The Science of ACEs & Toxic Stress

ACEs and toxic stress can affect health, but toxic stress is treatable

Clinical teams have an important role to play in screening for ACEs and preventing and treating toxic stress to improve patients’ physical and mental health.

Understanding the science of ACEs and toxic stress and how it can manifest in the body is critical to effective treatment planning for patients.

ACEs are strongly associated, in a dose-response fashion, with some of the most common, serious, and costly health conditions facing our society today, including nine of the 10 leading causes of death in the U.S., as well as earlier mortality. (1) (2)

Toxic Stress

A consensus of scientific evidence demonstrates that high doses of cumulative adversity experienced during critical and sensitive periods of periods of early life development – without the buffering protections of trusted, nurturing caregivers and safe, stable environments – can lead to long-term disruptions in brain development and immune, hormonal, and metabolic systems, acting through genetic regulatory mechanisms. This condition is now known as the toxic stress response. (3) (4) (5) (6)

Not all stress is bad. Some stress is a necessary and even essential part of growth and development; it can help us transiently mobilize energy and increase focus to perform better at the task at hand, such as an upcoming test, the big game, or a presentation at work. There are 3 types of stress:

  • Positive Stress: Brief elevations in stress hormones, heart rate, and blood pressure in response to a routine stressor (e.g., a test, game).
  • Tolerable Stress: Time-limited activation of the stress response that if buffered by relationships with adults who help the child adapt, the brain and other organs recover (e.g., natural disaster).
  • Toxic Stress: High doses of adversity experienced during critical and sensitive periods of early development, without adequate buffering protections, can become “biologically imbedded” leading to the toxic stress response (e.g., ACEs).

Other Risk Factors for Toxic Stress

In addition to ACEs, exposure to other adversities, such as poverty, racism and discrimination, and housing and food insecurity, are associated with health risks and are also believed to be risk factors for toxic stress. However, whether and to what extent these factors act through the toxic stress response is still under investigation.

The Impact of ACEs and Toxic Stress on Health

ACEs and toxic stress are associated with increased risk of a wide range of health conditions in both pediatric and adult populations, known as ACE-Associated Health Conditions. The life expectancy of individuals with six or more ACEs is 19 years shorter than that of individuals with none. (7)

Below is a list of key ACE-Associated Health Conditions for populations by age. Click here for a more complete list of ACE-Associated Health Conditions for children and adults.

  • Failure to thrive
  • Growth delay
  • Sleep disruption
  • Developmental delay
  • Increased risk of viral infections
  • Pneumonia
  • Asthma and other atopic diseases
  • Other atopic diseases
  • Difficulties with learning and behavior
  • Somatic complaints, including headache and abdominal pain
  • Increased engagement in high-risk behaviors
  • Teen pregnancy
  • Teen paternity
  • Sexually transmitted infections (STIs)
  • Mental health disorders
  • Substance use
  • Diabetes
  • Chronic obstructive pulmonary disease (COPD)
  • Cardiovascular disease
  • Stroke
  • Cancer
  • Depression
  • Anxiety
  • Substance use
  • Chronic pain
  • Post-traumatic stress disorder


1: Centers for Disease Control and Prevention. Leading causes of death by age group 2017. (accessed May 8, 2019).
2: 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.
3: Shonkoff JP, Garner AS, Dobbins MI, et al. The lifelong effects of early childhood adversity and toxic stress. Pediatrics 2012; 129: e232–46.
4: 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.
5: 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.
6: Bucci M, Marques SS, Oh D, Harris NB. Toxic Stress in Children and Adolescents. Advances in Pediatrics 2016; 63: 403–28.
7: 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.