The association between early adversity and negative health outcomes has been established, but the mechanism is poorly defined. Telomere length represents a promising novel epigenetic biomarker of exposure to adversity that implicates cellular aging as a mechanistic biological pathway linking early adversity and negative health outcomes. An objective marker of early adversity would open new research pathways in early adversity research where most current measures of adversity are subjective and vulnerable to bias. The long term goal is to better understand the mechanism by which early adversity alters normal developmental trajectories and to define sensitive periods when exposure alters neurodevelopmental trajectories. The objective of this particular application is to validate telomere length as an epigenetic biomarker of early adversity, define sensitive periods in development that impact telomere length, and provide support for the novel hypothesis that a disruption in cellular aging is one mechanism by which early adversity gets "under the skin." The Bucharest Early Intervention Project (BEIP) is a unique longitudinal study of children exposed to a range of early adversity that has been carefully characterized. The addition of prospective epigenetic measures to this already extensive dataset is expected to add significantly to this study of the cross-domain impact of early adversity and sensitive periods in development related to behavior, social development, emotional development and neurobiology. The central hypothesis is that exposure to early adversity, particularly in the first years of life, alters the rate of telomere attrition. We further expect that telomere length, a known marker of cellular aging, reflects an established measure of neurodevelopment, specifically EEG power. This hypothesis has been formulated on the basis of our preliminary data and review of the literature. The rationale for the proposed research is that telomere length represents an accessible epigenetic biomarker and will advance the study of early adversity by defining an objective measure of exposure. Guided by strong preliminary data, we will test the hypothesis by pursuing three specific aims: 1) To determine the degree to which institutionalization history at specific time points predicts telomere length. 2) To determine the correlation, in a controlled prospective study design, between change in telomere length and ongoing adversity. 3) To examine the association between telomere length and EEG power. This approach is innovative because it examines a novel mechanism in a unique, extensively characterized population of children. The proposed research is significant because it is expected to advance the study of early adversity by providing a novel epigenetic biomarker that can be used across species and across studies. Ultimately, this knowledge has the potential to identify critical developmental periods and reduce the cross-domain negative health effects of early adversity.

Public Health Relevance

The propose research is relevant to public health because the demonstration of an association between telomere length, early adversity, and neurodevelopment in childhood will advance the understanding of the mechanism by which early adversity influences health outcomes across the lifespan. The proposed research is relevant to part of the NIH's mission that pertains defining the biological mechanism linking early adverse environments to negative health outcomes, defining sensitive periods in development, and identifying gender differences is response to adversity. The results will provide fundamental knowledge necessary to decrease the burdens associated with early life adversity.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (ZMH1-ERB-M (02))
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Zehr, Julia L
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Tulane University
Schools of Medicine
New Orleans
United States
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Drury, Stacy S; Mabile, Emily; Brett, Zoƫ H et al. (2014) The association of telomere length with family violence and disruption. Pediatrics 134:e128-37
Drury, Stacy S (2014) Ome's, ic's, and ip's: from the bench to the bedside and back again. J Am Acad Child Adolesc Psychiatry 53:388-91
Drury, Stacy S; Shirtcliff, Elizabeth A; Shachet, Andrew et al. (2014) Growing up or growing old? Cellular aging linked with testosterone reactivity to stress in youth. Am J Med Sci 348:92-100
Theall, Katherine P; Brett, Zoe H; Shirtcliff, Elizabeth A et al. (2013) Neighborhood disorder and telomeres: connecting children's exposure to community level stress and cellular response. Soc Sci Med 85:50-8
Theall, Katherine P; McKasson, Sarah; Mabile, Emily et al. (2013) Early hits and long-term consequences: tracking the lasting impact of prenatal smoke exposure on telomere length in children. Am J Public Health 103 Suppl 1:S133-5