PEERING INTO THE BLACK BOX: Understanding Toxic Stress and the Link Between Childhood Adversity and Poor Health

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1 PEERING INTO THE BLACK BOX: Understanding Toxic Stress and the Link Between Childhood Adversity and Poor Health? Andrew Garner, M.D., Ph.D., F.A.A.P. University Hospitals Medical Practices, and Associate Clinical Professor of Pediatrics, Case Western Reserve School of Medicine, and Chair, AAP Leadership Workgroup on Early Brain and Child Development

2 My 2 Objectives For Today Explain how toxic stress mediates the relationship between childhood adversity and poor adult health Discuss the public health implications and potentially lifelong consequences of toxic stress

3 Critical Concept #1 Childhood Adversity has Lifelong Consequences. Significant adversity in childhood is strongly associated with unhealthy lifestyles and poor health decades later.

4 ACE Categories Women Men Total Abuse (n=9,367) (n=7,970) (17,337) Emotional 13.1% 7.6% 10.6% Physical 27.0% 29.9% 28.3% Sexual 24.7% 16.0% 20.7% Household Dysfunction Mother Treated Violently 13.7% 11.5% 12.7% Household Substance Abuse 29.5% 23.8% 26.9% Household Mental Illness 23.3% 14.8% 19.4% Parental Separation or Divorce 24.5% 21.8% 23.3% Incarcerated Household Member 5.2% 4.1% 4.7% Neglect* Emotional 16.7% 12.4% 14.8% Physical 9.2% 10.7% 9.9% 1:4! 1:4! * Wave 2 data only (n=8,667) Data from

ACEs Impact Multiple Outcomes Smoking Alcoholism Promiscuity High Perceived Risk of HIV Obesity Risk Factors for Common Diseases Poor Perceived Health IV Drugs Multiple Somatic Symptoms Cancer

5 ACEs Impact Multiple Outcomes Smoking Alcoholism Promiscuity High Perceived Risk of HIV Obesity Risk Factors for Common Diseases Poor Perceived Health IV Drugs Multiple Somatic Symptoms Cancer Skeletal Fractures Sexually Transmitted Diseases Illicit Drugs Relationship Problems High perceived stress Prevalent Diseases Difficulty in job performance General Health and Social Functioning Liver Disease Chronic Lung Disease Ischemic Heart Disease ACEs Married to an Alcoholic Sexual Health Teen Paternity Teen Pregnancy Depression Mental Health Anxiety Unintended Pregnancy Sexual Dissatisfaction Fetal Death Poor Self- Rated Health Hallucinations Sleep Disturbances Memory Disturbances Panic Reactions Poor Anger Control Early Age of First Intercourse

6 Linking Childhood Experiences and Adult Outcomes Childhood Adversity Poor Adult Outcomes?

7 Defining Adversity or Stress How do you define/measure adversity? Huge individual variability Perception of adversity or stress (subjective) Reaction to adversity or stress (objective) National Scientific Council on the Developing Child (Dr. Jack Shonkoff and colleagues) Positive Stress Tolerable Stress Toxic Stress Based on the REACTION (objective physiologic responses)

8 Defining Adversity or Stress Positive Stress Brief, infrequent, mild to moderate intensity Most normative childhood stress Inability of the 15 month old to express their desires The 2 year old who stumbles while running Beginning school or daycare The big project in middle school Social-emotional buffers allow a return to baseline (responding to non-verbal clues, consolation, reassurance, assistance in planning) Builds motivation and resiliency Positive Stress is NOT the ABSENCE of stress

9 Defining Adversity or Stress Toxic Stress Long lasting, frequent, or strong intensity More extreme precipitants of childhood stress (ACEs) Physical, sexual, emotional abuse Physical, emotional neglect Household dysfunction Insufficient social-emotional buffering (Deficient levels of emotion coaching, re-processing, reassurance and support) Potentially permanent changes and long-term effects Epigenetics (there are life long / intergenerational changes in how the genetic program is turned ON or OFF) Brain architecture (the mediators of stress impact upon the mechanisms of brain development / connectivity)

10 Critical Concept #2 Epigenetics: Which genes are turned on/off, when, and where Ecology (environment/experience) influences how the genetic blueprint is read and utilized Ecological effects at the molecular level Many epigenetic changes in gene expression are stress-induced Genes may load the gun, but the environment pulls the trigger Epigenetics: NOT your parents genome!

11 Impact of Maternal Stress MATERNAL TOXIC STRESS NEWBORN HPA reactivity and salivary cortisol levels methylation of the FETAL glucocorticoid (GC) receptor gene brain expression of the GC receptor

12 Critical Concept #3 Developmental Neuroscience: Brain Architecture is experience dependent (individual connections or synapses and complex circuits of connections or pathways are both dependent upon activity) Ecology (environment/experience) influences how brain architecture is formed and remodeled (plasticity) Diminishing cellular plasticity limits remediation Early childhood adversity -> vicious cycle of stress (differential maturation) Early experiences lead to potentially permanent alterations in brain architecture and functioning

13 Two Types of Plasticity Synaptic Plasticity Variation in the STRENGTH of individual connections from a whisper to a shout Lifelong (how old dogs learn new tricks) Cellular Plasticity Variations in the NUMBER (or COUNT) of connections from one person shouting to a stadium shouting Declines dramatically with age (waning by age 5)

14 Adapted from Ken Winters, Ph.D. Differential Brain Maturation Prefrontal Cortex Amygdala (AKA The Brake) (AKA The Gas Pedal) Cold Cognition Hot Cognition Judgmental Emotional Reflective Reactive Calculating Impulsive Think about it Just do it Biological maturity by 24 Biological maturity by 18

15 Impact of Childhood Stress CHILDHOOD TOXIC STRESS Hyper-responsive stress response; calm/coping Chronic fight or flight; cortisol / norepinephrine Changes in Brain Architecture

16 SUMMARY What is Toxic Stress? A physiologic stress response that is excessive or prolonged (reflects an inability to turn it off ) Results in potentially permanent changes in: Gene expression (epigenetics) Brain development (neuroscience) Behavior (allostasis)

17 The BIG Questions are Since TOXIC STRESS is a mediator between ACE exposure and poor adult outcomes, it raises the following BIG questions: Are there ways to: treat, YES! mitigate, and/or immunize against the effects of toxic stress? If so, is there a mismatch between: what we KNOW and what we actually DO? ALL are necessary NONE are sufficient!!

18 Public Health Implications What we DO: 95% of the trillions of dollars that we spend on health is on treatment and NOT prevention What we KNOW: That 70% of early deaths are preventable, with The majority (40% overall) due to behavioral patterns that lead to chronic disease. Is this Behavioral Allostasis due to toxic stress? McGinnis, Williams-Russo and Knickman, 2002

19 Proximal Causes of Death: Chronic Disease Acute causes of death are the exception, not the rule

20 Distal Causes of Death: Unhealthy Lifestyles If these unhealthy lifestyles are manifestations of behavioral allostasis, a FUNDAMENTAL cause of death is TOXIC STRESS!

21 By 2030, 90% of the morbidity in high income countries will be due to NCDs (Non- Communicable Diseases NCDs are related to unhealthy behaviors (overeating/inactivity, smoking, alcohol, and substance abuse)

22 How/When do those automatic processes form in the first place!?

23 Critical Concept #4 Do we continue to treat disease, the unhealthy lifestyles that lead to disease, or the TOXIC STRESS that leads to the adoption of unhealthy lifestyles??

24 SUMMARY Why should I care about Toxic Stress? Toxic stress is a MEDIATOR between early childhood adversity and less than optimal outcomes in learning, behavior and health Understanding the BIOLOGY underlying these well established associations opens up new opportunities for primary prevention and early intervention

25 Linking Childhood Experiences and Adult Outcomes Childhood Adversity Poor Adult Outcomes Toxic Stress Epigenetic Modifications Disruptions in Brain Architecture Improve caregiver/community capacity to prevent or minimize toxic stress (e.g. efforts to promote the safe, stable and nurturing relationships that turn off the physiologic stress response) Behavioral Allostasis Maladaptive behaviors Non-communicable Diseases Improve caregiver/community capacity to promote healthy, adaptive coping skills (e.g. - efforts to encourage rudimentary but foundational SE, language, and cognitive skills )

26 CONCLUSION: It is easier to build strong children than to repair broken men. Frederick Douglass

27 REFERENCES Garner AS, et al. (2012) Early childhood adversity, toxic stress, and the role of the pediatrician: translating developmental science into lifelong health. Pediatrics 129(1):e Shonkoff JP, et al. (2012) The Lifelong Effects of Early Childhood Adversity and Toxic Stress. Pediatrics 129(1):e Blair C et al. (2011) Salivary cortisol mediates effects of poverty and parenting on executive functions in early childhood. Child Dev 82(6): Marteau TM, Hollands GJ, Fletcher PC (2012) Changing human behavior to prevent disease: the importance of targeting automatic processes. Science 337: Bygbjerg IC (2012) Double burden of noncommunicable and infectious diseases in developing countries. Science 337: Mokdad AH, Marks JS, Stroup DF, Gerberding JL (2004) Actual causes of death in the United States, JAMA 291: Hoyert DL, et al. (2006) Deaths: Final data for National Vital Statistics Reports 54:

28 REFERENCES McGinnis JM, Williams-Russo P, Knickman JR (2002) The case for more active policy attention to health promotion. Health Aff (Millwood) 21(2): Luby JL, et al. (2012) Maternal support in early childhood predicts larger hippocampal volumes at school age. PNAS U S A 109(8): Walker, et al. (2011) Early Childhood Stimulation Benefits Adult Competence and Reduces Violent Behavior. Pediatrics 127: Anda RF, et al. (2006) The enduring effects of abuse and related adverse experiences in childhood. A convergence of evidence from neurobiology and epidemiology. Eur Arch Psychiatry Clin Neurosci 256: Felitti VJ, et al. (1998) Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults. The Adverse Childhood Experiences (ACE) Study. Am J Prev Med 14(4): Odgers CL and Jaffee SR. (2013) Routine versus catastrophic influences on the developing child. Annu Rev Public Health 34:29-48.

29 Developmental Origins of Health and Disease COSTS OF CARE Hansen and Gluckman, Am J Clin Nutr doi /ajcn

30 Social-Emotional Safety Nets A Public Health Approach to Toxic Stress Universal Primary Preventions Anticipatory guidance Consistent messaging (CTC) No identification No stigma Ceiling effects = Limited evidence base Targeted Interventions (for those at risk ) Nursing home visits (NFP) Parenting programs (Legacy/PPP) Early Intervention (Ideally!) Less ceiling=more evidence Requires screening Issues with stigma Evidence-Based Treatments (for the symptomatic) PCIT; TB-CBT; Pharmacotx Treatment works! Screening / stigma / access

31 WHAT are we DOING?! Universal Primary Preventions Bright Futures Connected Kids / HS - NCH NFP / VIP / PFR / COS Relationships as a vital sign Decrease Stress/Build Skills Targeted Interventions Screening for risks Assess the ecology (SEEK/cACE) Refer to/advocate for EBI Collaborating/Developing EBI ID Risks/Provide EBI Evidence-Based Treatments Screening for diagnoses Common factors approach Refer for/advocate for EBT Collaborating/Developing EBT ID Symptoms/Provide EBT

32 Developing a Shared VISION Toxic Stress It s like a snake! It s like a straw fan! It s like a tree trunk!

33 SE Buffers Toxic Stress Critical Concept #5 Protect the Brain Yin/Yang of Early Childhood: Build New Skills - Protect the Brain Maladaptive Skills Adaptive Skills - Build New Skills

Potential. Translating Developmental Science into Healthy Lives: Realizing the

Potential. Translating Developmental Science into Healthy Lives: Realizing the Translating Developmental Science into Healthy Lives: Realizing the Potential Andrew Garner, M.D., Ph.D., F.A.A.P. University Hospitals Medical Practices, and Associate Clinical Professor of Pediatrics,