Toxic Stress & the Developing Brain: Risk & Resilience Rosalind J. Wright, MD, MPH

Transcription

1 Toxic Stress & the Developing Brain: Risk & Resilience Rosalind J. Wright, MD, MPH Horace W. Goldsmith Professor Dean for Translational Biomedical Sciences Department of Pediatrics & Department of Environmental Medicine & Public Health Icahn School of Medicine at Mount Sinai

2 Socially Toxic Environments Coined by James Garbarino (1970s) Violence Poverty Economic hardships Racism/discrimination Social Pollutants Social toxins are as detrimental as chemical/physical toxins to children s development 1 Effects begin prenatally Wright RJ. Moving towards making social toxins mainstream in children s environmental health. Current Opinion in Pediatrics. 2009;21: Kingston D: The effects of prenatal and postpartum maternal psychological distress on child development: a systematic review. The Centre for Child, Family and Community Research: Edmonton, Alberta; 2011.

3 Key Regulatory Systems Autonomic Function HPA Axis Function Immune Function Oxidant- Antioxidant Balance OPTIMAL BALANCE = HEALTH Stress physiology organized around 2 systems SAM & HPA Interact with immune function & oxidant balance

4 Stress Microbes Smoke Air pollution Autonomic Function HPA Axis Function Immune Function Oxidant- Antioxidant Balance

5 Prenatal Maternal Stress/Trauma Potential Mechanism Enhanced Oxidative Stress

6 PRogramming of Intergenerational Stress Mechanisms (PRISM) Study Pregnancy cohort to study long term health consequences of stress starting in pregnancy and maternal caregiving on child development Dual site study Boston & NY N ~ 800 to date NHLBI, NICHD, NIEHS, ECHO The same soul governs the two bodies and the desires and fears and sorrows are common. Leonardo da Vinci 6

7 Cumulative Stress Domains Financial strain Racism/discrimination Relationships Community/interpersonal violence Other negative life events (housing, landlords, fear of eviction, etc.) Life course vs. current

8 Chemical and Non-chemical Stressors Impact Brain Function in Multiple Domains Metals Ambient Air Pollution Stress

9 Infant Temperament Infant temperament Later personality & social development Risk for emotional & behavioral problems Infant Negative Affectivity (NA) Heritable trait tendency to experience negative feelings (e.g., worry, anxiety, fear, depression, self-criticism) Individuals higher in NA tend to experience negative emotions more frequently compared to those lower in NA Common underlying factor contributing to both anxiety and mood disorders Reflects a stable personality trait of emotional instability and elevated baseline sympathetic activity

10 Infant Negative Affectivity (NA) Stable Over Lifecourse Infant NA Childhood NA Adult Neuroticism

11 Infant Neurobehavior Assessment 191-item Infant Behavior Questionnaire-Revised (IBQ-R) Mothers rated frequency child engaged in specific day-to-day behaviors in prior week using 7-point scale (1-never, 7-always) 14 Subscales e.g., Activity Level, Fear, Approach, Duration of Orienting, Distress to Limitations, Sadness, Vocal Reactivity, Falling Reactivity 3 Overarching Factors (confirmed using factor analysis) Extraversion Orienting/Regulation Negative Affectivity 11

12 Maternal Lifetime Stress/Trauma & Infant Negative Affectivity Bosquet-Enlow M, et al., Infancy 2017 (in press)

13 Effect Modified by Mother s Cortisol Level in Pregnancy Bosquet-Enlow M, et al., Infancy 2017 (in press)

14 Summary Distress to limitations distress to frustration or confinement Increased maternal trauma associated with greater infant distress to limitations particularly if exposed to higher cortisol in utero Falling Reactivity infant stress regulatory capacity Association between maternal trauma & infant rate of recovery from arousal (Falling Reactivity) seen only when prenatal cortisol exposure considered Maternal trauma associated with slower recovery from arousal among infants exposed to higher prenatal cortisol Maternal trauma associated with faster recovery from arousal among infants exposed to lower prenatal cortisol

15 Beneficial effect of fatty acids and vitamin E? Polyunsaturated Fatty Acids (Omegas 3 and 6) Anti-inflammatory properties n3:n6 ratio beneficial for brain development Vitamin E Reduce toxin-induced oxidative stress in the placenta and brain Protective against neuronal damage in presence of oxidative stress Ameliorate the effects of toxins known to influence neurodevelopment Tobacco smoke, methyl-mercury What about stress in pregnancy? 15

16 Prenatal Stress AP Smoking Maternal Diet Antioxidants (Vitamin E) Disrupted Airway Development Enhanced Oxidative Stress Anti-inflammatory Nutrients (PUFAs) Disrupted Epithelia Development

17 Early Childhood behavior Questionnaire- Very Short form (ECBQ-VS) 36-item ECBQ-VS Mothers rated frequency child engaged in specific day-to-day behaviors in prior 2 weeks using 7-point scale (1-never, 7-always) Age 30 months 3 Overarching Factors (confirmed using factor analysis) Surgency/Extraversion Effortful Control Negative Affectivity 17

18 Prenatal Stress & NA: Effects Modified by Diet in Pregnancy Submitted manuscript

19 Summary Maternal exposure to increasing stress over pregnancy was associated with higher child negative affectivity at 30 months Association between increased prenatal stress and increased child NA was stronger among children of mothers with lower prenatal intakes of antioxidants (Zn, Se and Vitamins A & C) Statistically significant interaction terms First longitudinal study showing modification of prenatal stress effects on child temperament by prenatal antioxidant intakes

20 During early childhood human stress response systems are under strong social regulation Sensitive, responsive, supportive care buffers young children from Experiencing disruption of these stress response systems As quality of care decreases, young children become more Stress vulnerable

21 Lab Stressor Caregiving Sensitivity Negative Affect HPA Axis ANS Activity SNS PNS

22 Maternal Sensitivity and Infant Autonomic Response More distressed Insenstive Sensitive Greater sympathetic (adrenalin) response Bosquet Enlow, et al Early Human Development, 2014, 99:

23 Maternal Sensitivity and Infant Neuroendocrine Response Insenstive Sensitive Increased cortisol production Bosquet Enlow, et al Early Human Development, 2014, 99:

24 Summary Maternal sensitivity buffers negative affect Maternal sensitivity buffers activation of ANS and HPA axis despite distress Needs to examine sex-specific effects Need for caregiving interventions in infancy/early childhood

25 Lifecourse strategy for neurodevelopment Chronic ND risk Adulthood No intervention Late intervention less impactful Late intervention Mother & infant Childhood Earlier intervention improves functional capacity & responses to new challenges Early intervention Most impactful Fixed genetic contributions to risk is small Life course Plasticity Inadequate response to new challenges Gluckman, Hanson, Cooper et al New Engl J Med 2008; 359: Hanson M, Godfrey K et al Prog Biophys Molec Biol 2011; 106:

26 Negative Affectivity and Later Neurodevelopmental Outcomes Elucidating factors that shape early NA may inform our understanding of the earliest origins of mental health risk and resilience, and a range of other neurodevelopmental outcomes. Internalizing Symptoms Externalizing Symptoms Infant Temperament Negative Affectivity Poor Executive Function Diminished Social Responsivene ss

27 Looking ahead.. It is easier to build strong children than to repair broken men. Frederick Douglas

28 Co-investigators Krisitn Bernard (SB) Michelle Bosquet-Enlow (HMS) Joel Schwartz (HSPH) Brent Coull (HSPH) John Staudenmayer (UMass) Thomas Ritz (SMU) Robert Wright (ISMMS) Chris Gennings (ISMMS) Pre/Postdoctoral Students Michelle Sternthal Kelly Brunst Hannah Schreier Shakira Franco Suglia Yu-Ming Ni Lianna Lipton Katrina Devick Funding NIEHS NHLBI NIMHD NIMH NICHD Leaves of Grass Foundation ECHO