Early life stress leaves unique biological signatures in cells

New research links childhood adversity to mitochondrial bioenergetic changes later in life, underscoring the impact of stress in early life on cellular health. The study also found that different types of childhood stressors leave unique biological signatures. The findings in Biological Psychiatry, published by Elsevier, add to our understanding of how early-life adversity can impact mental and physical health across the lifespan, informing screening and intervention efforts.

Early-life adversity encompasses experiences that represent deviations from the expected environment and require adaptation, such as physical abuse, sexual abuse, food insecurity, and physical neglect. Recent evidence estimates that 64% of adults in the United States experience at least one adverse event in childhood and adolescence, with nearly one in five (17.3%) reporting four or more events.

Stressful and traumatic experiences impact both mental and physical health. For this study, we focused on mitochondrial function as a potential pathway for the biological embedding of stress. Mitochondria are often thought of as the 'powerhouse of the cell,' but they are much more than that and play a pivotal role in stress-related pathology and biological aging."

Jennifer A. Sumner, PhD, lead investigator, Department of Psychology, University of California, Los Angeles

Despite increasing recognition of the effects of psychosocial stress on mitochondrial function, very little research has examined early-life adversity and the function of mitochondria in living cells. This study is the first to examine early-life adversity and mitochondrial bioenergetics in a diverse sample of adult men and women.

Given the high prevalence of early-life adversity and its important implications for mental and physical health, the investigators examined how early experiences of adversity may impact mitochondria. In a sample of 143 trauma-exposed adults, researchers measured various bioenergetic parameters of live mitochondria using a mitochondrial "stress test." They found that cumulative experiences of early-life adversity were associated with mitochondrial bioenergetic patterns characterized by an increase in respiratory (energy-producing) capacity.

The investigators differentiated between types of trauma: experiences characterized by threat, such as abuse or violence, and deprivation, such as neglect or food insecurity, were differentially associated with markers of mitochondrial function, suggesting that the type of adversity impacts biological health in distinct ways. Threat was associated with lower cellular energy demand and a shift away from glycolysis (the body's process of breaking down sugar [glucose] to create energy), whereas deprivation was linked to increased glycolytic activity and more inefficient energy production, which may indicate greater dysfunction.

Examining distinct early-life adversity dimensions of threat and deprivation in relation to mitochondrial function revealed greater nuance in our understanding of the relationship between early adversity and mitochondrial function.

"We were particularly surprised by the different patterns of mitochondrial function observed across early experiences of threat versus deprivation," comments first author Shiloh Cleveland, MA, Department of Psychology, University of California, Los Angeles. "Elucidating how adversity in childhood and adolescence relates to mitochondrial function could inform targeted intervention efforts earlier in the lifespan to promote positive health outcomes before the onset of age-related diseases."

Dr. Sumner adds, "Our study's findings suggest that taking a more nuanced approach to thinking about experiences of early adversity may help to shed light on distinct mechanisms of the biological embedding of stress."

The investigators note that future research should continue to explore the mechanisms of how early adversity impacts health across the lifespan to inform better intervention and prevention efforts.

John Krystal, MD, Editor of Biological Psychiatry, concludes, "There is growing interest in how cellular dysfunction impacts mental health. This study shows that early childhood trauma leaves a lasting imprint on adult mitochondrial function, pointing to an important pathway through which early-life stress contributes to the biology of psychiatric disorders."