Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse

McGowan, Patrick O.; Sasaki, Aya; D’Alessio, Ana C.; Dymov, Sergiy; Labonté, Benoit; Szyf, Moshe; Turecki, Gustavo; Meaney, Michael J.

doi:10.1038/nn.2270

Cited by 3,036 publications

(2,320 citation statements)

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“…These epigenetic modifications occur without sequential variation. Epigenetic control of gene expression is highly responsive to environmental influences such as ELS, especially during developmentally sensitive periods in early life, as has been shown in rodents (Champagne, 2008; Meaney, 2001; Weaver et al, 2004) and humans (McGowan et al, 2009). DNA methylation, i.e., the attachment of methyl groups (CH 3 ) to the 5-carbon position of cytosine, which typically occurs at so-called CpG dinucleotides where a cytosine base is followed by a guanine base, generally results in gene silencing and is the only epigenetic modification of the human OXTR gene studied to date.…”

Section: Gene-environment Interactions and Epigenetic Modificationmentioning

confidence: 94%

Oxytocin pathways in the intergenerational transmission of maternal early life stress

Toepfer

Heim

Entringer

et al. 2017

Neuroscience & Biobehavioral Reviews

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Severe stress in early life, such as childhood abuse and neglect, constitutes a major risk factor in the etiology of psychiatric disorders and somatic diseases. Importantly, these long-term effects may impact the next generation. The intergenerational transmission of maternal early life stress (ELS) may occur via pre-and postnatal pathways, such as alterations in maternal-fetal-placental stress physiology, maternal depression during pregnancy and postpartum, as well as impaired mother-offspring interactions. The neuropeptide oxytocin (OT) has gained considerable attention for its role in modulating all of these assumed transmission pathways. Moreover, central and peripheral OT signaling pathways are highly sensitive to environmental exposures and may be compromised by ELS with implications for these putative transmission mechanisms. Together, these data suggest that OT pathways play an important role in the intergenerational transmission of maternal ELS in humans. By integrating recent studies on gene-environment interactions and epigenetic modifications in OT pathway genes, the present review aims to develop a conceptual framework of intergenerational transmission of maternal ELS that emphasizes the role of OT.

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Section: Gene-environment Interactions and Epigenetic Modificationmentioning

confidence: 94%

Oxytocin pathways in the intergenerational transmission of maternal early life stress

Toepfer

Heim

Entringer

et al. 2017

Neuroscience & Biobehavioral Reviews

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“…In humans, maternal touch and feed are considered also critical regulators of behavioral and stress responses in the offspring , although its importance as an obesity risk factor and the alteration of epigenetic processes have never been analyzed. However, it has been observed that childhood abuse, neglect and loss induce alterations of the epigenetic mechanisms (McGowan et al, 2009). They are major risk factor for developing depressive disorders later in life (Heim and Binder, 2012) and could be related with epigenetic mechanisms and chronic alterations in cortisol secretion in children that could affect body composition and be causative factors of early-onset obesity, metabolic syndrome, and type 2 diabetes (Pervanidou and Chrousos, 2011).…”

Section: Psychological Stressmentioning

confidence: 99%

Dietary factors, epigenetic modifications and obesity outcomes: Progresses and perspectives

Milagro

Mansego

Miguel

et al. 2013

Molecular Aspects of Medicine

252

161

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Nutritional factors play a life-long role in human health. Indeed, there is growing evidence that one of the mechanisms by which nutrients and bioactive compounds affect metabolic traits is epigenetics. Complex interactions among food components and histone modifications, DNA methylation, non-coding RNA expression and chromatin remodeling factors lead to a dynamic regulation of gene expression that controls the cellular phenotype. Although perinatal period is the time of highest phenotypic plasticity, contributing largely to developmental programming, also during adulthood there is evidence about a nutritional influence on epigenetic regulation. Similarly to type 2 diabetes, hypertension, atherosclerosis and other metabolic disorders, obesity predisposition and weight loss outcomes have been repeatedly associated to changes in epigenetic patterns. Different non-nutritional risk factors that usually accompany obesity seem also to be involved in these epigenetic modifications, especially hyperglycemia, inflammation, hypoxia and oxidative stress. There are currently three major objectives in epigenetic research in relation to obesity: to search for epigenetic biomarkers to predict future health problems or detect the individuals at most risk, to understand the obesity-related environmental factors that could modulate gene expression by affecting epigenetic mechanisms, and to study novel therapeutic strategies based on nutritional or pharmacological agents that can modify epigenetic marks. At this level, the major tasks are: development of robust epigenetic biomarkers of weight regulation, description of those epigenetic marks more susceptible to be modified by dietary exposures, identification of the active ingredients (and the doses) that alter the epigenome, assessment of the real importance of other obesity-related factors on epigenetic regulation, determination of the period of life in which best results are obtained, and understanding of the importance of the inheritance of these epigenetic marks.

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“…A set of recent studies [94] provides at least correlational evidence for the idea that comparable epigenetic modifications might occur in humans in response to variations in parent-offspring interactions. These studies examined the methylation status of the exon 1 F promoter of the GR gene, which corresponds to the exon 1 7 promoter in the rat [95], in hippocampal samples obtained from victims of suicide or controls (sudden, involuntary death).…”

Section: The Epigenetics Of Phenotypic Plasticitymentioning

confidence: 99%

Environmental regulation of the neural epigenome

et al. 2011

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a b s t r a c tParental effects are a major source of phenotypic plasticity. Moreover, there is evidence from studies with a wide range of species that the relevant parental signals are influenced by the quality of the parental environment. The link between the quality of the environment and the nature of the parental signal is consistent with the idea that parental effects, whether direct or indirect, might serve to influence the phenotype of the offspring in a manner that is consistent with the prevailing environmental demands. In this review we explore recent studies from the field of 'environmental epigenetics' that suggest that (1) DNA methylation states are far more variable than once thought and that, at least within specific regions of the genome, there is evidence for both demethylation and remethylation in post-mitotic cells and (2) that such remodeling of DNA methylation can occur in response to environmentally-driven, intracellular signaling pathways. Thus, studies of variation in mother-offspring interactions in rodents suggest that parental signals operate during pre-and/ or post-natal life to influence the DNA methylation state at specific regions of the genome leading to sustained changes in gene expression and function. We suggest that DNA methylation is a candidate mechanism for parental effects on phenotypic variation.

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Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse

Cited by 3,036 publications

References 50 publications

Oxytocin pathways in the intergenerational transmission of maternal early life stress

Oxytocin pathways in the intergenerational transmission of maternal early life stress

Dietary factors, epigenetic modifications and obesity outcomes: Progresses and perspectives

Environmental regulation of the neural epigenome

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