The DOI matches its Crossref record; 75 of the 75 references it cites were found in a registry or an index.
Lasting Epigenetic Influence of Early-Life Adversity on the BDNF Gene
Open accessAbstract
Background Childhood maltreatment and early trauma leave lasting imprints on neural mechanisms of cognition and emotion. Using a rat model of infant maltreatment by a caregiver, we investigated whether early-life adversity leaves lasting epigenetic marks at the Brain-derived Neurotrophic Factor (BDNF) gene in the CNS. Methods During the first postnatal week, we exposed infant rats to stressed caretakers that predominately displayed abusive behaviors. We then assessed DNA methylation patterns and gene expression throughout the life span, as well as DNA methylation patterns in the next generation of infants. Results Early maltreatment produced persisting changes in methylation of BDNF DNA that caused altered BDNF gene expression in the adult prefrontal cortex. Furthermore, we observed altered BDNF DNA methylation in offspring of females that had previously experienced the maltreatment regimen. Conclusions These results highlight an epigenetic molecular mechanism potentially underlying lifelong and transgenerational perpetuation of changes in gene expression and behavior incited by early abuse and neglect.
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“Furthermore, the findings suggested germ-line inheritance because cross-fostering could not completely erase these DNA methylation changes.”
From Biological Embedding of Early-Life Adversity and a Scoping Review of the Evidence for Intergenerational Epigenetic Transmission of Stress and Trauma in Humans (2023) · cites this paper as [73]
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“ELS results in hippocampal hypermethylation at the promoter regions of genes related to the stress axis and brain development, including glucocorticoid receptor (NR3c1) region 17 29–31 and brain derived neurotrophic factor (BDNF) region IV32–34.”
From Maternal and Early-Life Circadian Disruption Have Long-Lasting Negative Consequences on Offspring Development and Adult Behavior in Mice (2017) · cites this paper as [32]
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“Other animal findings also suggested ELS/CT-related epigenetic changes in the CNS growth and differentiation-related BDNF gene expression (407), while in a genome-wide blood DNA methylation analysis study by Houtepen et al. (408), a locus in the Kit ligand gene (KITLG;”
From Developmental Trajectories of Early Life Stress and Trauma: A Narrative Review on Neurobiological Aspects Beyond Stress System Dysregulation (2019) · cites this paper as [407]
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“Early-life maltreatment of infant rats produced persistent changes in Bdnf DNA methylation that were passed to the next generation by maltreated mothers [73].”
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“Infant maltreatment increases DNA methylation and reduces BDNF gene expression in the PFC (191).”
From A brain-centric model of suicidal behavior (2020) · cites this paper as [191]
In the citing paper
“Differential levels of DNA methylation of genes related to stress reactivity have already been associated with PTSD and early life stress [93-95].”
From Efficacy of oxytocin administration early after psychotrauma in preventing the development of PTSD: study protocol of a randomized controlled trial (2014) · cites this paper as [94]
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“In a related study, adult rats exposed to mistreatment at an early age exhibited higher levels of DNA methylation at CpG sites within the Bdnf promoter as well as decreased levels of Bdnf mRNA.”
From Epigenetic mechanisms of major depression: Targeting neuronal plasticity (2018) · cites this paper as [124]
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“as compared to average reported increases for the same regions resulting from early-life stress of 95%32–34 and 135%29, 30, 47, respectively”
From Maternal and Early-Life Circadian Disruption Have Long-Lasting Negative Consequences on Offspring Development and Adult Behavior in Mice (2017) · cites this paper as [32]
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Citations
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MeCP2, a Key Contributor to Neurological Disease, Activates and Represses Transcription
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The neurobiological consequences of early stress and childhood maltreatment
Teicher, M. H., Andersen, S. L., Polcari, A., Anderson, C. M., Navalta, C. P., & Kim, D. M. (2003) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(03)00007-1 · Cited by 1,465
Cited by
Sorted by citations
The Lifelong Effects of Early Childhood Adversity and Toxic Stress
Shonkoff, J. P., Garner, A. S., THE COMMITTEE ON PSYCHOSOCIAL ASPECTS OF CHILD AND FAMILY HEALTH, C. O. E. C., Siegel, B. S., Dobbins, M. I., Earls, M. F., Garner, A. S., McGuinn, L., Pascoe, J., & Wood, D. L. (2012) · Pediatrics · doi:10.1542/peds.2011-2663 · Cited by 5,164
Suicide and suicidal behaviour
Turecki, G., & Brent, D. A. (2016) · The Lancet · doi:10.1016/s0140-6736(15)00234-2 · Cited by 2,338
Socioeconomic status and the brain: mechanistic insights from human and animal research
Hackman, D. A., Farah, M. J., & Meaney, M. J. (2010) · Nature Reviews Neuroscience · doi:10.1038/nrn2897 · Cited by 1,409
Parental olfactory experience influences behavior and neural structure in subsequent generations
Dias, B. G., & Ressler, K. J. (2014) · Nature Neuroscience · doi:10.1038/nn.3594 · Cited by 1,338
Epigenetics and the biological definition of gene×environment interactions
Meaney, M. J. (2010) · Child Development · doi:10.1111/j.1467-8624.2009.01381.x · Cited by 1,239
“Manipulations that alter mother–pup interactions in the rat alter patterns of gene expression and stress response in the offspring (e.g., Francis et al., 1999; Meaney, 2001; Roth et al., 2009; Toki et al., 2007).”
Background
Metadata
- Authors
- Roth, T. L., Lubin, F. D., Funk, A. J., & Sweatt, J. D.
- Affiliations
- University of Alabama (US)
- University of Alabama at Birmingham (US)
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2009-05
- Volume
- 65
- Issue
- 9
- Pages
- 760-769
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC3056389
- OpenAlex
- W1965636455
- Semantic Scholar
- 73b25ed907cfc11b7dfd5f2e6c7e3f05afbe7148
- Cited by
- 1,273
- References
- 75
- Citations by year
- 2026: 26 · 2025: 27 · 2024: 37 · 2023: 38 · 2022: 39 · 2021: 68 · 2020: 78 · 2019: 77 · 2018: 90 · 2017: 91 · 2016: 107 · 2015: 100 · 2014: 145 · 2013: 105 · 2012: 91
- FWCI
- 86.14
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (R01AG031722)
- National Institute of Mental Health (MH 57014, R01MH057014)
- National Institute of Neurological Disorders and Stroke (NS048811, F32NS048811)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- childhood adversity, child abuse, brain-derived neurotrophic factor, DNA methylation, epigenetics, transgenerational transmission, prefrontal cortex, gene expression, infant rat model, caregiver abuse, neglect
- MeSH terms
- Animals, Animals, Newborn, Cytidine, Female, Hippocampus, Injections, Intraventricular, Male, Maternal Behavior, Stress, Psychological, Gene Expression, Prefrontal Cortex, DNA Methylation, Brain-Derived Neurotrophic Factor, Rats, Long-Evans, Models, Animal, Epigenesis, Genetic, Rats
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