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10 Categories of Adverse Childhood Experiences

Notes:

The term Adverse Childhood Experiences (ACEs) come from the landmark 1998 study conducted among more than 17,000 adult patients by the Centers for Disease Control and Prevention (CDC) and Kaiser Permanente. The term ACEs specifically refers to the 10 categories of adversities in three domains experienced by age 18 years that were evaluated in the study.

Abuse: Physical, emotional, or sexual
Neglect: Physical or emotional
Household challenges Growing up in a household with incarceration, mental illness, substance misuse or dependence, absence due to separation or divorce, or intimate partner violence (initially queried as violence towards the mother or stepmother)

One of the pieces that's really important is to recognize that the 10 ACEs identified in the landmark CDC/Kaiser Permanente study are certainly not the only risk factors for toxic stress. Other factors such as racial discrimination, separation from a parent or a caregiver for other reasons like deportation or migration or even a medical trauma may also be risk factors for toxic stress.

BACKGROUND NOTES:

Why we don’t add additional questions to the ACE screener or change the scoring to include other types of adversity:

When it comes to the traditional 10 ACEs, we have very large, robust population level data sets about relative risk of health conditions. So for example, with the traditional ACEs, we know that if an individual has four or more ACEs, their relative risk of, for example, ischemic heart disease is 220% (Felitti et al, 1998)

When you add in other risk factors for toxic stress like discrimination or like being a victim of violence in the community or elsewhere, we don't have the same reference ranges for those datasets. And that's why we score those differently. It's not that they aren't all risk factors for toxic stress, but when it comes to the integrity of the data around the relative

risk of different health conditions, we have to compare apples to apples. And that's why they're separated in that way.

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Prevalence of ACEs in California

Source: California Department of Public Health, Injury and Violence Prevention Branch (CDPH/IVPB), University of California, Davis, Violence Prevention Research Program, California Behavioral Risk Factor Surveillance System (BRFSS), 2011-2017.

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61.6% of US adults have ≥ 1 ACE �15.8% have ≥ 4 ACEs

62.3% Californians have ≥1 ACEs 16.3% have ≥ 4 ACEs

Sources: Merrick et al., Prevalence of adverse childhood experiences from the 2011-2014 Behavioral Risk Factor Surveillance System in 23 states. JAMA Pediatrics 2018; 172: 1038.; Merrick et al., Vital Signs: Estimated Proportion of Adult Health Problems Attributable to Adverse Childhood Experiences and Implications for Prevention — 25 States, 2015–2017. MMWR Morb Mortal Wkly Rep 2019;68:999-1005; Bethell et al., Issue Brief: A national and across state profile on adverse childhood experiences among children and possibilities to heal and thrive. Johns Hopkins Bloomberg School of Public Health, October 2017.

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ACEs Dramatically Increase Risk for �at least 9 of the 10 Leading Causes of Death in the U.S.

Source of causes of death: CDC, 2017; Sources of odds ratios: Hughes et al., 2017 for 1, 2, 4, 7, 10; Petrucelli et al., 2019 for 3 (injuries with fracture), 5; Center for Youth Wellness, 2014 for 6 (Alzheimer’s or dementia); Center for Youth Wellness, 2014 and Merrick et al., 2019 for 9.

	Leading Causes of Death in the U.S., 2017	Odds Ratios for ≥ 4 ACEs (relative to no ACEs)
1	Heart disease	2.1
2	Cancer	2.3
3	Accidents (unintentional injuries)	2.6
4	Chronic lower respiratory disease	3.1
5	Stroke	2.0
6	Alzheimer’s disease or dementia	11.2
7	Diabetes	1.4
8	Influenza and pneumonia	Unknown
9	Kidney disease	1.7
10	Suicide (attempts)	37.5

A consensus of scientific research demonstrates that cumulative adversity, especially when experienced during critical and sensitive periods of development, is a root cause to some of the most harmful, persistent, and expensive health challenges facing our state and nation, including at least 9 of the 10 leading causes of death in the United States.

Full citations:

Hughes K, Bellis MA, Hardcastle KA, et al. The effect of multiple adverse childhood experiences on health: a systematic review and meta-analysis. The Lancet Public Health 2017; 2: e356–66.

Petruccelli K, Davis J, Berman T. Adverse childhood experiences and associated health outcomes: A systematic review and meta-analysis. Child Abuse & Neglect 2019; 97: 104127

Center for Youth Wellness. A hidden crisis: Findings on Adverse Childhood Experiences in California. 2014.

Merrick MT, Ford DC, Ports KA, et al. Vital Signs: Estimated Proportion of Adult Health Problems Attributable to Adverse Childhood Experiences and Implications for Prevention—25 States, 2015–2017. MMWR Morb Mortal Wkly Rep 2019; 68. DOI:10.15585/mmwr.mm6844e1.

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5

ACE-Associated Health Conditions – Pediatrics

*Odds ratio represents at least one ACE, but also includes other adversities

**Prevalence ratio represents at least one ACE, but also includes other adversities

For more details, see the ACE Screening Workflows, Risk Assessment and Treatment Algorithms, and ACE-Associated Health Conditions at acesaware.org/aahcs

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6

ACE-Associated Health Conditions – Adults

Odds ratios compare outcomes in individuals with > 4 ACEs to those with 0 ACEs, except where specified

For more details, see the ACE Screening Workflows, Risk Assessment and Treatment Algorithms, and ACE-Associated Health Conditions at acesaware.org/aahcs

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Toxic Stress Response

A consensus of scientific evidence demonstrates that high doses of cumulative adversity experienced during critical and sensitive periods of early life development, without the buffering protections of safe, stable and nurturing relationships and environments, can lead to long-term disruptions of brain development, immune and hormonal systems and genetic regulatory mechanisms—a condition now known as the “toxic stress response.”

Sources: Shonkoff JP, Garner AS, Dobbins MI, et al. The lifelong effects of early childhood adversity and toxic stress. Pediatrics 2012; 129: e232–46. DOI: 10.1542/peds.2011-2663.

Johnson SB, Riley AW, Granger DA, Riis J. The science of early life toxic stress for pediatric practice and advocacy. Pediatrics 2013; 131: 319–27. DOI: 10.1542/peds.2012-0469.

Garner AS, Shonkoff JP, Committee on Psychosocial Aspects of Child and Family Health, Committee on Early Childhood, Adoption, and Dependent Care, Section on Developmental and Behavioral Pediatrics, et al. Early childhood adversity, toxic stress, and the role of the pediatrician: translating developmental science into lifelong health. Pediatrics 2012; 129: e224–31. DOI: 10.1542/peds.2011-2662.

Bucci M, Marques SS, Oh D, Harris NB. Toxic Stress in Children and Adolescents. Advances in Pediatrics 2016; 63: 403–28. DOI: 10.1016/j.yapd.2016.04.002.

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The Toxic Stress Response

“prolonged activation of the stress response systems that can disrupt the development of brain architecture and other organ systems, and increase the risk for stress-related disease and cognitive impairment, well into the adult years…”

Source: National Academies of Sciences, Engineering, and Medicine. Vibrant and healthy kids: Aligning science, practice, and policy to advance health equity. Washington, DC: National Academies Press, 2019.

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Risk Factors for Toxic Stress

A circumstance, exposure, or condition with documented associations with increased likelihood or susceptibility of development of the toxic stress response.

In addition to ACEs, other risk factors for toxic stress include poverty, exposure to discrimination, and exposure to the atrocities of war.

Source: Bhushan D, Kotz K, McCall J, Wirtz S, Gilgoff R, Dube SR, Powers C, Olson-Morgan J, Galeste M, Patterson K, Harris L, Mills A, Bethell C, Burke Harris N, Office of the California Surgeon General. Roadmap for Resilience: The California Surgeon General’s Report on Adverse Childhood Experiences, Toxic Stress, and Health. Office of the California Surgeon General, 2020. DOI: 10.48019/PEAM8812. (p. xxiv)

ACEs, SDOH, other risk factors for toxic stress

Social and structural inequities disproportionately concentrate ACEs, toxic stress,

their precursors, and their consequences in racially, socially, and economically

marginalized communities. Such contexts can exacerbate the impacts of ACEs and

toxic stress and reduce access to buffering resources.

Please see Core Training Criteria for additional information.

Notes

Social determinants of health include but are not limited to the 10 ACEs from the landmark study.

SDOH issues should be addressed with appropriate services, but are not used in calculating the ACE score because the strengths of association between SDOHs and health outcomes have not been standardized in the ways that ACEs have been. (SG Report p. 242)

Recognizing these additional risks is important since they often co-occur with ACEs, contribute to their prevalence, and can exacerbate their impacts. It is also crucial to understand and address the ways in which these factors may compound the cumulative dose of adversity and reduce caregivers’ ability to provide safe, stable, and nurturing relationships and environments, particularly given the disproportionate burden of ACEs in marginalized communities.

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Additional Adversities are Risk Factors for Toxic Stress

“Social determinants of health are conditions in the environments in which people live, learn, work, play, worship, and age that affect a wide range of health, functioning, and quality-of-life outcomes and risks. The social determinants of health are: education, employment, health systems and services, housing, income and wealth, the physical environment, public safety, the social environment (including structures, institutions, and policies), and transportation”*

While validated odds ratios are available in large, population-based studies using the 10 standardized ACE criteria, the strengths of association between other experiences/social determinants on health and health outcomes have not been similarly standardized.

Source: *Center on the Developing Child at Harvard University, n.d. cited in National Academies of Sciences, Engineering, and Medicine. Vibrant and healthy kids: Aligning science, practice, and policy to advance health equity. Washington, DC: National Academies Press, 2019.

Solar O, Irwin A. A conceptual framework for action on the social determinants of health. Geneva: World Health Organization, 2010.

Please see Core Training Criteria for additional information.

Notes

Social determinants of health include but are not limited to the 10 ACEs from the landmark study.

SDOH issues should be addressed with appropriate services, but are not used in calculating the ACE score because the strengths of association between SDOHs and health outcomes have not been standardized in the ways that ACEs have been. (SG Report p. 242)

Recognizing these additional risks is important since they often co-occur with ACEs, contribute to their prevalence, and can exacerbate their impacts. It is also crucial to understand and address the ways in which these factors may compound the cumulative dose of adversity and reduce caregivers’ ability to provide safe, stable, and nurturing relationships and environments, particularly given the disproportionate burden of ACEs in marginalized communities.

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Social Determinants of Health (SDOH)

“Social Determinants of Health (SDOH) are conditions in the environments in which people live, learn, work, play, worship, and age that affect a wide range of health, functioning, and quality-of-life outcomes and risks.

SDOH include:

Education
Employment
Health systems and services
Housing
Income and wealth
Physical environment
Public safety
Social environment (including

structures, institutions, and policies),

and transportation”*

Source: The Catalyst Center Supplemental Training

*Center on the Developing Child at Harvard University, n.d. cited in NASEM, 2019

Bhushan D, Kotz K, McCall J, Wirtz S, Gilgoff R, Dube SR, Powers C, Olson-Morgan J, Galeste M, Patterson K, Harris L, Mills A, Bethell C, Burke Harris N. Office of the California Surgeon General. Roadmap for Resilience: The California Surgeon General's Report on Adverse Childhood Experiences, Toxic Stress, and Health. Office of the California Surgeon General, 2020. DOI: 10.48019/PEAM8812

Social Determinants Of Health:

Foster unmet social needs that often co-occur with ACEs
Contribute to the prevalence of ACEs
Can exacerbate the impact of ACEs and increase the likelihood they will lead to toxic stress
Some may directly lead to toxic stress
May reduce availability of safe, stable, and nurturing relationships and environments due to cumulative dose of adversity

SDOH, ACEs, and Toxic Stress

Live

Learn

Work

Play

Worship

Age

Let’s take a moment to define the Social Determinants of Health and how these additional adversities are risk factors for toxic stress.

According to the Center for the Developing Child at Harvard University, “Social determinants of health are conditions in the environments in which people live, learn, work, play, worship, and age that affect a wide range of health, functioning, and quality-of-life outcomes and risks. The social determinants of health are: education, employment, health systems and services, housing, income and wealth, the physical environment, public safety, the social environment (including structures, institutions, and policies), and transportation”*
While validated odds ratios are available in large, population-based studies using the 10 standardized ACE criteria, the strengths of association between other experiences/social determinants of health and health outcomes have not been similarly standardized.
Recognizing these additional risks is important since they often co-occur with ACEs, contribute to their prevalence, and can exacerbate their impacts. It is also crucial to understand and address the ways in which these factors may compound the cumulative dose of adversity and reduce caregivers’ ability to provide safe, stable, and nurturing relationships and environments, particularly given the disproportionate burden of ACEs in systemically marginalized communities.

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Definition of Trauma

" Individual trauma results from an event, series of events, or set of circumstances that is experienced by an individual as physically or emotionally harmful or life threatening and that has lasting adverse effects on the individual’s functioning and mental, physical, social, emotional, or spiritual well-being.”

Substance Abuse and Mental Health Services Administration. SAMHSA’s Concept of Trauma and Guidance for a Trauma-Informed Approach. HHS Publication No. (SMA) 14-4884. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2014. https://ncsacw.samhsa.gov/userfiles/files/SAMHSA_Trauma.pdf

SAMHSA expanded definition (from SAMHSA’s Tip 57: A TREATMENT IMPROVEMENT PROTOCOL Trauma-Informed Care in Behavioral Health Services (https://www.ncbi.nlm.nih.gov/books/NBK207191/ ):

What Is Trauma? According to SAMHSA’s Trauma and Justice Strategic Initiative, “trauma results from an event, series of events, or set of circumstances that is experienced by an individual as physically or emotionally harmful or threatening and that has lasting adverse effects on the individual’s functioning and physical, social, emotional, or spiritual well-being” (SAMHSA, 2012, p. 2). Trauma can affect people of every race, ethnicity, age, sexual orientation, gender, psychosocial background, and geographic region. A traumatic experience can be a single event, a series of events, and/or a chronic condition (e.g., childhood neglect, domestic violence). Traumas can affect individuals, families, groups, communities, specific cultures, and generations. It generally overwhelms an individual’s or community’s resources to cope, and it often ignites the “fight, flight, or freeze” reaction at the time of the event(s). It frequently produces a sense of fear, vulnerability, and helplessness. Often, traumatic events are unexpected. Individuals may experience the traumatic event directly, witness an event, feel threatened, or hear about an event that affects someone they know. Events may be humanmade, such as a mechanical error that causes a disaster, war, terrorism, sexual abuse, or violence, or they can be the products of nature (e.g., flooding, hurricanes, tornadoes). Trauma can occur at any age or developmental stage, and often, events that occur outside expected life stages are perceived as traumatic (e.g., a child dying before a parent, cancer as a teen, personal illness, job loss before retirement). It is not just the event itself that determines whether something is traumatic, but also the individual’s experience of the event. Two people may be exposed to the same event or series of events but experience and interpret these events in vastly different ways. Various biopsychosocial and cultural factors influence an individual’s immediate response and longterm reactions to trauma. For most, regardless of the severity of the trauma, the immediate or enduring effects of trauma are met with resilience—the ability to rise above the circumstances or to meet the challenges with fortitude. For some people, reactions to a traumatic event are temporary, whereas others have prolonged reactions that move from acute symptoms to more severe, prolonged, or enduring mental health consequences (e.g., posttraumatic stress and other anxiety disorders, substance use and mood disorders) and medical problems (e.g., arthritis, headaches, chronic pain). Others do not meet established criteria for posttraumatic stress or other mental disorders but encounter significant trauma-related symptoms or culturally expressed symptoms of trauma (e.g., somatization, in which psychological stress is expressed through physical concerns). For that reason, even if an individual does not meet diagnostic criteria for trauma-related disorders, it is important to recognize that trauma may still affect his or her life in significant ways. For more information on traumatic events, trauma characteristics, traumatic stress reactions, and factors that heighten or decrease the impact of trauma, see Part 1, Chapter 2, “Trauma Awareness,” and Part 1, Chapter 3, “Understanding the Impact of Trauma.”

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Rationale/Value of ACE Screening

Screening for ACEs and risk of toxic stress and providing targeted, evidence-based interventions for toxic stress can:

Improve efficacy and efficiency of health care;
Better support individual and family health and well-being;
Interrupt the intergenerational transmission of ACEs and toxic stress; and
Reduce long-term health costs.

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Rationale for Screening Children & Adults

For Children:

The National Academies of Sciences, Engineering, and Medicine (NASEM) recommends adoption of “screening for trauma and adversities early in life to increase the likelihood of early detection. This should include creating rapid response and referral systems that can quickly bring protective resources to bear when early-life adversities are detected, through the coordination of cross-sector expertise.”¹

For Adults:²

Allows for improved treatment of ACE-Associated Health Condition(s)
Offers opportunity to prevent vertical transmission of ACEs and toxic stress

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Rationale for Screening all Patients for ACEs

The high prevalence, health consequences, and costs of ACEs*
The impact of prevention and early intervention**
Enhances detection for those with non-neuropsychiatric conditions associated with ACEs and toxic stress***
Improves patient disclosure by normalizing and reducing perceived stigma****

Sources

* Merrick MT, Ford DC, Ports KA, Guinn AS, Chen J, Klevens J, et al. Vital Signs: Estimated Proportion of Adult Health Problems Attributable to Adverse Childhood Experiences and Implications for Prevention—25 States, 2015–2017. MMWR Morb Mortal Wkly Rep [Internet]. 2019 Nov 5 [cited 2019 Nov 6];68(44). Available from: http://www.cdc.gov/mmwr/volumes/68/wr/mm6844e1.htm?s_cid=mm6844e1_w

Rose G. Sick individuals and sick populations. Int J Epidemiol 19851432–38. Available from: https://pubmed.ncbi.nlm.nih.gov/3872850/

** Burke Harris N. The Deepest Well: Healing the Long-Term Effects of Childhood Adversity. Boston: Houghton Mifflin Harcourt, 2018.

Shonkoff JP, Garner AS, Dobbins MI, et al. The lifelong effects of early childhood adversity and toxic stress. Pediatrics 2012; 129: e232–46. DOI: 10.1542/peds.2011-2663.

Garner AS, Shonkoff JP, Committee on Psychosocial Aspects of Child and Family Health, Committee on Early Childhood, Adoption, and Dependent Care, Section on Developmental and Behavioral Pediatrics, et al. Early childhood adversity, toxic stress, and the role of the pediatrician: translating developmental science into lifelong health. Pediatrics 2012; 129: e224–31. DOI: 10.1542/peds.2011-2662.

National Research Council, National Academies. Vibrant and healthy kids: aligning science, practice, and policy to advance health equity. Washington, D.C.: National Academies Press, 2019. DOI: 10.17226/25466.

***Source of causes of death: CDC, 2017; Sources of odds ratios: Hughes et al., 2017 for 1, 2, 4, 7, 10; Petrucelli et al., 2019 for 3 (injuries with fracture), 5; Center for Youth Wellness, 2014 for 6 (Alzheimer’s or dementia); Center for Youth Wellness, 2014 and Merrick et al., 2019 for 9.

**** Shrivastava, Amresh, et al. "Clinical risk of stigma and discrimination of mental illnesses: Need for objective assessment and quantification." Indian journal of psychiatry 55.2 (2013): 178.

Stoto, Michael A., et al. "Public Health Screening Programs." Reducing the Odds: Preventing Perinatal Transmission of HIV In The United States. National Academies Press (US), 1999.

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ACE-Associated Health Conditions

ACE-Associated Health Conditions are health conditions that have empirical evidence showing associations between ACE exposure and the health outcome.

They include cardiovascular, pulmonary, immune, metabolic, mental health, and substance use conditions.*

While the relationship between ACEs and mental health outcomes is most commonly recognized, a recent meta-analysis demonstrates that the single greatest driver of ACE-associated health care costs is cardiovascular disease.**

Source: *Waehrer, Geetha M., et al. "Disease burden of adverse childhood experiences across 14 states." PLoS one 15.1 (2020): e0226134. Hughes, Karen, et al. "The effect of multiple adverse childhood experiences on health: a systematic review and meta-analysis." The Lancet Public Health 2.8 (2017): e356-e366.

**Bellis MA, Hughes K, Ford K, Ramos Rodriguez G, Sethi D, Passmore J. Life course health consequences and associated annual costs of adverse childhood experiences across Europe and North America: a systematic review and meta-analysis. Lancet Public Health 2019; 4: e517–28. DOI: 10.1016/S2468-2667(19)30145-8.

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Resilience

The ability to withstand or recover from stressors, and results from a combination of intrinsic factors and extrinsic factors (like safe, stable, and nurturing relationships with family members and others) as well as pre-disposing biological susceptibility.

Of note, with scientific advances in the understanding of the impact of stress on neuro-endocrine-immune and genetic regulatory health, we must advance our understanding of resilience as also having neuro-endocrine-immune and genetic regulatory domains.

Bhushan D, Kotz K, McCall J, Wirtz S, Gilgoff R, Dube SR, Powers C, Olson-Morgan J, Galeste M, Patterson K, Harris L, Mills A, Bethell C, Burke Harris N, Office of the California Surgeon General. Roadmap for Resilience: The California Surgeon General’s Report on Adverse Childhood Experiences, Toxic Stress, and Health. Office of the California Surgeon General, 2020. DOI: 10.48019/PEAM8812. p xxiv

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Protective Factors

Intrinsic Factors

Neurologic, endocrine, metabolic, immune, genetic, and epigenetic factors
Curiosity in learning
Ability to pay attention
Ability to regulate emotions

Extrinsic Factors

Buffering relationships
Supportive environments
Community resources

“Intrinsic or extrinsic conditions or attributes that mitigate risk for toxic stress”

Source: Bhushan D et al. Office of the California Surgeon General. Roadmap for Resilience: The California Surgeon General’s Report on Adverse Childhood Experiences, Toxic Stress, and Health. Office of the California Surgeon General, 2020. DOI: 10.48019/PEAM8812.

15

“Protective factors: intrinsic or extrinsic conditions or attributes that mitigate risk for toxic stress, such as curiosity and interest in learning, ability to pay attention and persist in completing tasks, ability to regulate emotions and behavior, feeling cared about and heard when things are hard, and having a sense of belonging in school and in the community, in addition to biological factors like differences in telomere length and the serotonin transporter gene”.36,41-46,87-95,97,604,665-667

“the risks associated with ACE exposure are modulated by multiple factors, such as biological susceptibility, which includes genetic material inherited from one’s parents, and protective factors, such as supportive relationships, environments, and community resources.36,41-46,87 “

■It is important to know that all of these are skills that can be learned. Every time you take a child to a museum, the library, to a park you are encouraging their curiosity in learning. When you stop and look at a caterpillar with them you are teaching them how to pay attention and focus. When they are crying and upset and you hug them, or rock them, or distract them with music or a toy you are teaching them skills to regulate their emotions.

While there are a number of validated, research-based tools to evaluate attachment and relational health, there are very few short, dynamic screens available for easy use in primary care clinical practice to screen for all protective factors. While tools such as the Protective Factors Survey may be useful, providers are also encouraged to have an open conversation with their patients about what the patient sees as their own personal strengths (or that of their child), and support systems - friends, relatives, community networks.

(If questions come up can further discuss Protective Factors Survey: https://friendsnrc.org/evaluation/protective-factors-survey/

Strength and Difficulties Questionnaire https://www.sdqinfo.org/a0.html

And Pediatric Symptom Checklist https://www.brightfutures.org/mentalhealth/pdf/professionals/ped_sympton_chklst.pdf

The factors listed are examples but not a complete list – and we have tools and strategies that can help address all of these for the children and adults we serve.

Bhushan D, Kotz K, McCall J, Wirtz S, Gilgoff R, Dube SR, Powers C, Olson-Morgan J, Galeste M, Patterson K, Harris L, Mills A, Bethell C, Burke Harris N, Office of the California Surgeon General. Roadmap for Resilience: The California Surgeon General’s Report on Adverse Childhood Experiences, Toxic Stress, and Health. Office of the California Surgeon General, 2020. DOI: 10.48019/PEAM8812.

36 Cheng TL, Johnson SB, Goodman E. Breaking the intergenerational cycle of disadvantage: The three generation approach. Pediatrics 2016; 137(6): e20152467.

41. Bethell C, Jones J, Gombojav N, Linkenbach J, Sege R. Positive Childhood Experiences and adult mental and relational health in a statewide sample: Associations across Adverse Childhood Experiences levels. JAMA Pediatrics 2019: e193007.

42. Sege RD, Harper Browne C. Responding to ACEs with HOPE: Health Outcomes from Positive Experiences. Academic Pediatrics 2017; 17(7): S79-S85.

43. Crandall A, Miller JR, Cheung A, et al. ACEs and counter-ACEs: How positive and negative childhood experiences influence adult health. Child Abuse & Neglect 2019; 96: 104089.

44. Bellis MA, Hardcastle K, Ford K, et al. Does continuous trusted adult support in childhood impart life-course resilience against Adverse Childhood Experiences—a retrospective study on adult health-harming behaviours and mental well-being. BMC Psychiatry 2017; 17(1): 110.

45. Bellis MA, Hughes K, Ford K, et al. Adverse Childhood Experiences and sources of childhood resilience: A retrospective study of their combined relationships with child health and educational attendance. BMC Public Health 2018; 18(792).

46. Schofield TJ, Lee RD, Merrick MT. Safe, stable, nurturing relationships as a moderator of intergenerational continuity of child maltreatment: A meta-analysis. Journal of Adolescent Health 2013; 53(4, Suppl): S32-8.

665. Schaefer LM, Howell KH, Schwartz LE, Bottomley JS, Crossnine CB. A concurrent examination of protective factors associated with resilience and posttraumatic growth following childhood victimization. Child Abuse & Neglect 2018; 85: 17-27.

666. Sege R, Bethell C, Linkenbach J, Jones JA, Klika B, Pecora PJ. Balancing Adverse Childhood Experiences with HOPE: New insights into the role of positive experience on child and family development. Boston: Medical Foundation, 2017.

667. Agenor C, Conner N, Aroian K. Flourishing: An evolutionary concept analysis. Issues in Mental Health Nursing 2017; 38(11): 915-23.

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Recognizing Other Risk Factors for Toxic Stress

A circumstance, exposure, or condition with documented associations with increased likelihood or susceptibility of development of the toxic stress response.

In addition to ACEs, other risk factors for toxic stress include poverty, exposure to discrimination, and exposure to the atrocities of war.

Source: Nelson CA, Bhutta ZA, Burke Harris N, Danese A, Samara M. Adversity in childhood is linked to mental and physical health throughout life. BMJ (Clinical Research Edition) 2020; 371: m3048.

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The Biology of Adversity

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Childhood Adversity, Biological Changes, and Adult Outcomes

Source: Nelson CA, Bhutta ZA, Burke Harris N, Danese A, Samara M. Adversity in childhood is linked to mental�and physical health throughout life. BMJ (Clinical Research Edition) 2020; 371: m3048.

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Sources: Listed in References (end)

Source: Adapted from Bucci, M., Marques, S. S., Oh, D., & Harris, N. B. (2016). Toxic stress in children and adolescents. Advances in Pediatrics, 63(1), 403-428.

Adverse Childhood Experiences can generate chronic activation of the stress response system

Toxic stress is a physiological response

This stress response system is a fantastic evolutionary response against snakes in the middle of the trail and may keep us alive in overwhelmingly stressful situations such as neglect, violence, and loss. But what if there are scary snakes at home every night? What if a child perceives a snake around every corner, and their stress response becomes chronically activated?

Constant or repeated re-activation can lead to a hyperactive or dysregulated system. At some point, our brains and bodies adapt and become really good at detecting and reacting to threats, even when the snake is no longer around.

It goes from being adaptive and life saving to maladaptive and health damaging.

ACEs – stressors – risk factors for toxic stress but not destiny – depends on protective factors and predisposing vulnerabilities

Toxic stress is the physiologic response – this NEI dysregulation

That then leads to poor health outcomes

The clinical implications of a dysregulated threat response system included dysregulation of our neuro, endocrine and immune systems.

Looking at our Endocrine system

• Long-term changes in ACTH, cortisol, adrenaline and other hormones leads to increased stress activation in the body.

• Changes in Growth Hormone, thyroid hormone and pubertal hormones lead to changes in growth, development, metabolism and puberty

• Changes to leptin and ghrelin lead to increased risk of overweight and obesity.

Stress hormones promote insulin resistance making it more difficult to manage our blood sugar

Neurologically -

• Over Activation of the amygdala can lead to increased fear response

• Inhibition of the prefrontal cortex — impaired executive functioning

• Hippocampal neurotoxicity — difficulty with learning and memory

These children often get misdiagnosed as having ADHD.

Looking at our Immune system

• There is dysregulation that can lead to increases in sympathetic nervous system racheting up the immune system leading to increased risk for auto-immune disease and/or

increases in HPA-axis/cortisol system leading to inhibition of inflammatory pathways and increased risk for repeated infections.

Increased inflammation and increased BP - leads to increased wear and tear on the endothelium lining

All of these changes are embedded in a long term way in our biology through epigenetic mechanisms.

In addition, adversity in childhood leads to telomere erosion which leads to premature cell death and altered cell replication, which increases risk for disease (such as diabetes) and cancer.

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Source: Bucci, M., S. S. Marques, D. Oh, and N. B. Harris. 2016. Toxic stress in children and adolescents. Advances in Pediatrics 63(1):403–428.

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Assess for ACE- Associated Health Conditions

ADHD

Aggression/fighting

Alcohol/Drug Use

Anxiety

Depression

Developmental Delay

Enuresis

Encopresis

Headaches

Learning Problems

Pain

PTSD

Cardiovascular Disease

Diabetes

Failure to Thrive

Hepatitis

Late menarche

Overweight

Obesity

Stroke

Allergies

Arthritis

Asthma

COPD

Eczema

Increased infections

Urticaria

Source: Rachel Gilgoff Presentation. Bhushan D, Kotz K, McCall J, Wirtz S, Gilgoff R, Dube SR, Powers C, Olson-Morgan J, Galeste M, Patterson K, Harris L, Mills A, Bethell C, Burke Harris N, Office of the California Surgeon General. Roadmap for Resilience: The California Surgeon General’s Report on Adverse Childhood Experiences, Toxic Stress, and Health. Office of the California Surgeon General, 2020. DOI: 10.48019/PEAM8812. (p. 12-32)

ACE Associated Health Conditions can be organized into the categories of Neuro, Endo/Metabolic and Immune as a way to help assess for signs of NEI dysregulation.

While ACEs are known to be associated with elevated risk for poor physical health even in childhood (e.g. failure to thrive, asthma, obesity), in practice it may be difficult to see beyond the behavioral

and mental health issues and symptoms (e.g. ADHD, oppositional behavior, school problems, drug use, depression, anxiety, violence). The hope is that grouping health conditions by NEI can support providers in linking what may seem to be disparate medical conditions (both mental and physical health issues) with the underlying toxic stress a child may be experiencing. ACE screening plus the AAHCs may point to a change in diagnosis.

For example, while there are potentially many causes for ADHD, Autism or Oppositional Defiance Disorder including a spectrum of normal neurodiversity, ACE screening and further assessment, including the assessing for health conditions may identify which symptoms are manifestations of a trauma reaction, leading to a diagnosis of Developmental Trauma Disorder. This checklist can aid providers in assessing which symptoms may be

indicative of a toxic stress response in the presence of exposure to ACEs, consider differential diagnostic approaches as well as treatment and follow-up plans, and better determine whether a dysregulated

neuroendocrine-immune system is at the root of the medical problem.

Source: Bhushan D, Kotz K, McCall J, Wirtz S, Gilgoff R, Dube SR, Powers C, Olson-Morgan J, Galeste M, Patterson K, Harris L, Mills A, Bethell C, Burke Harris N, Office of the California Surgeon General. Roadmap for Resilience: The California Surgeon General’s Report on Adverse Childhood Experiences, Toxic Stress, and Health. Office of the California Surgeon General, 2020. DOI: 10.48019/PEAM8812. (p. 12-32)

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Biological Systems Disrupted by Toxic Stress

System	Mechanism(s)	Health Impact
Neurologic; Neuroendocrine	Dysregulation of SAM and HPA axes; autonomic imbalance	Difficulty modulating, sustaining, or dampening the stress response; heightened or blunted stress sensitivity
	Altered reactivity and size of the amygdala	Increased fear responsiveness, impulsivity, and aggression
	Inhibition of the prefrontal cortex	Impaired executive function, with poorer planning, decision-making, impulse control, and emotion regulation
	Hippocampal neurotoxicity	Difficulty with learning and memory
	VTA and reward processing dysregulation	Increased risky behaviors and risk of addiction
Immunologic; Inflammatory	Increased inflammatory markers, especially Th2 response; inhibition of anti-inflammatory pathways; gut microbiome dysbiosis	Increased risk of infection, auto-immune disorders, cancers, chronic inflammation; cardiometabolic disorders
Endocrine; Metabolic	Changes in growth hormone, thyroid hormone, and pubertal hormonal axes	Changes in growth, development, basal metabolism, and pubertal events
Endocrine; Metabolic	Changes to leptin, ghrelin, lipid and glucose metabolism, and other metabolic pathways	Increased risk of overweight, obesity, cardiometabolic disorders, and insulin resistance
Epigenetic; Genetic	Sustained changes to the way DNA is read and transcribed	Mediates all aspects of the toxic stress response
Epigenetic; Genetic	Telomere erosion, altered cell replication, and premature cell death	Increased risk for disease, cancer, and early mortality

Source: Bhushan D, Kotz K, McCall J, Wirtz S, Gilgoff R, Dube SR, Powers C, Olson-Morgan J, Galeste M, Patterson K, Harris L, Mills A, Bethell C, Burke Harris N, Office of the California Surgeon General. Roadmap for Resilience: The California Surgeon General’s Report on Adverse Childhood Experiences, Toxic Stress, and Health. Office of the California Surgeon General, 2020. DOI: 10.48019/PEAM8812. (p. 21, Table 4)

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Source: Bhushan D, Kotz K, McCall J, Wirtz S, Gilgoff R, Dube SR, Powers C, Olson-Morgan J, Galeste M, Patterson K, Harris L, Mills A, Bethell C, Burke Harris N, Office of the California Surgeon General. Roadmap for Resilience: The California Surgeon General’s Report on Adverse Childhood Experiences, Toxic Stress, and Health. Office of the California Surgeon General, 2020.

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The Clinical Response to ACEs and Toxic Stress

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Toxic Stress is Amenable to Treatment

New opportunities to more precisely interrupt the toxic stress response, break the intergenerational cycle of ACEs and toxic stress, and promote an intergenerational cycle of health.
Early intervention can improve brain, immune, hormonal, and genetic regulatory control of development.
Treatment of toxic stress in adults may prevent transmission of neuro-endocrine-immune-metabolic and genetic regulatory disruptions in offspring.

Sources: Gilgoff et al. Adverse Childhood Experiences, outcomes, and interventions. Pediatric Clinics 2020; 67(2): 259-73; Purewal Boparai et al. Ameliorating the biological impacts of childhood adversity: A review of intervention programs. Child Abuse & Neglect 2018; 81: 82-105; National Academies of Sciences, Engineering, and Medicine. Vibrant and healthy kids: Aligning science, practice, and policy to advance health equity. Washington, DC: National Academies Press, 2019. Blaisdell et al. Early adversity, child neglect, and stress neurobiology: From observations of impact to empirical evaluations of mechanisms. International Journal of Developmental Neuroscience 2019; 78: 139-46. ; Jaffee et al. Safe, stable, nurturing relationships break the intergenerational cycle of abuse: A prospective nationally representative cohort of children in the United Kingdom. Journal of Adolescent Health 2013; 53(4): S4-S10.

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Clinical Response to ACEs and Toxic Stress

Applying principles of trauma-informed care including establishing trust, safety, and collaborative decision-making.
Supplementing usual care for ACE-Associated Health Conditions by providing patient education on toxic stress and offering strategies to regulate the stress response (using seven evidence-based strategies for toxic stress regulation – “stress busters”).
Validating existing strengths and protective factors.
Referrals to patient resources or interventions, such as educational materials, social work, school agencies, care coordination or patient navigation, community health workers.
Follow-up as necessary, using the presenting ACE-Associated Health Condition(s) as indicators of treatment progress.

So what can we do across the lifespan? ACEs are preventable and Toxic Stress is a health condition that is treatable.

To go through this slide briefly just to point out that a full effective clinical response should include

1. Trauma-informed care.

2. Calm the threat response system

Put out the fire
Safety
Care coordination, social work

Strategies for thinking about ACE Associated health conditions as symptoms of toxic stress

3. Using a strengths based approach and evaluating for protective factors

4. Thinking about what I can do in my clinical practice and when I need to refer for for additional services

5 And thinking about more frequent follow-up for patients who have higher toxic stress- related needs.

Bhushan D, Kotz K, McCall J, Wirtz S, Gilgoff R, Dube SR, Powers C, Olson-Morgan J, Galeste M, Patterson K, Harris L, Mills A, Bethell C, Burke Harris N, Office of the California Surgeon General. Roadmap for Resilience: The California Surgeon General’s

Report on Adverse Childhood Experiences, Toxic Stress, and Health. Office of the

California Surgeon General, 2020. DOI: 10.48019/PEAM8812. p 79-80.

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Strategies for Regulating the Toxic Stress Response

Source: Adapted from Burke Harris, Nadine. The Deepest Well: Healing the Long-Term Effects of Childhood Adversity. Boston: Houghton Mifflin Harcourt, 2018;

Gilgoff et al. Adverse Childhood Experiences, outcomes, and interventions. Pediatric Clinics 2020; 67(2): 259-73;

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When we are screening for ACEs, ACE Associated Health Conditions and protective factors - what is that we – in that clinic moment - really want to know – we want to know what can we do in that clinical visit to help.

And these 7 areas, these evidence based strategies have all been shown to “reduce stress hormones, reduce inflammation, and enhance neuroplasticity—key mechanisms to counteract the toxic stress response and improve overall health and well-being.”

these are the things that we as providers can use to treat toxic stress in the clinic.

I have heard people say that we shouldn’t screen for ACEs because we don’t have treatments or interventions or enough mental services. And if you get one thing from this slide, I hope it is this - that toxic stress is treatable and we have tools and strategies to help people heal their physiology.

And we do this by focusing on creating safety for that patient by helping to actually stop any current active threats and by using these 7 strategies with a trauma-informed lens.

Starting with supportive relationships - We can assess whether the patient and their caregivers have a safe, supportive and nurturing person in their life – We ask about how much our patients smoke, drink and exercise but how often do we ask who will bring them chicken soup when they are sick? Who can they talk to when they feel sad or scared?

– and do they feel connected to their community – do they feel they belong in a group. And if not – we can help connect them to support groups, team sports, parenting classes, home visiting, mental health interventions.

Sleep. When we talk to parents about helping their child sleep we talk about bedtime routines, reading books, no TV right before bed. All important things for good sleep hygeine. But what if the child can’t sleep because mom and dad are screaming in the other room? What if the child can’t sleep because they are worried about the bully at school? These involve additional discussions and potential interventions. Helping the caregiver be a buffer. Helping the child have stress-management tools like a journal before bed or worry dolls.

Nutrition - the SNS is the immediate stress hormone - it stops digestion, makes us not hungry. The HPA axis is the longer term stress hormone and actually tells us to stock up for future threats. Depeding on the preson, the adversity, the time course, both of these hormones could account for a person losing wieght or gaining weight when stressed. So blaming people for this biology won’t help them counter it.

And unfortunately fast food and processed foods are inflammatory making things worse.

But we can talk to patients about this biology, take away blame and shame, and explain that fresh fruits and vegetables, and unprocessed foods are anti-inflammatory and can counter the inflammation from stress.

Exercise - if a child has high ACEs, has increased stress hormones telling the body to release energy - glucose, amino acids into the blood - but then they have to sit still in class or can’t go outside - where does all of the extra energy go? This is one way that exercise can specifically help calm kids, adults down. It can help us metabolize that extra energy – decrease risk for diabetes, inflammation, improve cognitive functioning

Mindfulness - mindfulness is a way to practice listening to our body, be aware of our emotions, and create a space between sensory input and reaction. If sensory input comes into our amygdala before our frontal lobe can say “wait wait it’s just a stick” then we are going to react. But if we practice breathing, pausing we are actually practicing that moment when a stressful event happens and teaching our amygdala to pause and let the pfc catch up.

Nature Letting everyone know that Nature can come in many forms, including parks, local green spaces, playgrounds, and even indoor plants. And that Access and exposure to these natural environments can improve health. You can write a prescription for nature. Parksrx.org has resources for how to make that happen. Referral to ecotherapy and adventure-based mental health programs.

Mental health - This could include referrals to mental health providers as well as medications. I think it is also important to know that just like medical professionals, mental health professionals also have areas of expertise. And so for patients who have active significant safety or mental/behavioral health needs - It is important to help individuals connect with therapists who can provide trauma-focused services.

Bhushan D, Kotz K, McCall J, Wirtz S, Gilgoff R, Dube SR, Powers C, Olson-Morgan J, Galeste M, Patterson K, Harris L, Mills A, Bethell C, Burke Harris N, Office of the California Surgeon General. Roadmap for Resilience: The California Surgeon General’s Report on Adverse Childhood Experiences, Toxic Stress, and Health. Office of the California Surgeon General, 2020. DOI: 10.48019/PEAM8812.

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Buffering the Toxic Stress Response - examples

Neurologic/Neuroendocrine: MRI studies found that institutionalized children randomized to high-quality nurturant caregiving showed normalization of the developmental trajectory of white matter structures. Responsive caregiving also improves cortisol reactivity in children. Time in nature reduces sympathetic nervous system activity and increases parasympathetic activity.
Immunologic: Meditation was associated with decreased IFN-γ and NK cell production of IL-10 and with increased T cell production of IL-4 (anti-inflammatory). Healthy sleep reduces infection risk and improves vaccination response, increasing NK cell activity, IL-6, and TNF-alpha levels. Moderate exercise decreases infection risk.
Endocrine/Metabolic: Oxytocin inhibits the stress response, enhances bonding, protects against stress-induced cell death, has anti-inflammatory effects, enhances metabolic homeostasis, and protects vascular endothelium. Social support buffers stress-related cardiovascular reactivity and decreases catecholamine levels. The Mediterranean diet reduces inflammation and risk for depression, cardiovascular disease, diabetes, and mortality.
Epigenetic: Meany and colleagues found that nurturant caregiving was associated with epigenetic changes that led to greater stress tolerance, more normal functioning of the stress response, and improved cognitive performance.

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Using Motivational Interviewing with the�Evidence-Based Strategies for Mitigating Toxic Stress

Supportive relationships, including with caregivers (for children), other family members, and peers

High-quality, sufficient sleep

Balanced nutrition

Regular physical activity

Mindfulness and meditation

Experiencing nature

Mental health care, including psychotherapy or psychiatric �care, and substance use disorder treatment, when indicated

(After introducing the strategies at right)

Check in about how the family is doing with each of the strategies (see box at right):

“On a scale of 1 to 10, tell me where you’re at with each of these strategies?”

Listen for family strengths and validate what they are doing well:

“Wow, your child is on the basketball team! Your family does a great job with exercise.”
“It sounds like you really pay attention to your family’s nutrition. That’s great!”

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Using Motivational Interviewing with the�Evidence-Based Strategies for Mitigating Toxic Stress (cont.)