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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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“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].”
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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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BackgroundMethionine increases BDNF DNA methylation and improves memory in epilepsy
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MethodGunnar, M. R., Wenner, J. A., Thomas, K. M., Glatt, C. E., McKenna, M. C., & Clark, A. G. (2012) · Development and Psychopathology · doi:10.1017/s095457941200065x · Cited by 55
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Self-citationThe elusive engram: what can infantile amnesia tell us about memory?
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Neurodevelopmental origins of abnormal cortical morphology in dissociative identity disorder
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“Altered stress reactivity following childhood trauma is related to altered gene expression (7), thus suggesting that early life stressors may have long-lasting detrimental effects on neurobiology and foster development of trauma-related psychopathology (8) such as DID.”
BackgroundInfluentialThomas, M., Knoblich, N., Wallisch, A., Glowacz, K., Becker-Sadzio, J., Gundel, F., Brückmann, C., & Nieratschker, V. (2018) · Clinical Epigenetics · doi:10.1186/s13148-018-0544-6 · Cited by 51
“[26] report increased methylation of the BDNF gene in the prefrontal cortex of rats exposed to abusive mothers.”
BackgroundEpigenetic mechanisms impacted by chronic stress across the rodent lifespan
Dion, A., Muñoz, P., & Franklin, T. B. (2022) · Neurobiology of Stress · doi:10.1016/j.ynstr.2022.100434 · Cited by 54
“Maternal or paternal ELS can additionally lead to the inheritance of behavioral phenotypes related to susceptibility and resilience to stress in the offspring (Coley et al., 2019; Franklin et al., 2010; Gapp et al., 2016, 2014; Rodgers et al., 2013; Roth et al., 2009; Weiss et al., 2011).”
Trans-generational Effects of Early Life Stress: The Role of Maternal Behavior
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“4) and the F2 progenies of non-treated and theophylline-treated IMS mothers (ANOVA, F(2,16) 5 11.”
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“…functions in the development of the nervous system and in brain plasticity-related processes such as memory, learning (Aid et al., 2007), and drug addiction, and it may play a role in the regulation of stress response (Roth et al., 2009) and in the biology of mood disorder (Aid et al., 2007).”
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“There is a growing acceptance that the overall epigenetic status of a cell (epigenome) can be modulated by a variety of environmental factors, including nutrients, chemicals and the early-life environment (Weaver et al., 2004; Waterland et al., 2006; Roth et al., 2009).”
BackgroundJarome, T. J., Butler, A. A., Nichols, J. N., Pacheco, N. L., & Lubin, F. D. (2015) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2015.00054 · Cited by 52
“Of the epigenetic mechanisms identified, DNA methylation Frontiers in Molecular Neuroscience | www.frontiersin.org 1 September 2015 | Volume 8 | Article 54 has become particularly attractive due to its potential to regulate gene expression across the lifespan (Roth et al., 2009).”
BackgroundMethodSelf-citationThe Intergenerational Effects of Early Adversity
Galler, J. R., & Rabinowitz, D. G. (2014) · Progress in molecular biology and translational science · doi:10.1016/b978-0-12-800977-2.00007-3 · Cited by 53
“The maternal abuse during early development led to poor mothering in the exposed female offspring when they reared their own young; crossfostering to healthy mothers did not fully reverse these changes in methylation levels [96].”
BackgroundMethodMoore, D. S. (2016) · WIREs Systems Biology and Medicine · doi:10.1002/wsbm.1333 · Cited by 55
“Subsequent work with rodents revealed similar epigenetic effects of early experiences on other DNA segments in other brain areas as well.(19,20) Analogous effects occur in humans and other primates.”
BackgroundBlaze, J., Asok, A., & Roth, T. L. (2015) · Stress · doi:10.3109/10253890.2015.1071790 · Cited by 52
“…polymerase chain reaction (RT-PCR) To amplify immunoprecipitated DNA specific to our candidate genes, we used primers specific to the same or nearby region of the bdnf and reelin genes as we have previously used for DNA methylation studies (Blaze et al., 2013; Roth et al., 2009, 2014) (Figure 2).”
InfluentialSelf-citationPrinciples Governing DNA Methylation during Neuronal Lineage and Subtype Specification
Sharma, A., Klein, S. L., Barboza, L., Lodhi, N., & Tóth, M. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.4037-15.2016 · Cited by 48
“Additional methylation datasets were downloaded from the UCSC genome browser DNA methylation track hub (Seisenberger et al., 2012; Smith et al., 2012; Song et al., 2013).”
MethodDynamic DNA methylation controls glutamate receptor trafficking and synaptic scaling
Sweatt, J. D. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13564 · Cited by 52
Self-citationSteiger, H., & Thaler, L. (2016) · Physiology & Behavior · doi:10.1016/j.physbeh.2016.01.041 · Cited by 52
BDNF-TrkB signalling in fear learning: from genetics to neural networks
Musumeci, G., & Minichiello, L. (2011) · Reviews in the Neurosciences · doi:10.1515/rns.2011.031 · Cited by 51
“In addition, altered methylation patterns of the Bdnf promoter region have been detected in animals that have undergone chronic early post-natal maltreatment (Roth et al. , 2009 ).”
BackgroundDNA methylation profiles in red blood cells of adult hens correlate with their rearing conditions
Pértille, F., Brantsæter, M., Nordgreen, J., Coutinho, L. L., Janczak, A. M., Jensen, P., & Guerrero‐Bosagna, C. (2017) · Journal of Experimental Biology · doi:10.1242/jeb.157891 · Cited by 54
“For example, infant rats exposed to parental maltreatment present long-term DNA methylation and gene expression changes in the brain-derived neurotrophic factor (BDNF) gene in the frontal cortex (Roth et al., 2009).”
BackgroundEpigenetic Basis for the Development of Depression in Children
Lester, B. M., Conradt, E. D., & Marsit, C. J. (2013) · Clinical Obstetrics & Gynecology · doi:10.1097/grf.0b013e318299d2a8 · Cited by 50
“There were also deficits in BDNF gene expression that persisted into adulthood and the following generation.(34) There was greater methylation of BDNF among offspring of maltreated rodents, even among offspring who were cross-fostered and raised by mothers who had never been maltreated.”
BackgroundNeurodevelopment and ages of onset in depressive disorders
Hagan, C. C., Graham, J. M. E., Wilkinson, P. O., Midgley, N., Suckling, J., Sahakian, B. J., & Goodyer, I. M. (2015) · The Lancet Psychiatry · doi:10.1016/s2215-0366(15)00362-4 · Cited by 46
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“In some cases, stress effects on expression of specific genes have been demonstrated, for example, the estrogen receptor ERα i [20], and BDNF, a gene involved in many different neural processes [21].”
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Zucchi, F. C. R., Yao, Y., & Metz, G. A. S. (2012) · Frontiers in Genetics · doi:10.3389/fgene.2012.00096 · Cited by 51
“This behavioral phenotype is linked to hypermethylation of the BDNF gene and consequently low expression of BDNF in the prefrontal cortex of offspring (Roth et al., 2009).”
BackgroundEpigenetics and the Social Work Imperative
Combs-Orme, T. D. (2012) · Social Work · doi:10.1093/sw/sws052 · Cited by 48
Early-life stress interactions with the epigenome
Lewis, C. R., & Olive, M. F. (2014) · Behavioural Pharmacology · doi:10.1097/fbp.0000000000000057 · Cited by 53
“A third, more recently developed ELS paradigm, pioneered by Roth et al. (2009), exposed pups to a stressed female who showed abusive behaviors (discussed in more detail below).”
BackgroundMethodInfluentialMaternal separation in rodents: a journey from gut to brain and nutritional perspectives
Rincel, M., & Darnaudéry, M. (2019) · Proceedings of The Nutrition Society · doi:10.1017/s0029665119000958 · Cited by 51
The state of the science on trauma inquiry
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Callaghan, B. L., Graham, B. M., Li, S., & Richardson, R. (2013) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2013.00090 · Cited by 50
“In addition, epigenetic modifications to gene transcription caused by early life stress have been shown to persist across the life of the rat and to be passed onto biological offspring (137).”
BackgroundBrain‐derived neurotrophic factor and inflammatory markers in school‐aged children with early trauma
Bücker, J., Fries, G. R., Kapczinski, F. P., Post, R. M., Yatham, L. N., Vianna, P., Chies, J. A. B., Gama, C. S., Magalhães, P. V. D. S., de Aguiar, B. W., et al. (2014) · Acta Psychiatrica Scandinavica · doi:10.1111/acps.12358 · Cited by 49
“A growing body of evidence suggests that stress and traumatic events may have effects on BDNF expression through the modulation of epigenetic mechanisms, including DNA methylation and histone modifications (14, 34).”
BackgroundPost, R. M., Altshuler, L. L., Kupka, R., McElroy, S. L., Frye, M. A., Rowe, M., Grunze, H., Suppes, T. M., Keck, P. E., Leverich, G. S., et al. (2016) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2016.06.008 · Cited by 50
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Caregiver maltreatment causes altered neuronal DNA methylation in female rodents
Blaze, J., & Roth, T. L. (2017) · Development and Psychopathology · doi:10.1017/s0954579417000128 · Cited by 48
“We performed caregiving manipulations using a well-established protocol previously reported in our laboratory (Asok, Bernard, Rosen, Dozier, & Roth, 2014; Blaze et al., 2013, 2015; Blaze & Roth, 2013; Roth et al., 2009, 2014) and adapted from others (Ivy et al., 2008; Roth & Sullivan, 2005).”
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“Finally, is important to take into account that chronically stressed caregivers, as the pregnant mothers, may display abusive behaviors to the infants, leading to epigenetic alterations in the mPFC that persist to adulthood (Moore and Power 1986; Roth et al. 2009).”
BackgroundImpaired one carbon metabolism and DNA methylation in alcohol toxicity
Kruman, I. I., & Fowler, A. (2014) · Journal of Neurochemistry · doi:10.1111/jnc.12677 · Cited by 48
Abbs, B., Liang, L., Makris, N., Tsuang, M. T., Seidman, L. J., & Goldstein, J. M. (2011) · NeuroImage · doi:10.1016/j.neuroimage.2011.03.079 · Cited by 49
“…of neurotransmitters, such as GABA and glutamate, and growth factors, such as brain derived neurotrophic factor, both of which can cause structural changes to memory-related brain areas (Horner et al., 1990; Kadekaro et al., 1988; Radley et al., 2004; Roth et al., 2009; Virgin et al., 1991).”
BackgroundBrain-derived neurotrophic factor and early-life stress: Multifaceted interplay
Bondar, N. P., & Merkulova, T. I. (2016) · Journal of Biosciences · doi:10.1007/s12038-016-9648-3 · Cited by 48
“Female rats that were subjected to postnatal stress have less histone H3K9/14 acetylation associated with Bdnf IV DNA in the mPFC (Blaze et al. 2015).”
BackgroundBlaze, J., Asok, A., Borrelli, K. N., Tulbert, C. D., Bollinger, J. L., Ronca, A. E., & Roth, T. L. (2017) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2017.03.007 · Cited by 54
“For methylation assays, DNA was bisulfite-converted (Epitect Bisulfite Kit, Qiagen, Inc., Valencia, CA) and direct bisulfite-sequencing PCR (BSP) was used to measure methylation at 11 CG sites in Bdnf exon IV as previously reported (Roth et al., 2009; Roth et al., 2014).”
BackgroundMethodInfluentialSelf-citationDoherty, T. S., Blaze, J., Keller, S. M., & Roth, T. L. (2017) · Developmental Psychobiology · doi:10.1002/dev.21547 · Cited by 50
“Our lab has previously identified the impact of these brief and repeated exposures on one realm of behavior, maternal behavior (Roth et al., 2009), as well as the epigenome in several brain areas of adolescent and adult animals (Blaze, Asok, & Roth, 2015; Blaze & Roth, 2013; Blaze, Scheuing, &…”
Self-citationLi, X., Lv, Q., Tang, W., Deng, W., Zhao, L., Meng, Y., Guo, W., & Li, T. (2020) · Journal of Affective Disorders · doi:10.1016/j.jad.2020.12.126 · Cited by 50
“In present study, we found that exposure to all types of the ELA is correlated with anxiety and depression, and the long-lasting effects of exposure to multiple types of ELA or recurring ELA increase the risks for anxiety and depression, which is in line with previous studies (Roth et al., 2009).”
ResultSoga, T., Teo, C. H., & Parhar, I. S. (2021) · Frontiers in Genetics · doi:10.3389/fgene.2020.601868 · Cited by 47
Wojcicki, J. M., Heyman, M. B., Elwan, D., Shiboski, S., Lin, J., Blackburn, E., & Epel, E. (2015) · Translational Psychiatry · doi:10.1038/tp.2015.71 · Cited by 44
Gene-Environment Interactions and Role of Epigenetics in Anxiety Disorders
Lin, E., & Tsai, S. (2020) · Advances in experimental medicine and biology · doi:10.1007/978-981-32-9705-0_6 · Cited by 51
Epigenetic Changes Associated with Different Types of Stressors and Suicide
Dee, G., Ryznar, R. J., & Dee, C. (2023) · Cells · doi:10.3390/cells12091258 · Cited by 51
“Similar to the conflicting results reported for FKBP5, epigenetic changes in BDNF (brain-derived neurotrophic factor) with childhood stress show the hypermethylation of either the BDNF promoter/coding region [63], hypomethylation [64], hypomethylation [64], or no association of methylation changes with stress [65].”
ResultEpigenetic regulation of brain development, plasticity, and response to early-life stress
Peña, C. J. (2025) · Neuropsychopharmacology · doi:10.1038/s41386-025-02179-z · Cited by 56
“…decreases mRNA expression of Bdnf exons IV and/or IX in prefrontal cortex, ventral tegmental area (VTA), and hippocampus, which is mediated by increased DNA methylation and decreased histone acetylation, and reversed by treatment with a DNA methylation inhibitor or antidepressants [121 – 123].”
Wang, Q., Shao, F., & Wang, W. (2015) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2015.00049 · Cited by 48
“Roth et al. (2009) demonstrated that early maltreatment increased the methylation of BDNF DNA and it reduced the BDNF expression in PFC of adult rats.”
BackgroundAn integrated biopsychosocial model of childhood maltreatment and psychosis
Barker, V., Gumley, A. I., Schwannauer, M., & Lawrie, S. M. (2015) · The British Journal of Psychiatry · doi:10.1192/bjp.bp.113.143578 · Cited by 53
Different stress-related gene expression in depression and suicide
Zhao, J., Qi, X., Gao, S., Lu, J., van Wamelen, D. J., Kamphuis, W., Bao, A., & Swaab, D. F. (2015) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2015.06.010 · Cited by 46
“Their decreased expression correlated with hypermethylation of the BDNF promoters in exons 4 and 9 (Roth et al., 2009).”
BackgroundParent–offspring transaction: Mechanisms and the value of within family designs
Jenkins, J. M., McGowan, P. O., & Knafo‐Noam, A. (2015) · Hormones and Behavior · doi:10.1016/j.yhbeh.2015.06.018 · Cited by 47
“Indeed, epigenetic changes associated with maternal care were subsequently shown to be widespread, influencing many other genes implicated in neuroplasticity and stress-related processes (McGowan et al., 2011; Murgatroyd et al., 2009; Roth et al., 2009).”
Dezsi, G., Öztürk, E., Salzberg, M. R., Morris, M. J., O'Brien, T. J., & Jones, N. C. (2016) · Neurobiology of Disease · doi:10.1016/j.nbd.2016.05.005 · Cited by 45
Hsieh, M.-T., Lin, C.-C., Lee, C., & Huang, T. (2019) · Journal of Clinical Medicine · doi:10.3390/jcm8050568 · Cited by 47
“However, data on the CpG sites near rs6265 (equivalent to the G196A or Val66Met polymorphism) in the BDNF region in peripheral blood has not been studied before, especially at BDNF exon IX (coding exon) [30,38].”
BackgroundMenezes, J., Souto das Neves, B.-H., Gonçalves, R., Benetti, F., & Mello-Carpes, P. B. (2020) · Behavioural Brain Research · doi:10.1016/j.bbr.2020.112468 · Cited by 46
Stress-Related Programming of Autonomic Imbalance: Role in Allergy and Asthma
Wright, R. J. (2012) · Chemical immunology/Fortschritte der Allergielehre/Progress in allergy/Chemical immunology and allergy · doi:10.1159/000336496 · Cited by 45
Post, R. M., Leverich, G. S., Kupka, R., Keck, P. E., McElroy, S. L., Altshuler, L. L., Frye, M. A., Luckenbaugh, D. A., Rowe, M., Grunze, H., et al. (2013) · Acta Psychiatrica Scandinavica · doi:10.1111/acps.12208 · Cited by 44
“Recent data have even suggested the possibility that some of these epigenetic marks could be transmitted across generations independent of the repetition of adverse behavioral experiences, yielding another potential transgenerational epigenetic mechanism for increased illness vulnerability in the face of both parents…”
BackgroundHori, N., Narita, M., Yamashita, A., Horiuchi, H., Hamada, Y., Kondo, T., Watanabe, M., Igarashi, K., Kawata, M., Shibasaki, M., et al. (2016) · Synapse · doi:10.1002/syn.21902 · Cited by 45
“, 2009), and in association with a mental disorder (Murgatroyd et al., 2009; Roth et al., 2009).”
BackgroundBorges, J. V., de Freitas, B. S., Antoniazzi, V., dos Santos, C. D. S., Vedovelli, K., Pires, V. N., Paludo, L., de Lima, M. N. M., & Bromberg, E. (2019) · Behavioural Brain Research · doi:10.1016/j.bbr.2019.03.025 · Cited by 45
Social Inequalities and the Road to Allostatic Load: From Vulnerability to Resilience
Juster, R., Seeman, T. E., McEwen, B. S., Picard, M. A., Mahar, I., Mechawar, N., Sindi, S., Smith, N. G., Souza‐Talarico, J. N., Sarnyai, Z., et al. (2016) · Wiley eBooks · doi:10.1002/9781119125556.devpsy408 · Cited by 46
Fuentes, S., Daviu, N., Gagliano, H., Garrido, P., Zelena, D., Monasterio, N., Armario, A., & Nadal, R. A. (2014) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2014.00056 · Cited by 47
“Because expected to observe some type of maltreatment, the following behavioral patterns were measured (time and frequency): stepping on the pups, dropping them, dragging them, actively avoiding/pushingaway, and rough-handling (see Roth et al., 2009).”
BackgroundResultInfluentialAdvancing Neuroscience Through Epigenetics: Molecular Mechanisms of Learning and Memory
Molfese, D. L. (2011) · Developmental Neuropsychology · doi:10.1080/87565641.2011.606395 · Cited by 45
“Roth and colleagues created a stressful environment for rat mothers who then were more likely to abuse or neglect their pups ( Roth, Lubin, Funk, & Sweatt, 2009 ).”
BackgroundLewis, C. R., Breitenstein, R. S., Henderson-Smith, A., Sowards, H., Piras, I. S., Huentelman, M. J., Doane, L. D., & Lemery‐Chalfant, K. (2020) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-020-00885-4 · Cited by 45
An Improved CRISPR/dCas9 Interference Tool for Neuronal Gene Suppression
Duke, C. G., Bach, S. V., Revanna, J. S., Sultan, F. A., Southern, N. T., Davis, M. N., Carullo, N. V. N., Bauman, A. J., Phillips, R. A., & Day, J. J. (2020) · Frontiers in Genome Editing · doi:10.3389/fgeed.2020.00009 · Cited by 40
Moshe Szyf, A. (2013) · The Canadian Journal of Psychiatry · doi:10.1177/070674371305801208 · Cited by 43
Calabrese, F., Luoni, A., Guidotti, G., Racagni, G., Fumagalli, F., & Riva, M. A. (2013) · Psychopharmacology · doi:10.1007/s00213-012-2900-0 · Cited by 43
“…treatment with lurasidone and valproate, alone or in combination, and considering that the BDNF gene may be regulated through epigenetic mechanisms (Roth et al. 2009a; Tsankova et al. 2006), we decided to investigate the gene expression of three histone deacetylases (HDAC 1, 2, and 5) that play a…”
BackgroundJiao, J., Opal, M. D., & Dulawa, S. C. (2012) · Molecular Psychiatry · doi:10.1038/mp.2012.136 · Cited by 44
Maternal care associates with play dominance rank among adult female rats
Parent, C. I., Corpo, A. D., Cameron, N. M., & Meaney, M. J. (2012) · Developmental Psychobiology · doi:10.1002/dev.21070 · Cited by 45
Genipin normalizes depression-like behavior induced by prenatal stress through inhibiting DNMT1
Ye, D., Zhang, L., Fan, W., Zhang, X., & Dong, E. (2018) · Epigenetics · doi:10.1080/15592294.2018.1450033 · Cited by 44
Intergenerational Transmission of Child Abuse and Neglect: A Transdisciplinary Analysis
Wert, M. V., Anreiter, I., Fallon, B., & Sokolowski, M. B. (2019) · Gender and the Genome · doi:10.1177/2470289719826101 · Cited by 54
(2013) · PubMed · Cited by 43
The importance of epigenetics in diagnostics and treatment of major depressive disorder
Czarny, P., Białek, K., Ziółkowska, S., Strycharz, J., Barszczewska, G., & Sliwinski, T. (2021) · Journal of Personalized Medicine · doi:10.3390/jpm11030167 · Cited by 37
Jiang, Z., Zhu, Z., Zhao, M., Wang, W., Li, H., Liu, D., & Pan, F. (2021) · Psychopharmacology · doi:10.1007/s00213-021-05896-7 · Cited by 43
Early experiences: Building up the tools to face the challenges of adult life
Branchi, I., & Cirulli, F. (2014) · Developmental Psychobiology · doi:10.1002/dev.21235 · Cited by 43
Epigenetic Regulation of Infant Neurobehavioral Outcomes
Lesseur, C., Paquette, A. G., & Marsit, C. J. (2014) · Medical Epigenetics · doi:10.1159/000361026 · Cited by 46
Cutuli, D., Caporali, P., Gelfo, F., Angelucci, F., Laricchiuta, D., Foti, F., Bartolo, P. D., Bisicchia, E., Molinari, M., Vecchioli, S. F., et al. (2015) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2015.00066 · Cited by 43
“The expression of offspring neurotrophins is modified by early experiences, either negative (i.e., maternal maltreatment) or positive (i.e., environmental enrichment) (Sale et al., 2004; Roth et al., 2009; Caporali et al., 2014).”
BackgroundInflammatory markers and suicidal attempts in depressed patients: A review
Marini, S., Vellante, F., Matarazzo, I., Berardis, D. D., Serroni, N., Gianfelice, D., Olivieri, L., Renzo, F. D., Marco, A. D., Fornaro, M., et al. (2016) · International Journal of Immunopathology and Pharmacology · doi:10.1177/0394632015623793 · Cited by 42
Zhang, Z.-Y., Mao, Y., Feng, X., Zheng, N., Lü, L., Ma, Y., Qin, D., & Hu, X. (2016) · Behavioural Brain Research · doi:10.1016/j.bbr.2016.03.040 · Cited by 44
McCoy, C. R., Rana, S., Stringfellow, S. A., Day, J. J., Wyss, J. M., Clinton, S. M., & Kerman, I. A. (2016) · European Journal of Neuroscience · doi:10.1111/ejn.13404 · Cited by 46
“Environmental factors and various life experiences modify DNA methylation and other epigenetic processes in a variety of tissues, including the brain (McGowan et al., 2008; McGowan et al., 2009; Murgatroyd et al., 2009; Roth et al., 2009; LaSalle, 2011; Franklin et al., 2012; Naumova et al., 2012; Klengel et al., 2014…”
Hoye, J. R., Cheishvili, D., Yarger, H. A., Roth, T. L., Szyf, M., & Dozier, M. (2019) · Development and Psychopathology · doi:10.1017/s0954579419001421 · Cited by 44
“For example, cross-fostering rat offspring to high quality maternal care can reverse the methylation patterns that are associated with low quality maternal care or maltreatment (Roth et al., 2009; Weaver et al., 2004).”
BackgroundSelf-citationWhat’s in a name? The three genealogies of the social in social epigenetics
Louvel, S. (2020) · Social Science Information · doi:10.1177/0539018419897001 · Cited by 40
“Ultimately, they aim to design pharmaceutical interventions to rescue aberrant gene expression due to early-life adversity (Roth et al., 2009).”
BackgroundEarly Life Stress and Metabolic Plasticity of Brain Cells: Impact on Neurogenesis and Angiogenesis
Salmina, A. B., Gorina, Y. V., Komleva, Y. K., Panina, Y. A., Malinovskaya, N. A., & Lopatina, O. L. (2021) · Biomedicines · doi:10.3390/biomedicines9091092 · Cited by 42
“Methylation of BDNF gene was found to be altered in the prefrontal cortex of mice exposed to ELS [126].”
BackgroundBy what molecular mechanisms do social determinants impact cardiometabolic risk?
Baumer, Y., Pita, M. A., Baez, A. S., Ortiz-Whittingham, L. R., Cintron, M., Rose, R., Gray, V. C., Baah, F. O., & Powell‐Wiley, T. M. (2023) · Clinical Science · doi:10.1042/cs20220304 · Cited by 40
“Additionally, mouse models demonstrate that parental abuse results in increased methylation of BDNF genes that both persist into adulthood and are seen in the offspring of the maltreated mice [230].”
Environmental Alterations of Epigenetics Prior to the Birth
Lo, C., & Zhou, F. (2014) · International review of neurobiology · doi:10.1016/b978-0-12-801311-3.00001-9 · Cited by 44
“For example, increased miR-16 expression (Bai et al., 2012) and increased promoter DNA methylation of BDNF (Roth et al., 2009) were found in separate studies, but both changes result in a reduction in BDNF mRNA expression, suggesting BDNF may play a role in regulating offspring behavior in response…”
BackgroundInfluentialAntistress properties of antidepressant drugs and their clinical implications
Calabrese, F., Molteni, R., & Riva, M. A. (2011) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2011.05.007 · Cited by 42
Gavin, D. P., & Akbarian, S. (2011) · Neurobiology of Disease · doi:10.1016/j.nbd.2011.12.008 · Cited by 42
Caporali, P., Cutuli, D., Gelfo, F., Laricchiuta, D., Foti, F., Bartolo, P. D., Mancini, L., Angelucci, F., & Petrosini, L. (2014) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2014.00195 · Cited by 40
“…did not influence neurotrophin levels in neocortical and hippocampal regions, despite the high sensitivity of these regions to parental experiences (Arai et al., 2009; Roth et al., 2009; Mychasiuk et al., 2012) and environmental enrichment (Pham et al., 1999, 2002; Angelucci et al., 2009).”
BackgroundGleason, E. D., & Marler, C. A. (2013) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.2013.0824 · Cited by 41
“Likewise, some models of maternal abuse in rodents show that stressed mothers tend to drag, grab, or roughly handle pups more than non-stressed mothers, suggesting that the behaviour of a stressed parent may resemble that of an abusive one [31].”
BackgroundPeng, H.-H., Tsai, T.-C., Huang, W.-Y., Wu, H.-M., & Hsu, K. (2019) · Neuropharmacology · doi:10.1016/j.neuropharm.2019.04.026 · Cited by 41
Effect of Early Life Stress on the Epigenetic Profiles in Depression
Li, M., Fu, X., Xie, W., Guo, W., Li, B., Cui, R., & Yang, W. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00867 · Cited by 41
“On the other hand, ELS caused epigenetic changes in the HPA axis, serotonin, dopamine, and some neuropeptides (McGowan et al., 2009; Roth et al., 2009; Bai et al., 2012; Kang et al., 2013; Ouellet-Morin et al., 2013; Zhang et al., 2015; Bahi, 2016; Bustamante et al., 2016; Tyrka et al., 2016; Williams et al., 2016; Wa…”
BackgroundNeuronal epigenetics and the aging synapse
Azpurua, J., & Eaton, B. A. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00208 · Cited by 39
“Recent studies have found that BDNF methylation is be required for fear memory consolidation, and can be altered in early life in mice by events such as early weaning or isolation (Lubin et al., 2008; Roth et al., 2009).”
BackgroundKim, J., Stewart, R. J., Kang, H., Bae, K., Kim, S., Shin, I., Hong, Y. J., Ahn, Y., Jeong, M. H., & Yoon, J. (2015) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2015.08.013 · Cited by 41
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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