Childhood adversity and DNA methylation of genes involved in the hypothalamus-pituitary-adrenal axis and immune system: whole-genome and candidate-gene associations
Open accessAbstract
In recent years, translational research involving humans and animals has uncovered biological and physiological pathways that explain associations between early adverse circumstances and long-term mental and physical health outcomes. In this article, we summarize the human and animal literature demonstrating that epigenetic alterations in key biological systems, the hypothalamus–pituitary–adrenal axis and immune system, may underlie such disparities. We review evidence suggesting that changes in DNA methylation profiles of the genome may be responsible for the alterations in hypothalamus–pituitary–adrenal axis and immune system trajectories. Using some preliminary data, we demonstrate how explorations of genome-wide and candidate-gene DNA methylation profiles may inform hypotheses and guide future research efforts in these areas. We conclude our article by discussing the many important future directions, merging perspectives from developmental psychology, molecular genetics, neuroendocrinology, and immunology, that are essential for furthering our understanding of how early adverse circumstances may shape developmental trajectories, particularly in the areas of stress reactivity and physical or mental health.
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Children with foster care experience show significant differences in methylation in 72 of 173 investigated genes responsible for HPA and immune system regulation compared with children without foster care experience.
“Bick et al. (409) reported significant differences in methylation in 72 of investigated 173 genes (responsible for HPA and immune system regulation) in children with and without foster care experience.”
From Developmental Trajectories of Early Life Stress and Trauma: A Narrative Review on Neurobiological Aspects Beyond Stress System Dysregulation (2019) · cites this paper as [409]
In ‘Early adversity and whole-genome DNA methylation profiles’ (page not provided), the paper reports differences in 173 genes: 72 had higher methylation and 101 had lower methylation in participants with foster-care histories. The claim omits the 101 genes, describes all 173 as regulating the HPA axis and immune system although the paper identifies only some as immune-related, and calls the participants children although they were aged 20–28 when methylation was measured. (LLM, conf=0.90)
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- Authors
- Bick, J., Naumova, O., Hunter, S., Barbot, B., Lee, M., Luthar, S. S., Raefski, A., & Grigorenko, E. L.
- Affiliations
- Yale University (US)
- Lomonosov Moscow State University (RU)
- Corresponding author
- Grigorenko, Elena L.
- Venue
- Development and Psychopathology
- Publisher
- Cambridge University Press (CUP)
- Published
- 2012-10-15
- Volume
- 24
- Issue
- 4
- Pages
- 1417-1425
- ISSN
- 0954-5794 (ISSN-L)
- 1469-2198
- PMC
- PMC3755948
- OpenAlex
- W2132635226
- Semantic Scholar
- 081861ee57911f241f6b53c9632c1adf8e3b880d
- Cited by
- 140
- References
- 80
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 7 · 2023: 14 · 2022: 9 · 2021: 8 · 2020: 9 · 2019: 10 · 2018: 13 · 2017: 18 · 2016: 11 · 2015: 13 · 2014: 10 · 2013: 8
- FWCI
- 0.90
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Development and Psychopathology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (NIHT32 MH18268, T32MH018268)
- National Institute on Drug Abuse (R01DA010726, DA010726, DA11498, R01DA011498, DA14385, R01DA014385)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P50HD052120)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- childhood adversity, DNA methylation, epigenetics, hypothalamic-pituitary-adrenal axis, immune system, stress reactivity, health disparities, candidate gene association, developmental trajectories, mental health, physical health
- MeSH terms
- Animals, Child, Child Abuse, Humans, Hypothalamo-Hypophyseal System, Pituitary-Adrenal System, Stress, Psychological, DNA Methylation, Epigenesis, Genetic, Genome-Wide Association Study, Genetic Association Studies
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