Pre-adolescent Stress and Health Study

Study Overview
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Brief Summary
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Aim 1: To characterize allostatic load (AL) biomarkers in a sample of low-income early adolescents (N = 225). How many children living in low-income homes have atypical or out-of-range biomarker levels, on which biomarkers, and in what combinations (Aim 1a)? Do AL biomarker elevations predict physical and mental health problems in early adolescence (Aim 1b)? How much and what type of change in AL biomarkers occurs between ages 11 and 14 (Aim 1c)? Aim 2: To investigate in the same sample of early adolescents exposed to varying levels of early life stress (ELS), the relative contributions made by ELS, recent (past year), and cumulative (since age 5) stress exposures to initial AL levels at T1 (Aim 2a), and to changes in AL across the two years of the study (Aim 2b). Aim 3: To explore the extent to which coping resources, including children's coping skills, children's physiologic self-regulation, and parental coping socialization, uniquely and synergistically influence AL levels and accumulations in these early adolescents.

Detailed Description
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Childhood adversity is associated with premature diseases of aging, most forms of psychopathology, and early mortality, and chronic stress is a critical mechanism of this phenomenon. Biologically informed interventions are sorely needed to break this pernicious cycle, but very little research has examined potentially malleable psychobiological risk and protective processes during childhood that could be leveraged in interventions. Allostatic Load (AL)-the accumulation of biological insults sustained by the body's attempts to maintain homeostasis in the face of chronic stress-is recognized as one such risk process. Most AL research has thus far been conducted with adults, but the emerging research with adolescents suggests that in-depth examination of AL accumulation processes during early adolescence may yield critical insights needed to develop psychobiologically potent interventions. Coping and self-regulation are potential malleable protective processes, but they have not received much attention in AL research to date. This R01 project will therefore examine the accumulation of AL biomarkers in early adolescence, and will test the contributions of stress (early life, cumulative, recent) and of coping resources (coping skills, parent coping socialization, physiologic regulation) to AL accumulation. In addition, we will examine associations between AL and the emergence of premature diseases of aging (e.g., type II diabetes, metabolic syndrome) by mid-adolescence. Elevated AL biomarkers have been detected in samples of disadvantaged preadolescents (e.g., Evans, 2003; Keller et al., 2012; Rogosch et al. 2011), and are correlated with health problems in this population. Nevertheless, numerous important gaps in our understanding of youth AL processes remain. First, AL is not well characterized in child or adolescent samples. Most existing research involving children focuses only on select aspects of the AL index (such as cortisol), and a comprehensive assessment of the major classes of biomarkers indicated in AL (metabolic, cardiovascular, immunologic, neuroendocrine) in at-risk children is lacking. Second, the absence of clinical benchmarks linking AL to disease in children is a major limiting factor, which coupled with lower base rates of AL-linked diseases in children, calls into question the typical practice of calculating an AL index using adult thresholds (i.e., upper quartile of range). Third, it is unclear to what extent recent and cumulative stressors experienced after the early life period (birth to age 5) contribute to the development of AL over and above early life stress (ELS) in any age group, and many AL studies do not include in-depth assessments of life stress. Fourth, little is known about the extent to which coping resources (youth coping skills, coping socialization) can buffer children from the development and/or worsening of AL over time. This is a critical question as the lead PI's research has shown that coping skills and resources can buffer at-risk children (e.g., in poverty) from common stressors and that coping has effects on primary neuroendocrine mediators of AL such as the HPA (Wadsworth et al., 2016; Bendezu & Wadsworth, 2017). The present project will build on the unique strengths and capacities of the two PIs and their co-investigator and will include state-of-the-art assessments of stress, coping resources, and AL to fully capture these processes at multiple levels of analysis. Two-hundred 11-12 year old Medicaid-enrolled patients will be recruited by experienced pediatric research nurses at Penn State Hershey Hope Drive Pediatrics. Twenty-five additional 11-12 year old patients whose families are not Medicaid eligible will serve as a middle class comparison group for biomarker benchmarking. This research affiliated pediatrics practice conducts 40,000 patient visits per year and enrolls patients from both rural and urban communities across central PA. Youth will be followed across two years and participate in three annual assessments. Biological samples will include blood draws, overnight urine, and saliva samples taken at each time point. Assessments will further include (a) parent and child Youth Life Stress Interviews to obtain indices of early, recent, and cumulative life stress, and (b) the Trier Social Stress Test to measure adolescent SAM and HPA activation patterns and parent coping socialization. Parent-child parasympathetic co-regulation and reports of psychological symptoms, parenting, parent-child attachment, and coping skills will also be obtained. We will examine levels and correlates of AL biomarkers at T1 as well as predictors of the changes that occur between T1, T2, and T3 (AL accumulation). Study aims are as follows: Aim 1: To characterize AL biomarkers in a sample of low-income preadolescents (N = 200). How many children living in low-income homes have atypical or out-of-range biomarker levels (as compared to middle class comparison group) (Aim 1a)? Do prior AL biomarker elevations predict physical and mental health problems at age 13-14 (Aim 1b)? How much and what type of change in AL biomarkers occurs between ages 11 and 14 (Aim 1c)? Aim 2: To investigate in the same sample of preadolescents exposed to varying levels of ELS, the relative contributions made by ELS, recent (past year), and cumulative (since age 5) stress exposures to initial AL levels at T1 (Aim 2a), and to changes in AL across the two years of the study (Aim 2b). Aim 3: To examine how coping resources, including children's coping skills, children's physiologic self-regulation, parent-child attachment, and parent coping socialization, uniquely and synergistically influence AL levels and accumulations in early adolescence.

Official Title
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Pre-adolescent Stress and Health Study

Conditions
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Stress

Intervention / Treatment
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* Other: exposure


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Child Age: 11-12 years (inclusive) at the time of enrollment Sex: male or female Fluent in written and spoken English Parent/Guardian Age: ≥18 years Sex: male or female Fluent in written and spoken English Families incomes ≤ 200% of the 2018 federal poverty line per table below: Exclusion Criteria: Child Age: <11 or ≥13 years at the time of enrollment Cognitive impairment Pregnant (if female) Chronic illness (e.g. psychiatric disorder, cancer or heart disease) or any other medical condition that in the opinion of the investigator disqualifies the subject from participation in the research. Parent/Guardian Age: ≥18 years Cognitive impairment Prisoner

Ages Eligible for Study
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Minimum Age: 132 Months
Maximum Age: 156 Months

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Participants<br>The cohort will consist of male and female children ages 11-12 accompanied by a participating parent over the age of 18 years. The family income of participants in this cohort cannot exceed 200% of the federal poverty level established in 2018. | Other: exposure<br>* exposure to chronic stress<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Allostatic load | represented as individual change across neuroendocrine, autonomic, immunologic, and metabolomic levels among youth from high-risk, rural poor environments | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Child health status | Child health status represented by behavioral, psychological, medical, and physical health outcomes affected by allostatic load. | 2 years |