Oxidative Stress and Early Life Adversity: A Pilot Study in High-Risk Adolescent Females

• In Event: 3-175 - Novel Metabolic and Immune Biomarkers of Toxic Stress: New Directions and Considerations for Clinical Translatability

Integrative Statement

Mounting evidence suggests that early life adversity is associated with a wide range of mental and physical health conditions (Feletti et al., 1998) and that metabolic and immune systems are key putative mechanistic pathways underpinning this stress-health relationship (Danese & Baldwin, 2017; Dantzer et al., 2008). Increasing attention has been paid to the role of oxidative stress, which occurs when there is an imbalance between the overproduction of reactive oxygen species and a relative dearth of antioxidant defenses (Maes et al., 2011). Oxidative stress has been linked both to several physical health conditions (e.g., cardiovascular disease and diabetes mellitus; Ceriello & Motz, 2004) and to psychological disorders (e.g., major depressive disorder; Maes et al., 2011) as. However, no study to date has examined links between early life adversity, mental health, and oxidative stress in pediatric populations. The current study aimed to characterize levels of oxidative stress in a high-risk adolescent sample and to explore potential associations with emerging mental health pathology.

Fifty adolescent females were recruited primarily through the Department of Youth Services from a mid-sized urban area in the Pacific Northwest. Participants ranged in age from 14-19 (Mage = 16.3) and the ethnicity of the sample reflects the local community: 62.5% Caucasian, 14.6% mixed race, 8.3% Black or African-American, 6.3% American Indian/Native Alaskan, 4.2% Asian American, and 4.1% other race.

Urine samples were collected and assayed for F2-isoprostanes, a biomarker of lipid peroxidation and oxidative stress. F2-isoprostanes were measured by gas chromatography-mass spectrometry with negative chemical ionization (Walter et al., 2000). Participants completed several self-report inventories including the Adverse Childhood Events Scale [ACEs], which assess forms of abuse, neglect, and household dysfunction (Dube et al., 2003), and the Youth Inventory-4, a DSM-IV reference scale containing 128 items that correspond to the behavioral, cognitive, and affective symptoms of several DSM-IV disorders (Gadow & Sprafkin, 1999). Two standard ordinary least square regression models were run to examine if ACEs predicted elevated F2-isoprostane levels and if F2-isoprostane levels predicted increased mental health symptomatology. Analyses co-varied for age, race/ethnicity, socioeconomic status, and tobacco use. Analyses were adjusted for multiple comparison via Bonferroni correction.

A significant relationship was observed between ACEs and F2-isoprostanes (r=.34, p=.017), such that individuals with four or more ACEs had F2-isoprostane levels .318 ng/mg higher than individuals with fewer than three ACEs (t=2.48, p=.017) (Figure 1). Results revealed that all elevated F2-isoprostane levels were associated with increased number of symptoms across all internalizing disorders (i.e., anorexia nervosa, bulimia nervosa, depressive disorders/dysthymia, and generalized anxiety disorder) (p’s<.001). A composite internalizing score was robustly linked to elevated F2-isoprostane levels (r=.53, p<.011). Attention-Deficit Hyperactivity Disorder was the only externalizing disorder significantly associated with F2-isoprostane levels (r=.46, p<.05) (Table 1).


Results indicate that F2-isoprostanes may represent a global marker of internalizing mental health symptom development and risk in high-risk youth populations. A limitation is that body mass index was not available for this sample. Future studies are required to determine if early life adversity and oxidative stress are independently linked in pediatric samples.

Authors

• Sarah Rachel Horn, University of Oregon
  Presenting Author

• Leslie D. Leve, University of Oregon
  Non-Presenting Author

• Pat R. Levitt, University of Southern California
  Non-Presenting Author

• Philip Fisher, University of Oregon
  Non-Presenting Author