Katherine P. Theall, PhDTulane UniversitySchool of Public Health and Tropical Medicine
The Pennington Biomedical Research Center Childhood Obesity & Public Health Conference
October, 2015
Biologic Embedding ofNeighborhood-Level Stress in Children
Outline
• Adverse childhood experiences (ACE), Life Course and Toxic Stress▫ Neighborhood context
• Biological ‘embedding’ and empirical evidence▫ Telomere length
• Implications for obesity and chronic disease risk
Disclosures: no financial conflicts
• Funding: R01ES020447 (NIEHS)* K01SH000002 (CDC) R01 MH101533 (NIMH & NIMHD supplement, Drury)* Tulane Oliver Fund* Frost Foundation* R21 MH094688 (NIMH, Drury) Tulane Research Enhancement Fund
* current
Parents are important Trauma is not good Lots of things effect
kids Kids are different from
each other Kids are different
from adults
A couple of obvious points….
Conceptual Model – Neighborhoods & Obesity
Neighborhood Conditions
Family/Household Conditions
Biologic Stress / Telomere Length
Obesity / Overweight
Biologic Stress / Telomere Length
Individual Characteristics
FamilyMicrosystem
PeerMicrosystem
NeighborhoodMicrosystem
SchoolMicrosystem
Macrosystem
Exosystem
Bronfenbrenner’s Ecological Theory
Abuse
Household Dysfunction
(e.g., substance abuse, mental illness, IPV)
Neglect Support and Praise
Tis but a scratch
Why Children?
Critical or Sensitive Periods (Fine and Kotelchuck, 2010)
Impact of adverse experience may be greatest at specific critical or sensitive periods of development (e.g. during fetal development, in early childhood, during adolescence) Sensitive – more able to reverse or change vs. critical
period
Biological embedding
Accumulation Models (Kuh and Shlomo, 2004)
The accumulation of adverse experiences matter
Life Course Concepts ‘T2E2’
• Timeline – health is cumulative and longitudinal, i.e., developed over a lifetime.
• Timing – health and health trajectories are particularly affected during critical and sensitive periods.
• Environment – the broader environment (social, physical, economic) affects health and development.
• Equity – health inequality (inequity = unjust) reflects more than genetics and personal choice.
– Fine and Kotelchuck
Three levels of stress:
• Positive stress ▫ Brief increases in heart rate, mild
elevations in stress hormones• Tolerable stress▫ Serious, temporary stress response
buffered by supportive relationships• Toxic stress▫ Prolonged activation of the stress
response systems in the absence of protective relationships
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Center on the Developing Child Working Paper: Excessive Stress Disrupts the Architecture of the Developing Brain
Adverse early experience
Altered stress Response systems
Altered neurodevelopmentalTrajectories/circuits/synapses
Altered behavioral,psychological,
cognitive and healthoutcomes
Genetic variation
Environment
Telomeres ????
Early life adversity
DNAHealth
Telomere basics – Beginning of the End
• Links with diseases:▫ Obesity▫ Cardiovascular▫ Dementia▫ Diabetes▫ Mental illness
• Links with environment:▫ Caregiving stress▫ Violence▫ Abuse▫ Lead and other toxins▫ Radiation
…similar to the negative health outcomes associated with adverse childhood events
Telomeres as sensors and antennas
Systemic Level: Paths to Cell Aging
Biochemical Stressors
Cortisol
Cytokines
Insulin
Oxidative Stress
Adiposity
Telomere and Telomerase
Maintenance System
Threat perception and brain response
Epel, Hormones, 2009
Mitochondrial Damage
Oxidative Stress
Youth studies and telomere length
• Diseases▫ Obesity▫ Diabetes▫ HIV ▫ Autism
• Environment▫ Institutional care▫ Abuse and maltreatment▫ Community disorder▫ Family instability▫ Lead▫ Parental education▫ Prenatal smoking▫ Neighborhood violence*
• Biological ▫ HPA/ANS reactivity▫ Testosterone▫ DHEA*
• Transgenerational▫ Parental alcoholism*▫ Maternal obesity*
*in preparation/under review
Why Neighborhoods?• Diseases▫ Obesity▫ Cardiovascular disease▫ Mental health▫ Mortality
• Environment▫ Domestic violence▫ Health behaviors (e.g. smoking, physical activity)
• Biology▫ Adverse birth outcomes, low birth weight ▫ Biological stress, e.g., telomere length, cortisol
PUBLIC HEALTH IMPACT!
National Adolescent Sample
• Research Question:▫ Is the neighborhood crime risk environment
and cumulative neighborhood risk (e.g., crime, alcohol outlet density, concentrated disadvantage) associated with physical activity (PA), obesity/overweight, and allostatic load (AL)?
▫ Is the relation moderated by sex?
PA classified as engaging in vigorous or moderate physical activity in last week; obesity/overweight based on age-for-sex CDC growth charts; AL based on 9 biomarkers across multiple systems.
National Health and Nutrition and Examination Survey (NHANES)
• Continuous Surveys 1999 – 2006▫ Cross-sectional, biennial surveys (4 waves)▫ In-home survey, medical exam, laboratory
• Adolescents age 12 – 20 years (mean=15.6)▫ N=9887 with geographic information▫ Nested within both household and neighborhood
(n=2400 tracts)
Clustering of Physical Activity (PA) and Obesity by Neighborhood
ICC
%
Effect Modification by Sex
Adjusted Odds Ratio (OR) , 95% Confidence Interval (CI)Outcomes: PA, Obesity/Overweight; Exposure: High Crime
Overall Among girls Among boys
Physical Activity0.86 (0.73, 1.00) 0.74 (0.59, 0.92) 0.98 (0.80, 1.21)
Obesity/Overweight1.11 (1.04, 1.31) 1.27 (1.02 , 1.58) 1.11 (0.94, 1.31)
Adjusted for: age, education, race, Poverty Income Ratio, HEI score, survey year, years living in neighborhood, adult PA and BMI, urban-rural status
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Neighborhood Clustering of Allostatic Load and Individual Biomarkers
ICC (%
)
Impact of Neighborhood Cumulative Risk on Allostatic Load (AL)
AL: ≥ 2 biomarkers; > 1 S.D. OR (95% CI) aOR *(95% CI)
Cumulative risk Low to none (0) 1.00 1.00
Medium (1-2) 1.16 (1.16, 1.17) 1.09 (1.08, 1.09)
High (3-4) 1.37 (1.36, 1.37) 1.28 (1.27, 1.30)
Extremely high ( > 4) 1.84 (1.83, 1.85) 1.69 (1.68, 1.70)
ICC (%) 6.23 (empty) to 2.71 2.09Median Odds Ratio (MOR) 2.20 (empty) to 1.47 1.42Explained group level variance 65.0% 15.4%
* Adjusted for sex, age, race/ethnicity, family poverty income ratio (PIR), household adult AL score and education, marital status, years in neighborhood, HEI, physical activity, ICE, urbanicity, survey year.
NSPAC (Neighborhood and Stress Physiology Among Children) Study
• Sample of 120 African American children▫ Ages 5-16▫ Recruited public schools, clinics, local partners in
New Orleans, Louisiana, U.S. ▫ January 2012 – July 2013▫ Age- and Katrina-exposure matched 1:1▫ 32.5% obese or overweight
• Georeferenced to census tract level▫ 51 tracts (“neighborhoods”)▫ Buffers around the home (500, 1000, 2000 meters)
Impact of Witnessed Violence
Adjusted B overall = -0.20, p < 0.05
Adjusted B girls = -0.30, p < 0.05
Adjusted B boys = -0.13, n.s.
Objective Neighborhood Effects
Community Violence and Telomeres, cortisol and behavior Neighborhood exposure - Total Crime per 1000 Domestic Violence Calls
per 1000 Outcomes
Beta (SE) P-value Beta (SE) P-value
Telomere length (T/S ratio)
-1.43 (0.39) 0.0003 -1.11 (0.37) 0.002
Cortisol recovery
0.22 (0.23) 0.081 0.10 (0.004) 0.043
Aggression and impulsivity
15.98 (4.37) 0.032 1.89 (0.90) 0.054
Theall et al. in preparation
What about overweight/obesity? Homicide Rate and BMI and WC
Rho = 0.205; R2 = 5.1% Rho = 0.179; R2 = 3.5%
Conceptual Model – Neighborhoods & Obesity
Neighborhood Conditions
Family/Household Conditions
Biologic Stress / Telomere Length
Obesity / Overweight
Biologic Stress / Telomere Length
Telomere Length and Obesity
• Inconsistent association in children but recent, larger studies:▫ Al-Attas et al. (2010), Arab youth Boys: TL shorter in obese vs non-obese and R2= 86% SBP Girls: No differences by obesity and R2= 24% WC
▫ Buxton et al. (2011), French youth Obese children had a mean LTL 23.9% shorter than non-
obese ▫ García-Calzón et al. (2014), Spanish obese/overweight
youth Significant increase in TL following weight loss; higher
baseline TL higher decrease in body weight in boys
Adolescent Intervention & Impact on TL
Garcia-Calzon et al, 2014
TL and BMI and WC in NSPAC
Rho = -0.371; R2 = 13.8% Rho = -0.459; R2 = 21.1%
Mediation Model – Homicide and BMI
Homicide Rate
Telomere Length
BMI
Direct effect = 0.3939 (0.136); t=2.89, p=0.005
* Indirect effect = -0.062 (Boot SE=0.0.037), Boot CI = -0.1644, -0.0072
* *
Moderation Model – Homicide and BMI
Homicide Rate
Telomere Length
BMI
* Moderating effect TL * Homicide Rate z=1.93, p=0.053
*
Moderation Model – Homicide and BMI
R2 = 20.0%; z=7.39, p = 0.011 R2 = 2.6%; z=2.19, p = 0.143
Among those with higher TL Among those with lower TL
Implications• TL maybe a biological “scar” of early adversity, including
neighborhood exposures▫ Multiple pathways and black boxes!
• Understanding the factors the influence TL may provide new avenues for intervention/prevention
• Monitoring TL may provide insight into the biological, rather than symptomatic, impact of interventions
Collaborators Thank you • Stacy Drury• Elizabeth Shirtcliff• John Carlson
• Richard Scribner• Claire Sterk• Charlie Zeanah • Steve Nelson• Patricia Molina
QUESTIONS?