To identify at-risk children precise indicators of the biological changes associated with early life adversity, including prenatal maternal stress (PNMS) and racial disparities are needed. Without reliable indicators capable of providing mechanistic insight the ability to design and implement innovative interventions, and alter negative developmental trajectories, remains limited. Alterations in the stress response system, determined by salivary cortisol levels, are associated with PNMS. Disrupted parent-child attachment, as well as the therapeutic repair of this relationship, has also been found to influence the cortisol response in infants. However, the stress hypo-responsive period in early childhood may limit the utility of cortisol as a stand-alone indicator during this critical developmental time point. Additionally, while cortisol indicates dysregulation in the HPA axis it provides minimal mechanistic information. The established role of genetic and epigenetic factors, including FKBP5 and miRNAs, to both the responsiveness and adaptation of the HPA axis suggest they play an important role in the underlying mechanism. Concurrent measurement of gene expression, miRNA, and cortisol is expected to more robustly define how early adversity is biological embedded. Saliva represents an ideal accessible biological source that reflects an individual's complex internal milieu. Recent evidence indicates that mRNA, miRNA and telomere length can be reliably measured in saliva. Studies have also demonstrated changes in each of these markers with exposure to early adversity and stress. These collective findings indicate that an epigenetic psychophysiological profile concurrently measuring each component is feasible and a critical next step in research seeking to chart the trajectory of mental illness and define the earliest intervention time points. This study expects to enroll infants of African American women with extensive characterization of PNMS and maternal preconception adversity. Saliva will be collected pre and post a known stressor designed to activate the HPA axis at two early developmental time points. Infants will be stressed before (4 months, using the Still Face Procedure) and after (12 months, using the Strange Situation Procedure (SSP)) the development of attachment. The cortisol response to the stressor, fold change in FKBP5 mRNA pre/post the stressor as well as initial levels of miR-134 and miR-16 and telomere length will be determined. Leveraging the increased statistical power associated with propensity score matching this proposal will test the association between PNMS, attachment and salivary markers while controlling for preconception adversity. Achievement of the proposal aims of this proposal is expected to provide enhanced biological evidence in support of the implementation of attachment based interventions early in the life course. The critical need to more effectively address persistent health disparities and decrease the negative health outcomes associated with toxic stress requires the development of innovative methodologies that both define biological mechanisms and track the effectiveness of interventions at the behavioral, physiologic, and molecular level.

Public Health Relevance

The proposed research is relevant to public health because an enhanced mechanistic understanding of the biological embedding of early adversity is ultimately expected to lead to novel interventions and preventive efforts that alter the life-long negative health trajectories associated with toxic stress and health disparities. Thus, the proposed research is relevant to the part of the NIMH's mission that pertains to strengthening the public health impact of NIMH funded research and to charting mental illness trajectories to determine when to intervene.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Study Section
Special Emphasis Panel (ZMH1-ERB-L (04))
Program Officer
Zehr, Julia L
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Tulane University
Schools of Medicine
New Orleans
United States
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Drury, Stacy S; Howell, Brittany R; Jones, Christopher et al. (2017) Shaping long-term primate development: Telomere length trajectory as an indicator of early maternal maltreatment and predictor of future physiologic regulation. Dev Psychopathol 29:1539-1551
Merrill, Livia C; Jones, Christopher W; Drury, Stacy S et al. (2017) The differential impact of oxytocin receptor gene in violence-exposed boys and girls. Int J Dev Neurosci 59:60-67
Jones, Christopher W; Gambala, Cecilia; Esteves, Kyle C et al. (2017) Differences in placental telomere length suggest a link between racial disparities in birth outcomes and cellular aging. Am J Obstet Gynecol 216:294.e1-294.e8
Gray, Sarah A O; Jones, Christopher W; Theall, Katherine P et al. (2017) Thinking Across Generations: Unique Contributions of Maternal Early Life and Prenatal Stress to Infant Physiology. J Am Acad Child Adolesc Psychiatry 56:922-929
Theall, Katherine P; Shirtcliff, Elizabeth A; Dismukes, Andrew R et al. (2017) Association Between Neighborhood Violence and Biological Stress in Children. JAMA Pediatr 171:53-60
Lichtveld, Maureen Y; Shankar, Arti; Mundorf, Chris et al. (2016) Measuring the Developing Therapeutic Relationship Between Pregnant Women and Community Health Workers Over the Course of the Pregnancy in a Study Intervention. J Community Health 41:1167-1176
Fleckman, Julia M; Drury, Stacy S; Taylor, Catherine A et al. (2016) Role of Direct and Indirect Violence Exposure on Externalizing Behavior in Children. J Urban Health 93:479-92
Drury, Stacy S; Scaramella, Laura; Zeanah, Charles H (2016) The Neurobiological Impact of Postpartum Maternal Depression: Prevention and Intervention Approaches. Child Adolesc Psychiatr Clin N Am 25:179-200
Drury, Stacy S; Sánchez, Mar M; Gonzalez, Andrea (2016) When mothering goes awry: Challenges and opportunities for utilizing evidence across rodent, nonhuman primate and human studies to better define the biological consequences of negative early caregiving. Horm Behav 77:182-92
Stacy, Drury; Bruce, Cuthbert (2015) Advancing pediatric psychiatry research: linking neurobiological processes to novel treatment and diagnosis through Research Domain Criteria (RDoC). Ther Innov Regul Sci 49:643-646

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