DNA Methylation Analysis of the NR3C1 Gene in Patients with Schizophrenia

Liu, Linlin; Wu, Jian; Qing, Lili; Li, Jiajue; Yang, Hao; Ji, Aicen; Yan, Ming; Hu, Liping; Nie, Shengjie

doi:10.1007/s12031-020-01525-8

Cited by 24 publications

(17 citation statements)

References 43 publications

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“…Our previous studies on the methylation of the NR3C1 and NR3C2 genes in the HPA axis and SCZ patients have produced very significant results. The methylation status of the NR3C1 and NR3C2 genes is significantly associated with SCZ and is sex dependent to some extent (Liu et al 2020a and2020b;Qing et al 2020;Qing et al 2021). Based on the results of this study, we strongly believe that HPA axis methylation can mediate environmental and genetic interactions and affect the pathogenesis of SCZ.…”

Section: Discussionmentioning

confidence: 60%

“…The hypothalamic-pituitary-adrenal (HPA) axis is an important stress response system that maintains homeostasis through the responses to environmental stressors (Russo et al 2012). Our previous studies have shown that DNA methylation of the NR3C1 and NR3C2 genes in the HPA axis leads to a risk of mental illness, including SCZ and aggressive behavior (Liu et al 2020a and2020b;Qing et al 2020;Qing et al 2021). As the central driving force in the HPA axis (Zhou and Fang, 2018), the CRH gene has attracted our attention.…”

Section: Introductionmentioning

confidence: 99%

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Sex-Dependent Association of DNA Methylation in the Coding Region of the Corticotropin-Releasing Hormone Gene and Schizophrenia

Qing

Xiong

et al. 2021

Preprint

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Schizophrenia (SCZ) is a common mental disease causing severe chronic disability. Epigenetic changes in HPA axis-related genes are considered to play an important role in SCZ pathogenesis. Unfortunately, the methylation status of the corticotropin-releasing hormone ( CRH ) gene, which is the central driving force in the HPA axis, has not been reported in SCZ patients. Here, we used the sodium bisulfite and MethylTarget methods to detect the DNA methylation status of the CRH gene coding region in peripheral blood samples from 70 schizophrenic patients and 68 healthy controls. The results showed that the methylation level of the CRH gene CDS was significantly increased in SCZ patients, especially in the male subgroup. In conclusion, this study showed that differences in CRH gene CDS methylation were detectable in the peripheral blood of SCZ patients and that epigenetic abnormalities in the CRH gene were closely related to SCZ, revealing that epigenetic processes may mediate the pathophysiology of SCZ. Further research should address the underlying mechanism whereby CRH gene methylation regulates the occurrence and development of SCZ.

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Section: Discussionmentioning

confidence: 60%

Section: Introductionmentioning

confidence: 99%

Sex-Dependent Association of DNA Methylation in the Coding Region of the Corticotropin-Releasing Hormone Gene and Schizophrenia

Qing

Xiong

et al. 2021

Preprint

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“…We know of only two studies that measured DNA methylation of NR3C1 in SZ. One Chinese study reported no significant difference for the average value of CpG sites covering region 1 F between patients with SZ and controls [ 12 ]. However, patients had significantly higher DNA methylation at CpG21 than controls.…”

Section: Discussionmentioning

confidence: 99%

“…Studies on DNA methylation of DRD2 have reported mixed results, including no significant difference [ 8 ] or lower methylation rates [ 9 – 11 ] compared to healthy controls. For NR3C1, results have varied depending on which CpG sites or components were analyzed, e.g., hypomethylation at 1D-CpG8 and hypermethylation at 1B-CpG15 and 1F-CpG21 [ 12 ] and hypomethylation or hypermethylation at component 2, including 5 CpG sites, depending on the stage of psychosis [ 13 ]. Previous studies have been limited because subjects were mainly chronic SZ patients and clinical correlates were not investigated adequately.…”

Section: Introductionmentioning

confidence: 99%

DNA Methylation Profiles of the DRD2 and NR3C1 Genes in Patients with Recent-Onset Psychosis

Piao

Cui

et al. 2022

Disease Markers

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Objectives. Dopamine receptor D2 gene (DRD2) and glucocorticoid receptor gene (NR3C1) are implicated in the development of psychosis. We investigated methylation levels of DRD2 and NR3C1 in peripheral blood of patients with recent-onset (RO) psychosis using bisulfite pyrosequencing as well as its association with childhood trauma and rumination. Methods. In all, 51 individuals with RO psychosis and 47 healthy controls were recruited. DNA methylation levels in the targeted regions of two genes were analyzed and compared. Childhood trauma and rumination were evaluated using the Early Trauma Inventory Self-Report Short Form (ETI-SF) and Brooding Scale (BS), respectively. Correlations between the scores of the ETI-SF and BS and methylation levels were explored. Results. For DRD2, we found no significant differences between groups in terms of methylation level or association with childhood trauma or rumination. For NR3C1, we found a trend level significance for average value of all CpG sites and significant hypermethylation or hypomethylation at specific sites. There was also a significant positive correlation between the methylation level at the CpG8 site of NR3C1 exon 1F and negative symptom subscale score of the PANSS (PANSS-N). Conclusion. Epigenetic alterations of NR3C1 are associated with the pathophysiology of psychosis. Further epigenetic studies will elucidate the molecular mechanisms underpinning the pathophysiology of psychosis.

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“…org/mpg/ricopili/; accessed at 22 February 2021). However, NR3C1 methylation in blood samples was reported to be associated with schizophrenia, in females, supporting its role in the pathophysiology of schizophrenia [21]. As for FKBP5 itself, recent GWAS do not find an association with schizophrenia, nor with major depressive or bipolar disorders (https://data.broadinstitute.org/mpg/ricopili/; accessed at 22 February 2021).…”

Section: Introductionmentioning

confidence: 99%

Gene Expression Meta-Analysis of Cerebellum Samples Supports the FKBP5 Gene-Environment Interaction Model for Schizophrenia

Hertzberg

Zohar

Yitzhaky

2021

Life

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Background: One of the most studied molecular models of gene-environment interactions is that of FKBP5, which has been shown to interact with childhood adversity to increase the risk of psychiatric disorders, and has been implicated in schizophrenia. While the model predicts up-regulation of FKBP5, previous brain samples gene expression studies yielded inconsistent results. Methods: We performed a systematic gene expression meta-analysis of FKBP5 and NR3C1, a glucocorticoid receptor inhibited by FKBP5, in cerebellum samples of patients with schizophrenia. The gene expression databases GEO, SMRI and those of NIMH were searched, and out of six screened datasets, three were eligible for the meta-analysis (overall 69 with schizophrenia and 78 controls). Results: We detected up-regulation of FKBP5 and down-regulation of NR3C1 in schizophrenia, and a negative correlation between their expression patterns. Correlation analysis suggested that the detected differential expression did not result from potential confounding factors. Conclusions: Our results give significant support to the FKBP5 gene-environment interaction model for schizophrenia, which provides a molecular mechanism by which childhood adversity is involved in the development of the disorder. To explore FKBP5’s potential as a therapeutic target, a mapping of its differential expression patterns in different brain regions of schizophrenia patients is needed.

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DNA Methylation Analysis of the NR3C1 Gene in Patients with Schizophrenia

Cited by 24 publications

References 43 publications

Sex-Dependent Association of DNA Methylation in the Coding Region of the Corticotropin-Releasing Hormone Gene and Schizophrenia

Sex-Dependent Association of DNA Methylation in the Coding Region of the Corticotropin-Releasing Hormone Gene and Schizophrenia

DNA Methylation Profiles of the DRD2 and NR3C1 Genes in Patients with Recent-Onset Psychosis

Gene Expression Meta-Analysis of Cerebellum Samples Supports the FKBP5 Gene-Environment Interaction Model for Schizophrenia

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DNA Methylation Analysis of the NR3C1 Gene in Patients with Schizophrenia

Cited by 24 publications

References 43 publications

Sex-Dependent Association of DNA&nbsp;Methylation in&nbsp;the Coding Region&nbsp;of the Corticotropin-Releasing Hormone&nbsp;Gene and Schizophrenia

Sex-Dependent Association of DNA&nbsp;Methylation in&nbsp;the Coding Region&nbsp;of the Corticotropin-Releasing Hormone&nbsp;Gene and Schizophrenia

DNA Methylation Profiles of the DRD2 and NR3C1 Genes in Patients with Recent-Onset Psychosis

Gene Expression Meta-Analysis of Cerebellum Samples Supports the FKBP5 Gene-Environment Interaction Model for Schizophrenia

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Sex-Dependent Association of DNA Methylation in the Coding Region of the Corticotropin-Releasing Hormone Gene and Schizophrenia

Sex-Dependent Association of DNA Methylation in the Coding Region of the Corticotropin-Releasing Hormone Gene and Schizophrenia