Glucocorticoid receptor gene (NR3C1) promoter is hypermethylated in Thai females with major depressive disorder

Nantharat, Matchima; Wanitchanon, T; Amesbutr, M; Tammachote, Rachaneekorn; Praphanphoj, Verayuth

doi:10.4238/2015.december.29.15

Cited by 40 publications

(21 citation statements)

References 22 publications

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“…A positive relationship between LINE-1 methylation and age is well established and has also been reported in psychiatric disorders 34. However, unchanged LINE-1 methylation from this study is in agreement with a previous finding in blood samples in MDD 35. The lack of any indication of a change in global DNA methylation indicates that the findings in PVALB are independent of such an effect and perhaps specific for that gene.…”

Section: Discussionsupporting

confidence: 92%

Parvalbumin Promoter Methylation Altered in Major Depressive Disorder

et al. 2019

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Aims: To determine the extent of DNA methylation of parvalbumin gene (PVALB) promoter in major depressive disorder (MDD) patients with and without suicide attempt in comparison with healthy controls.Methods: The extracted DNA from dried blood spots of MDD patients (n = 92) including non-suicidal MDD and suicidal-MDD subgroups (n = 45 and n = 47, respectively) and age-matched control subjects (n = 95) was used for DNA methylation analysis at four CpG sites in the promoter sequence of PVALB by pyrosequencing.Results: The PVALB methylation was significantly increased at CpG2 and decreased at CpG4 in the MDD group compared to the control group, while there was no difference between non-suicidal MDD and suicidal-MDD subgroups. A significant inverse correlation of severity of MDD was indicated only for CpG4.Conclusion: This study provides the first evidence of abnormalities of PVALB promoter methylation in MDD and its correlation with MDD severity indicating a role for epigenetics in this psychiatric disorder.

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Section: Discussionsupporting

confidence: 92%

Parvalbumin Promoter Methylation Altered in Major Depressive Disorder

et al. 2019

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“…Despite finding significantly lower DNA methylation in the downstream region of NR3C1 CpG sites associated with MDD, we did not observe significant gene expression differences associated with MDD status; however, MDD does not significantly influence DNA methylation at the EGR1 -associated CpG sites, suggesting that its functional consequences (as measured by NR3C1 expression) may be limited compared to the effects of childhood maltreatment exposure. This null gene expression finding associated with MDD is consistent with a previous study examining DNA methylation and gene expression in a group of MDD patients and healthy controls (Nantharat et al, 2015). …”

Section: Discussionsupporting

confidence: 92%

“…Similarly, our MDD results are also consistent with a recent study examining NR3C1 DNA methylation levels which reported decreased DNA methylation (Na et al, 2014). It should be noted that one other study that examined NR3C1 promoter region DNA methylation levels reported a significant increase at their CpG site 7 (corresponding to CpG site 5 in this study) in MDD cases compared to healthy controls (Nantharat et al, 2015). Additionally, only one of their CpG sites overlaps with the region we found to be significantly associated with MDD in our study, which is a point of consideration when comparing results.…”

Section: Discussionmentioning

confidence: 47%

“…A recent study examined NR3C1 DNA methylation and hippocampal volume in a group of participants with MDD compared to healthy controls, finding MDD patients had significantly lower levels of DNA methylation within the promoter region of NR3C1 (Na et al, 2014). Additionally, a second paper examined NR3C1 DNA methylation in a group of participants with and without MDD, reporting a significant increase in NR3C1 DNA methylation at a single CpG site associated with the disorder (Nantharat et al, 2015). These studies report opposite associations between MDD and NR3C1 DNA methylation levels measured in blood; however, the relationship among childhood maltreatment, MDD, and NR3C1 DNA methylation was not addressed in either work.…”

Section: Introductionmentioning

confidence: 99%

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Glucocorticoid receptor DNA methylation, childhood maltreatment and major depression

Bustamante

Aiello

Galea

et al. 2016

Journal of Affective Disorders

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Introduction Altered DNA methylation (DNAm) levels of hypothalamic-pituitary-adrenal (HPA) axis genes has been associated with exposure to childhood maltreatment (CM) and depression; however, it is unknown whether CM and depression have joint and potentially interacting effects on the glucocorticoid receptor (NR3C1) DNAm. We investigated the impact of CM and lifetime major depressive disorder (MDD) on NR3C1 DNAm and gene expression (GE) in 147 adult participants from the Detroit Neighborhood Health Study. Methods NR3C1 promoter region DNAm was assessed via pyrosequencing using whole blood-derived DNA. Quantitative RT-PCR assays measured GE from leukocyte-derived RNA. Linear regression models were used to examine the relationship among CM, MDD, and DNAm. Results Both CM and MDD were significant predictors of NR3C1 DNAm: CM was associated with an increase in DNAm in an EGR1 transcription factor binding site (TFBS), whereas MDD was associated with a decrease in DNAm downstream of the TFBS. No significant CM-MDD interactions were observed. CM alone was associated with significantly lower NR3C1 GE. Limitations Our report of CM is a retrospective self-report of abuse, which may introduce recall bias. DNAm was measured in whole blood and may not reflect brain-derived DNAm levels. Conclusions CM and MDD are both associated with altered DNAm levels in the NR3C1 promoter region, however the location and direction of effects differ between the two exposures, and the functional effects, as measured by GE, appear to be limited to CM exposure alone. CM exposure may be biologically embedded in this key HPA axis gene.

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“…This observation agrees with the association of glucocorticoid receptor with depressive disorders. Thus, high levels of Nr3c1 promoter methylation have been associated with major depressive disorder (Nantharat et al, 2015). As DNA methylation usually represses gene transcription, our results support the hypothesis that decreased Nr3c1 receptor level could be an indicative factor for depressive-like behavior.…”

Section: Discussionsupporting

confidence: 84%

Influence of behavioral traits in the inter-individual variability of nociceptive, emotional and cognitive manifestations of neuropathic pain

et al. 2019

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Neuropathic pain is a complex disorder associated with emotional and cognitive deficits that may impair nociceptive manifestations. There is high inter-individual variability in the manifestations of human neuropathic pain, which largely depends on personality traits. We aim to identify the influence of different behavioral traits in the interindividual vulnerability to neuropathic pain manifestations using behavioral, electrophysiological and genetic approaches. We first selected mice with extreme social and emotional traits and look for correlation with the spontaneous neuronal activity in the central amygdala. Neuropathic pain was induced to these mice to evaluate the influence of behavioral traits on nociceptive manifestations and gene expression profiles in the amygdala. Our results show an association of the spontaneous central amygdala neuronal activity with the sociability behavior. We demonstrate that low sociable, high anxious and low depressive phenotypes develop enhanced nociceptive hypersensitivity after nerve injury. However, greater emotional alterations and cognitive impairment are observed in high sociable, anxious-like and depressive-like mice, indicating that nociceptive, emotional and cognitive manifestations of neuropathic pain do not correlate with each other. Gene analyses identify high Pdyn and Il6 levels in the amygdala as indicative of enhanced nociceptive hypersensitivity and reveal an association between high Gadd45 expression and attenuated emotional and cognitive manifestations of neuropathic pain.

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Glucocorticoid receptor gene (NR3C1) promoter is hypermethylated in Thai females with major depressive disorder

Cited by 40 publications

References 22 publications

Parvalbumin Promoter Methylation Altered in Major Depressive Disorder

Parvalbumin Promoter Methylation Altered in Major Depressive Disorder

Glucocorticoid receptor DNA methylation, childhood maltreatment and major depression

Influence of behavioral traits in the inter-individual variability of nociceptive, emotional and cognitive manifestations of neuropathic pain

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