Increased methylation at an unexplored glucocorticoid responsive element within exon 1D of NR3C1 gene is related to anxious-depressive disorders and decreased hippocampal connectivity

Palma-Gudiel, Helena; Córdova‐Palomera, Aldo; Tornador, Cristian; Falcón, Carles; Bargalló, Núria; Deco, Gustavo; Fañanás, Lourdes

doi:10.1016/j.euroneuro.2018.03.015

Cited by 44 publications

(22 citation statements)

References 38 publications

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“…Moreover, compared with suicides without childhood abuse, the exon 1B and 1C, but not 1H GR promoters were also hypermethylated while the expression of the variants 1B and 1C were decreased in the hippocampus of suicides with ELS exposure (Labonte et al, 2012). Additionally, in a study of monozygotic twin pairs, Palma-Gudiel et al (2018) demonstrated that increased exon 1D NR3C1 CpG-specific methylation was related to depressive symptoms and decreased hippocampal connectivity. Moreover, another monozygotic twin study revealed that DNAm at the NR3C1 mediated the association between childhood trauma and depression (Peng et al, 2018).…”

Section: Epigenetic Studies Focused On Human Beingsmentioning

confidence: 94%

“…It was reported that depressive patients harbored different profiles of the HPA axis, which might be due to a feature of the NR3C1 DNAm (Malhi and Mann, 2018). Furthermore, demographic characteristics (i.e., age and gender), types and severity of ELS (physical abuse, sexual abuse, emotional abuse, physical and emotional neglects), tissue specificity (i.e., subregions of the brain, blood), dynamic changes in epigenetic profiles (interacting with continuous environment actions), and study design contributed to this discrepancy (McGowan et al, 2009;Perroud et al, 2011;Kember et al, 2012;Bustamante et al, 2016;Cecil et al, 2016;Tyrka et al, 2016;Alexander et al, 2018;Palma-Gudiel et al, 2018;Peng et al, 2018;Fiacco et al, 2019). Besides, because research focusing on the figure of histone modification and noncoding RNA within NR3C1 is lacking, it is unknown whether DNAm, histone modification, and non-coding RNA coordinate or disintegrate with each other.…”

Section: Epigenetic Studies Focused On Human Beingsmentioning

confidence: 99%

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Effect of Early Life Stress on the Epigenetic Profiles in Depression

Xie

et al. 2020

Front. Cell Dev. Biol.

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Depression is one of the most common mental disorders and has caused an overwhelming burden on world health. Abundant studies have suggested that early life stress may grant depressive-like phenotypes in adults. Childhood adversities that occurred in the developmental period amplified stress events in adulthood. Epigenetic-environment interaction helps to explain the role of early life stress on adulthood depression. Early life stress shaped the epigenetic profiles of the HPA axis, monoamine, and neuropeptides. In the context of early adversities increasing the risk of depression, early life stress decreased the activity of the glucocorticoid receptors, halted the circulation and production of serotonin, and reduced the molecules involved in modulating the neurogenesis and neuroplasticity. Generally, DNA methylation, histone modifications, and the regulation of non-coding RNAs programmed the epigenetic profiles to react to early life stress. However, genetic precondition, subtypes of early life stress, the timing of epigenetic status evaluated, demographic characteristics in humans, and strain traits in animals favored epigenetic outcomes. More research is needed to investigate the direct evidence for how early life stress-induced epigenetic changes contribute to the vulnerability of depression.

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Section: Epigenetic Studies Focused On Human Beingsmentioning

confidence: 94%

Section: Epigenetic Studies Focused On Human Beingsmentioning

confidence: 99%

Effect of Early Life Stress on the Epigenetic Profiles in Depression

Xie

et al. 2020

Front. Cell Dev. Biol.

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“…The NR3C1 , encoding GR, is known as a major component of HPA axis against stress, and have been reported to be one of stress biomarkers with responses to psychosocial stress following the Trier Social Stress Test (TSST) [ 13 ]. The polymorphisms, methylation and expression of the NR3C1 gene have been indicated to be associated with depression and especially related to stress [ 14 , 15 , 16 , 17 , 18 , 19 ]. The CRF gene, that codes corticotropin-releasing factor, contributes to stress-related depressiveness [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

Cannabinoid CB2 Receptor Gene and Environmental Interaction in the Development of Psychiatric Disorders

et al. 2018

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CB2 cannabinoid receptor (CB2R) gene is associated with depression. We investigated the gene-environment interaction between CB2R function and diverse stressors. First, anxiety-like behavior during chronic-mild-stress (CMS) was evaluated in C57BL/6JJmsSlc mice following treatment with CB2R agonist JWH015 or inverse-agonist AM630. Second, locomotor activity and anxiety-like behavior were measured following exposure to an immune poly I:C stressor. Gene expressions of HPA axis related molecules, Fkbp5, Nr3c1 and Crf and pro-inflammatory cytokine Il-1b, as well as Bdnf as a key neurotrophin that supports neuron health, function, and synaptic plasticity, were determined in hippocampus of Cnr2 knockout mice, as indicators of stressful environment. CMS-induced anxiety-like behavior was enhanced by AM630 and reduced by JWH015 and fluvoxamine. Poly I:C reduced locomotor activity and increased anxiety-like behavior, and these effects were pronounced in the heterozygote than in the wild type mice. Fkbp5 and Nr3c1 expression were lower in the Cnr2 heterozygotes than in the wild type mice with Poly I:C treatment. These findings indicate that interaction between CB2R gene and stressors increases the risk of depression-like behaviors that may be linked with neuro-immune crosstalk. Further studies in human subjects are necessary to determine the role of CB2R and environmental interaction in the development of depression.

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“…However, both co-twins in this pair have almost identical methylation levels at these sites suggesting that their particular genomic DNA sequences may contain low-frequency SNVs associated with hyper-methylation such as SNP-containing probes [ 24 , 25 ]. Alternatively, the shared methylation profile could have arised in response to an environmental exposure common to both co-twins of the pair [ 29 ]. Thus, the relatively high methylation levels at these probes are not actually indicating stochastic epigenetic effects in healthy pairs.…”

Section: Discussionmentioning

confidence: 99%

Epigenetic outlier profiles in depression: A genome-wide DNA methylation analysis of monozygotic twins

et al. 2018

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Recent discoveries highlight the importance of stochastic epigenetic changes, as indexed by epigenetic outlier DNA methylation signatures, as a valuable tool to understand aberrant cell function and subsequent human pathology. There is evidence of such changes in different complex disorders as diverse as cancer, obesity and, to a lesser extent, depression. The current study was aimed at identifying outlying DNA methylation signatures of depressive psychopathology. Here, genome-wide DNA methylation levels were measured (by means of Illumina Infinium HumanMethylation450 Beadchip) in peripheral blood of thirty-four monozygotic twins informative for depressive psychopathology (lifetime DSM-IV diagnoses). This dataset was explored to identify outlying epigenetic signatures of depression, operationalized as extreme hyper- or hypo-methylation in affected co-twins from discordant pairs that is not observed across the rest of the study sample. After adjusting for blood cell count, there were thirteen CpG sites across which depressed co-twins from the discordant pairs exhibited outlying DNA methylation signatures. None of them exhibited a methylation outlier profile in the concordant and healthy pairs, and some of these loci spanned genes previously associated with neuropsychiatric phenotypes, such as GHSR and KCNQ1. This exploratory study provides preliminary proof-of-concept validation that epigenetic outlier profiles derived from genome-wide DNA methylation data may be related to depression risk.

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Increased methylation at an unexplored glucocorticoid responsive element within exon 1D of NR3C1 gene is related to anxious-depressive disorders and decreased hippocampal connectivity

Cited by 44 publications

References 38 publications

Effect of Early Life Stress on the Epigenetic Profiles in Depression

Effect of Early Life Stress on the Epigenetic Profiles in Depression

Cannabinoid CB2 Receptor Gene and Environmental Interaction in the Development of Psychiatric Disorders

Epigenetic outlier profiles in depression: A genome-wide DNA methylation analysis of monozygotic twins

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