The Science of ACEs & Toxic Stress

A consensus of scientific research demonstrates that cumulative adversity, especially when experienced during childhood development, is a root cause to some of the most harmful, persistent, and expensive health challenges facing our nation.

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Adverse Childhood Experiences

The term Adverse Childhood Experiences (ACEs) comes 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. (1) (2) The term ACEs specifically refers to the 10 categories of adversities in 3 domains that were evaluated in the study:

  • Abuse: physical, emotional, or sexual
  • Neglect: physical or emotional
  • Household dysfunction: growing up in a household with parental incarceration, mental illness, substance use, absence due to separation or divorce, or intimate partner violence (initially queried as violence towards the mother or stepmother).

A child or adolescent who experiences ACEs without the buffering effects of trusted, nurturing caregivers and safe, stable environments can develop a toxic stress response, which can impact brain development, hormone and immune systems, and genetic regulatory systems. (3)

Key findings of the ACE Study and subsequent body of research include:

  1. ACEs are highly prevalent. Two thirds of respondents in the Kaiser/CDC study reported at least 1 ACE and one in eight reported 4 or more ACEs.
  2. ACEs are strongly associated, in a dose-response fashion, with some of the most common and serious health conditions facing our society today, including 9 of the 10 leading causes of death in the United States. (4) (5)
  3. ACEs affect all communities. The original ACE Study was conducted among a population that was 70% Caucasian, mostly middle class, college-educated, and privately insured. Subsequent studies have found higher prevalence rates of ACEs in communities that are low-income, LGBTQ, and of color. (6) (7) (8) (9) (10)

Toxic Stress

The past several decades of scientific research has identified the biological mechanisms by which early adversity leads to increased risk of negative health and social outcomes through the life course. Repeated or prolonged activation of a child’s stress response, in absence of adequate buffering caregiving support, leads to long-term changes in the structure and functioning of the developing brain, metabolic, immune, and neuroendocrine responses, and even the way DNA is read and transcribed. This is known as the toxic stress response. (11) (12) (13) (14)

These biological changes play an important role in the clinical progression from ACE exposure to negative short- and long-term health and social outcomes and demonstrate a pattern of high rates of intergenerational transmission.

Social determinants of health (SDOH) other than ACEs, such as poverty, discrimination and housing insecurity are associated with health risks and may also be risk factors for toxic stress. However, these factors should NOT be confounded with ACEs in characterizing risk of negative health and social outcomes.

While validated odds ratios are available in large, population-based studies utilizing the 10 standardized ACE criteria, the strengths of associations between SDOH and health outcomes have not been similarly standardized.

The Impact of ACEs and Toxic Stress on Health

ACEs are associated with increased risk of a wide range of health conditions in both pediatric and adult populations. These ACE-Associated Health Conditions include:

  • Pediatric Health: The effects of toxic stress are detectable as early as infancy. In babies, high doses of adversity are associated with failure to thrive, growth delay, sleep disruption and developmental delay. School-aged children may have increased risk of viral infections, pneumonia, asthma and other atopic diseases, as well as difficulties with learning and behavior. Among adolescents with high ACEs, somatic complaints including headache and abdominal pain, increased engagement in high-risk behaviors, teen pregnancy, teen paternity, sexually transmitted infections, mental health disorders, and substance use are common.
  • Adult Health: Research shows that individuals who have experienced ACEs are at significantly increased risk of serious health consequences, including 9 of the 10 leading causes of death. (15) People with 4 or more ACEs are:
    • 3 x as likely to have chronic lower respiratory disease (16)
    • 2 to 2 ½ x as likely to have a stroke, (17)  cancer, (18) or heart disease (19)
    • 1 ½ x as likely to have diabetes (20)
    • 38 x as likely to attempt suicide (21)  
    • 11 x as likely to have Alzheimer’s or dementia (22)
  • Mental and Behavioral Health: The higher the ACE score, the more likely the individual is to experience mental health conditions including depression, post-traumatic stress disorder, anxiety, and eating disorders, and to engage in risky behaviors such as early and high-risk sexual behaviors and substance use. (23) (24)
  • Life Expectancy: Individuals with 6 or more ACEs have a life expectancy that is 19 years shorter than individuals with none. (25)


1, 17: Felitti VJ, Anda RF, Nordenberg D, et al. Relationship of Childhood Abuse and Household Dysfunction to Many of the Leading Causes of Death in Adults. American Journal of Preventive Medicine 1998; 14: 245–58.
2: Dube SR, Felitti VJ, Dong M, Giles WH, Anda RF. The impact of adverse childhood experiences on health problems: evidence from four birth cohorts dating back to 1900. Preventive Medicine 2003; 37: 268–77.
3: Purewal Boparai SK, Au V, Koita K, et al.. Ameliorating the biological impacts of childhood adversity: A review of intervention programs. Child Abuse & Neglect 2018; 81: 82-105.
5, 6: Merrick MT, Ford DC, Ports KA, Guinn AS. Prevalence of adverse childhood experiences from the 2011-2014 Behavioral Risk Factor Surveillance System in 23 states. JAMA Pediatrics 2018; 172: 1038.
7: Vásquez E, Udo T, Corsino L, Shaw BA. Racial and Ethnic Disparities in the Association Between Adverse Childhood Experience, Perceived Discrimination and Body Mass Index in a National Sample of U.S. Older Adults. J Nutr Gerontol Geriatr 2019; 38: 6–17.
8: Maguire-Jack K, Lanier P, Lombardi B. Investigating racial differences in clusters of adverse childhood experiences. American Journal of Orthopsychiatry 2019; published online Feb 28. DOI:10.1037/ort0000405.
9: Liu SR, Kia-Keating M, Nylund-Gibson K. Patterns of adversity and pathways to health among White, Black, and Latinx youth. Child Abuse & Neglect 2018; 86: 89–99.
10: Liu SR, Kia‐Keating M, Nylund‐Gibson K, Barnett ML. Co‐Occurring Youth Profiles of Adverse Childhood Experiences and Protective Factors: Associations with Health, Resilience, and Racial Disparities. American Journal of Community Psychology 2019; published online Sept 6. DOI:10.1002/ajcp.12387.
11: Shonkoff JP, Garner AS, Dobbins MI, et al. The lifelong effects of early childhood adversity and toxic stress. Pediatrics 2012; 129: e232–46.
12: 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.
13: 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.
14: Bucci M, Marques SS, Oh D, Harris NB. Toxic Stress in Children and Adolescents. Advances in Pediatrics 2016; 63: 403–28.
16, 18, 19, 20, 21, 23: 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.
22: Center for Youth Wellness. Data Report: A Hidden Crisis. Findings on Adverse Childhood Experiences in California. 2014.
24: Shin, S. H., E. Edwards, T. Heeren, and M. Amodeo. 2009. Relationship between multiple forms of maltreatment by a parent or guardian and adolescent alcohol use. The American Journal on Addictions 18(3):226–234.
25: Brown DW, Anda RF, Tiemeier H, et al. Adverse childhood experiences and the risk of premature mortality. American Journal of Preventive Medicine 2009; 37: 389–96.