mitochondria interact dynamically with physiological stress responses coordinated by the central nervous, endocrine, and immune systems. Preclinical evidence suggests that alterations in mitochondrial function and structure are linked to both early stress and systemic biological dysfunction. Early clinical studies support that increased mitochondrial DNA content and altered cellular energy demands may be present in individuals with a history of ELA. Further research should investigate mitochondria as a potential therapeutic target following ELA.

Keywords: Early-life adversity; Mechanisms; Mitochondria; Stress; Trauma.

Figure 1.

Mitochondria occupy an intersecting role in stress responses. Early-life adversity (ELA) chronically activates physiological stress responses, coordinated by the cortico-limbic brain network, the HPA axis, the immune system and the metabolic system. Mitochondrial function and structure are altered by stress responses, which in turn exacerbates initial alterations in stress-related physiological systems. This feedforward cycle of dysfunction produces pathology across a variety of biological outcomes. ELA, early-life adversity; HPA, hypothalamic-pituitary-adrenal; mtDNA, mitochondrial DNA; mtDNAcn, mtDNA copy number; ccf-mtDNA, circulating cell-free mtDNA; PFC, prefrontal cortex.