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.

But there is hope. We can take action now to change and save lives. The impacts of ACEs and toxic stress are treatable.

female doctor talking on phone

Adverse Childhood Experiences

The term Adverse Childhood Experiences (ACEs) comes from the landmark 1998 study by the Centers for Disease Control and Prevention (CDC) and Kaiser Permanente. (1) (2) It describes 10 categories of adversities in three domains experienced by age 18 years:

  • Abuse: physical, emotional, or sexual
  • Neglect: physical or emotional
  • Household dysfunction: growing up with household incarceration, mental illness, substance dependence, parental separation or divorce, or intimate partner violence

Data show that 62% of California residents have experienced at least one ACE and 16% have experienced four or more ACEs, using 2011-2017 Behavioral Risk Factor Surveillance System (BRFSS) data from a random-digit-dialed telephone survey. (3)

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

  1. ACEs are highly prevalent. Two thirds of respondents in the ACE Study reported at least one ACE and one in eight reported four or more ACEs. Subsequent studies have shown a rate of four or more ACEs that is closer to one in six. (4) (5)
  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 at least nine of the 10 leading causes of death in the U.S. (6) (7)
  3. ACEs affect all communities. The original ACE Study was conducted among a population that was mostly Caucasian, middle class, employed, college educated, and privately insured. Subsequent studies have found higher prevalence rates of ACEs in people who are low-income, of color, justice-involved, and/or part of the lesbian, gay, bisexual, transgender, and queer (LGBTQ+) community. (8) (9) (10) (11) (12)

Toxic Stress

Several decades of scientific research have 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, without the buffering protections of trusted, nurturing caregivers and safe, stable environments, 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. (13) (14) (15) (16)

These biological changes play an important role in the clinical progression from ACE exposure to negative short- and long-term health and social outcomes. Further, both the disrupted biology and the associated negative outcomes demonstrate a pattern of high rates of intergenerational transmission. Development of the toxic stress response is influenced by a combination of cumulative adversity, buffering or protective factors, and predisposing vulnerability.

In addition to ACEs, social determinants of health (SDOH), such as poverty, discrimination, and housing and food insecurity, are associated with health risks and may also be risk factors for toxic stress. 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. The life expectancy of individuals with six or more ACEs is 19 years shorter than that of individuals with none. (17)

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 (STIs), mental health disorders, and substance use – are common.
  • Adult Health: ACEs are associated with some of the most common and serious health conditions facing our communities. (18) People with 4 or more ACEs are:
    • 37.5 x as likely to attempt suicide (19)  
    • 3.2 x as likely to have chronic lower respiratory disease (20)
    • 2 to 2.3 x as likely to have a stroke, (21)  cancer, (22) or heart disease (23)
    • 1.4 as likely to have diabetes (24)

The higher the ACE score, the greater the risk for ACE-Associated Health Conditions.

  • Mental and Behavioral Health: The higher the ACE score, the greater the likelihood an individual may experience mental health disorders such as depression, post-traumatic stress disorder, anxiety, and sleep disorders, and to engage in risky behaviors such as early and high-risk sexual behaviors and substance use. (25) (26) High doses of childhood adversity are associated with increased risk of engaging in high-risk behaviors that can lead to negative health outcomes.

However, even in the absence of health-damaging behavior, strong associations between cumulative childhood adversity and increased risk of serious health conditions persist. Evidence suggests that the toxic stress response likely plays a role in mediating both behavior-related and non-behavior-related pathways.


1, 21: 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.
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3: 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.
4: 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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6, 18: Centers for Disease Control and Prevention. Leading causes of death by age group 2017. (accessed May 8, 2019).
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26: 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.