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Adverse Childhood Experiences (ACEs) and Adult Inflammation: Anti-Inflammatory & other Effects of Exercise

Original Editor - Andrea Sturm

Top Contributors - Tarina van der Stockt, Jess Bell, Simisola Ajeyalemi, Lucinda hampton and Kim Jackson  

Adverse Childhood Experience (ACE)

Adverse childhood experience (ACE) refers to a traumatic event, or events, occurring early in life (i.e., before 18 years of age).[1] This includes abuse, neglect, exposure to domestic violence, accidents, community violence, and traumatic medical or surgical procedures.[2] Childhood trauma is relatively common — more than 60 percent of children are exposed to trauma by 16 years old and more than 30 percent experience multiple events.[3] Around 80 percent of maltreatment is by a child's own parents. ACEs represent a significant public health challenge, though with appropriate intervention and prevention, their impact can be reduced.

Complex trauma is "the experience of multiple, chronic and prolonged, developmentally adverse traumatic events, most often of an interpersonal nature (e.g., sexual or physical abuse, war, community violence) and early-life onset."[2]

Any traumatic childhood experience has a significant impact on a child's life growing up and extends into adulthood. It is well documented that ACEs can affect an individual's physical and mental health in later life.[4][5][6][7] For example, children who experience domestic violence or parental alcoholism may develop a range of symptoms, including depression, medical conditions, and self-destructive or impulsive behaviours. However, these are often addressed one by one rather than considered as a connected whole. A reason for this is that, due to social taboos, medical and psychiatric examinations do not always include questions about childhood trauma (e.g., violence, abuse and neglect), meaning that the root cause may go unrecognised.[2][8]

Kaiser Permanente and the Centers for Disease Control and Prevention conducted a landmark ACE study in which 17,337 adults completed a questionnaire about childhood experiences of abuse, neglect, and family dysfunction.

The findings revealed high rates of ACEs: 30.1% of participants reported physical abuse, 19.9% sexual abuse, and 11% emotional abuse. Participants also reported childhood exposure to family alcohol abuse (23.5%), mental illness (18.8%), domestic violence (12.5%), and family drug abuse (4.9%). The study demonstrated that ACEs are common and can affect adult health decades later.[2]

The authors found a "highly significant relationship between adverse childhood experiences and depression, suicide attempts, alcoholism, drug abuse, sexual promiscuity, domestic violence, cigarette smoking, obesity, physical inactivity, and sexually transmitted diseases. In addition, the more adverse childhood experiences reported, the more likely a person was to develop heart disease, cancer, stroke, diabetes, skeletal fractures, and liver disease."[2]

Childhood Trauma and Adulthood Inflammation

A meta-analysis by Baumeister et al. (2016) investigated whether adversity in early life contributes to a pro-inflammatory state in adulthood.[9] The authors found a significant association between childhood trauma and inflammatory markers, with the greatest effect sizes being for tumour necrosis factor-α (TNF-α), followed by interleukin-6 (IL-6), and C-reactive protein (CRP). This demonstrates that traumatic childhood experiences have a lasting impact on the inflammatory immune system that follows the child into adulthood. The authors describe this as a "molecular pathway by which early trauma confers vulnerability to developing psychiatric and physical disorders later in life".[9]

Further studies are needed to explore the molecular mechanisms involved. The increase in immune activation might be explained by changes in epigenetic regulation of gene expression. There is also evidence that childhood trauma induces the following:[9]

  • modifications of hypothalamic-pituitary-adrenal (HPA) and neuroplasticity-related methylation patterns
  • greater demethylation of FKBP5, a heat-shock protein that binds and then inhibits the glucocorticoid receptor (GR)
  • greater methylation of the GR, a crucial regulator of inflammatory activity, leading to reduced GR function and exacerbated inflammation
  • a cycle in which inflammation further impairs GR function, leading to GR resistance into adulthood[9]

Specific inflammatory profiles are also linked to specific types of trauma:[9]

  • physical and sexual abuse leads to increased TNF-α and IL-6 (CRP is not increased)
  • absence of a parent during early developmental years is related to CRP

Mental health conditions can be linked to different types of trauma:[9]

  • physical or sexual childhood abuse can lead to specific subtypes of anxiety disorders
  • childhood sexual abuse can lead to the development of auditory verbal hallucinations in psychosis

The Anti-Inflammatory Actions of Exercise Training

An increasing number of diseases are recognised as having an inflammatory origin. The following conditions have been linked to or shown to be exacerbated by poorly regulated inflammatory processes: cardiovascular disease, diabetes, osteoporosis, Alzheimer's disease and geriatric cachexia (a syndrome with symptoms of weight loss, reduction in muscle mass, and decreased physical activity).[10][11] These chronic diseases mostly occur in older or more sedentary people.[10]

Physical activity decreases inflammation through several mechanisms, including changes in cytokine release, down-regulation of toll-like receptors, reduction of visceral adipose tissue, and increased vagal tone.[12]

A growing body of research shows biomarkers linked with chronic inflammation are reduced in people who are, or become physically active. Previously, this decrease was attributed to weight loss or changes in body mass index (BMI), but more recently, studies suggest that exercise has "body fat–independent anti-inflammatory effects"[10] — an effect that appears to occur regardless of age or the presence of chronic disease. Adults who are physically active have a significant decrease in low-grade systemic inflammatory markers.[10] 

Chronic low-grade inflammation is described as a more subtle form of inflammation than that seen in the acute phase. It is often measured using circulating C-reactive protein (CRP). CRP levels are higher in individuals with a high BMI, those who smoke, and those with metabolic syndrome, diabetes, low high-density lipoprotein cholesterol or chronic infection. Low-grade inflammation causes more diffuse damage across the body and "is apparently associated with several organs and tissues such as endothelial cells and adipocytes".[10] CRP has also been linked atherogenesis and there is some evidence that it contributes to damage following myocardial infarction.[10]

Tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) stimulate CRP release from the liver and are both linked to an "increased incidence of disease, physical frailty or muscle wasting, and early death".[10] TNF-α and IL-6 are frequently measured alongside IL-10 (anti-inflammatory cytokine) and the adipocytokine adiponectin. Adiponectin is inversely released to fat mass and it has an anti-inflammatory action, negating the influence of TNF-α.[10]  

Research suggests that exercise may induce the release of "heat shock proteins, shifts in immune cell phenotype, training-induced reductions in visceral adipose tissue, or reduced tissue hypoxia".[10] Exercise is considered a cost-effective, easily available and effective management strategy for low-grade systemic inflammation it positively influences chronic disease.[10]

Exercise also changes the composition of the gut microbiome, which in turn affects inflammation. Exercise has been described as a "natural strong anti-inflammatory strategy to improve brain function".[13] The vagus nerve connects the brain to the abdomen and regulates metabolic homeostasis. Physical activity increases vagal tone, which modifies the inflammatory reflex and decreases systemic inflammation. [12] Individuals with higher levels of inflammation tend to experience more stress, depression and anxiety. Thus, exercise can decrease inflammation and improve mental health by improving the "gut-brain axis".[12]

It should be noted, however, that very high intensity exercise can have a negative effect, as it may increase the risk for upper respiratory tract infections by decreasing the effectiveness of the immune system.[12]

Exercise for Mental Health

Lifestyle modification, especially exercise, is a cost-effective strategy for improving health and quality of life, and is particularly important for people with serious mental illness.[14] However, exercise is often overlooked in the treatment of these individuals and poorly understood by both patients and health-care practitioners.[14] People with serious mental disease have a greater risk of developing chronic conditions, such as diabetes, hyperlipidemia, and cardiovascular disease, due to a sedentary lifestyle and side effects from medication.[14]

Aerobic exercise (such as jogging, swimming, and gardening) can reduce anxiety and depression by increasing blood flow to the brain and influencing the physiological stress response via the hypothalamic-pituitary-adrenal (HPA) axis.[14] The psychological benefits of exercise are also important, including distraction from negative thoughts, improved self-esteem through self-efficacy, and social interaction.[12] [14] Structured group exercises can be effective, but incorporating moderate-intensity exercise or activity on a daily basis is more important.[14] Individuals with mental health disorders adhere to exercise interventions at the same rate as the general population.[14]

"Exercise improves mental health by reducing anxiety, depression, and negative mood and by improving self-esteem and cognitive function. Exercise has also been found to alleviate symptoms such as low self-esteem and social withdrawal".[14]

A three-month study focusing on a conditioning programme for individuals with schizophrenia found improvements in weight control, fitness levels, perceived energy levels, exercise tolerance, upper body strength, and blood pressure.[14]

To achieve these benefits, the recommended guideline is 30 minutes of moderate-intensity activity (such as a brisk walk), three times a week. This does not need to be continuous and can be divided into 10-minute sessions.[14]

Mental health service providers are well placed to deliver effective, evidence-based physical activity interventions for individuals with serious mental illness.[14] Healthcare providers should emphasise and reinforce the following health benefits of regular exercise:[14]

  • improved sleep
  • increased interest in sex
  • better endurance
  • stress relief
  • improvement in mood
  • increased energy and stamina
  • reduced tiredness that can increase mental alertness
  • weight reduction
  • reduced cholesterol
  • improved cardiovascular fitness

Useful Links

The brain changing effects of Exercise by Wendy Suzuki

References

  1. ↑ Egger G, Binns A, Morgan B, Stevens J. Adverse childhood experiences as "upstream" determinants of lifestyle-related chronic disease: a scoping perspective. Am J Lifestyle Med. 2021 Apr 2;16(6):717-22.
  2. ↑ 2.0 2.1 2.2 2.3 2.4 Van der Kolk, B. A. Developmental Trauma Disorder: Toward a rational diagnosis for children with complex trauma histories. Psychiatric Annals. 2005; 35(5), 401-408. 
  3. ↑ Copeland WE, Shanahan L, Hinesley J, Chan RF, Aberg KA, Fairbank JA et al. Association of Childhood Trauma Exposure With Adult Psychiatric Disorders and Functional Outcomes. JAMA Netw Open. 2018;1(7):e184493.
  4. ↑ Shu Y, Zhang Z, Wang H, Wang C, Dou L, Wang W, Zhang L, Bi J, Wu M. The long-term effects of adverse childhood experiences on adult health and behaviors: mediating role of socioeconomic inequality. BMC Public Health. 2025 May 27;25(1):1950.
  5. ↑ He X, Wang M, Du Y, Ye Z, Yang Y, Guo C. The long-term impact of adverse childhood experiences on later-life physical and psychological multimorbidity: A prospective cohort study of middle-aged and older adults in China. J Affect Disord. 2026 May 1;400:121169.
  6. ↑ Trivedi GY, Pillai N, Trivedi RG. Adverse Childhood Experiences & mental health - the urgent need for public health intervention in India. J Prev Med Hyg. 2021 Sep 15;62(3):E728-E735.
  7. ↑ Baldwin JR, Caspi A, Meehan AJ, Ambler A, Arseneault L, Fisher HL, et al. Population vs individual prediction of poor health from results of adverse childhood experiences screening. JAMA Pediatr. 2021 Apr 1;175(4):385-93.
  8. ↑ Sadio AJ, Gbeasor-Komlanvi FA, Mama AH, Tchankoni MK, Koglo KG, Gabkiangbe I, et al. Adverse childhood experiences and mental health in a low-income setting characterised by silence and taboos: a cross-sectional analysis of hidden trauma in Togolese school-going adolescents (2025). BMJ Public Health. 2025 Dec 3;3(2):e003730.
  9. ↑ 9.0 9.1 9.2 9.3 9.4 9.5 Baumeister D, Akhtar R, Ciufolini S, Pariante CM, Mondelli V, Childhood trauma and adulthood inflammation: a meta-analysis of peripheral C-reactive protein, interleukin-6 and tumour necrosis factor-α,  Mol Psychiatry. 2016; 21(5): 642-9. 
  10. ↑ 10.00 10.01 10.02 10.03 10.04 10.05 10.06 10.07 10.08 10.09 Flynn MG, McFarlin BK, Markofski MM. State of the art reviews: The anti-inflammatory actions of exercise training. American Journal of Lifestyle Medicine. 2007 May;1(3):220-35. 
  11. ↑ Gingrich A, Volkert D, Kiesswetter E, Thomanek M, Bach S, Sieber CC, Zopf Y. Prevalence and overlap of sarcopenia, frailty, cachexia and malnutrition in older medical inpatients. BMC geriatrics. 2019 Dec;19(1):120.
  12. ↑ 12.0 12.1 12.2 12.3 12.4 Mikkelsen K, Stojanovska L, Polenakovic M, Bosevski M, Apostolopoulos V. Exercise and mental health. Maturitas. 2017 Dec 1;106:48-56.
  13. ↑ Mee-inta O, Zhao ZW, Kuo YM. Physical exercise inhibits inflammation and microglial activation. Cells. 2019 Jul;8(7):691.
  14. ↑ 14.00 14.01 14.02 14.03 14.04 14.05 14.06 14.07 14.08 14.09 14.10 14.11 Sharma, A., Madaan, V., & Petty, F. D. Exercise for mental health. Primary care companion to the Journal of clinical psychiatry. 2006; 8(2), 106. 
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