DNA Epigenetics in Addiction Susceptibility
Open accessAbstract
Addiction is a chronically relapsing neuropsychiatric disease that occurs in some, but not all, individuals who use substances of abuse. Relatively little is known about the mechanisms which contribute to individual differences in susceptibility to addiction. Neural gene expression regulation underlies the pathogenesis of addiction, which is mediated by epigenetic mechanisms, such as DNA modifications. A growing body of work has demonstrated distinct DNA epigenetic signatures in brain reward regions that may be associated with addiction susceptibility. Furthermore, factors that influence addiction susceptibility are also known to have a DNA epigenetic basis. In the present review, we discuss the notion that addiction susceptibility has an underlying DNA epigenetic basis. We focus on major phenotypes of addiction susceptibility and review evidence of cell type-specific, time dependent, and sex biased effects of drug use. We highlight the role of DNA epigenetics in these diverse processes and propose its contribution to addiction susceptibility differences. Given the prevalence and lack of effective treatments for addiction, elucidating the DNA epigenetic mechanism of addiction vulnerability may represent an expeditious approach to relieving the addiction disease burden.
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Epigenetic modifications are likely to have particularly long-lasting consequences to the brain when they occur during fetal or early infancy stages.
“Epigenetic modifications are likely to have particularly long- lasting consequences to the brain when they occur during fetal or early infancy stages.”
From Substance use disorders: a comprehensive update of classification, epidemiology, neurobiology, clinical aspects, treatment and prevention (2023) · cites this paper as [113]
The ‘DNA Modifications in Neural Development and Ageing’ section says DNA modifications regulate prenatal and postnatal brain development and describes some early-life modification patterns as stable across development. The ‘Addiction Susceptibility and Brain Development’ section reports lasting effects of prenatal and early-life drug exposure. Neither passage establishes that epigenetic modifications occurring at fetal or early-infancy stages have particularly long-lasting brain consequences compared with modifications at other stages; page numbers are unavailable in our copy. (LLM, conf=0.78)
Experimental — accuracy not yet measuredClinical studies based on blood cells have found that individuals who consume drugs show epigenetic changes that appear to relate to the frequency of use in a dose-dependent manner.
“Clinical studies based on blood cells have found that individuals who consume drugs show epigenetic changes that appear to relate to the frequency of use in a dose- dependent man ner 113 .”
From Substance use disorders: a comprehensive update of classification, epidemiology, neurobiology, clinical aspects, treatment and prevention (2023) · cites this paper as [113]
The section on sex differences in DNA modifications (page unavailable) reports altered blood DNA methylation in men with alcoholism and a positive correlation between recent alcohol-use history and methylation in lymphocyte-derived cells from women. It does not establish that methylation changes track the frequency of drug use in a dose-dependent manner across drugs or individuals who use them. (LLM, conf=0.84)
Experimental — accuracy not yet measuredThe enzymes mediating epigenetic modifications play a fundamental role in embryonic and postnatal brain development, so their modification with in utero or early postnatal exposure to drugs might contribute to a higher vulnerability to addiction later in life.
“This is because the enzymes mediat ing epigenetic modifications play a fundamental role in embry onic and postnatal brain development, so that their modification with in utero or early postnatal exposure to drugs might contrib ute to a higher vulnerability to addiction later in life 113 .”
From Substance use disorders: a comprehensive update of classification, epidemiology, neurobiology, clinical aspects, treatment and prevention (2023) · cites this paper as [113]
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References 235 · Cited by 34
Research works printed but not linked: 1
- National Center for Chronic Disease Prevention and Health Promotion (2012). “ Reports of the Surgeon General,” in Preventing Tobacco Use Among Youth and Young Adults: A Report of the Surgeon General. Atlanta (GA): Centers for Disease Control and Prevention US. 22876391
- Authors
- Kaplan, G., Xu, H., Abreu, K., & Feng, J.
- Affiliations
- Florida State University (US)
- Corresponding author
- Feng, Jian
- Venue
- Frontiers in Genetics
- Publisher
- Frontiers Media SA
- Published
- 2022-01-25
- Volume
- 13
- Pages
- 806685-806685
- ISSN
- 1664-8021 (ISSN-L)
- PMC
- PMC8821887
- OpenAlex
- W4210333879
- Cited by
- 34
- References
- 235
- Citations by year
- 2026: 7 · 2025: 12 · 2024: 7 · 2023: 5 · 2022: 3
- FWCI
- 0.70
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Genetics (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institute on Drug Abuse (DP1DA046587 R01DA046720)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Keywords
- addiction vulnerability, substance use disorders, individual differences, sex differences, relapse
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