Mitochondrial Dysfunction in Preschoolers Exposed to Early Adversity

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

Integrative Statement

Accumulating evidence suggests that exposure to childhood maltreatment and other adversities undermines children’s long term mental health, and that accelerated cellular aging may be a mechanism underlying these associations. Mitochondria are the main source of cellular energy and are integral to cellular differentiation, replication, inflammation, and apoptosis (Streck et al., 2014). With aging, mitochondrial function declines and mitochondrial DNA mutations accumulate, particularly in tissues with high energy demands (Gredilla, 2010). Mitochondrial DNA copy number (mtDNAcn) is therefore an indicator of mitochondrial dysfunction and may contribute to altered energy in the brain, increasing risk for psychiatric disorders (Bansal & Kuhad, 2016). Indeed, recent research indicates increased mtDNAcn in adults with a history of childhood maltreatment and psychiatric disorders (Tyrka et al., 2016). We extend this research to examine mtDNAcn in early childhood.

Two hundred and fifty-six preschoolers, including n = 133 with child welfare documentation of moderate-severe maltreatment in the past six months, participated in this study. Preschoolers ranged in age from 3 to 5 years, were racially and ethnically diverse (45% Hispanic; 39% white, 16% black, 23% biracial, 22% other races), and 122 were male. Nearly all children qualified for public assistance (90%). Review of child protection records, semi-structured interviews in the home, and questionnaires were used to assess child maltreatment, traumatic life events, lifetime stress exposure, and child behavior problems. Mitochondrial DNA copy number (mtDNAcn) was measured from saliva DNA using real-time PCR at both a baseline assessment and a six-month follow-up assessment.

Repeated measures general linear models were used to examine the effects of maltreatment and other adversities on mtDNAcn over time. Results demonstrated that a) childhood maltreatment, traumatic life events, and lifetime stress were all positively associated with mtDNAcn at the six-month follow-up assessment (all p’s < .05) but not the baseline assessment; b) traumatic life events was a significant predictor of change in mtDNAcn over time (F(1,252) = 6.48, p = .012) such that children with two or more traumatic life events at baseline had the sharpest increases in mtDNAcn over time compared to children with zero or one traumatic life event (Figure 1); and c) child internalizing, but not externalizing, behavior problems was positively associated with mtDNAcn at both the baseline and follow-up assessments (p’s < .01).

This is the first study to show that mitochondrial DNA copy number is altered in children with maltreatment and other adversities, and the findings are consistent with recent studies of adults. MtDNAcn was also associated with child behavior problems, supporting the perspective that cellular aging is a mechanism underlying the association of maltreatment and psychiatric outcomes. Directions for future research will be discussed.

Authors

• Stephanie H. Parade, Bradley Research Center/Brown University
  Presenting Author

• Kathryn K Ridout, Brown University
  Non-Presenting Author

• Hung-Teh Kao, Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA
  Non-Presenting Author

• Stevie Magnan, Mood Disorders Research Program and Laboratory for Clinical and Translational Neuroscience, Butler Hospital, Providence, RI, USA
  Non-Presenting Author

• Ronald Seifer, Brown University
  Non-Presenting Author

• Barbara Porton, Brown University
  Non-Presenting Author

• Lawrence H. Price, Brown University; Butler Hospital
  Non-Presenting Author

• Audrey R. Tyrka, Brown University/Butler Hospital
  Non-Presenting Author