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Association of DNA Methylation with Acute Mania and Inflammatory Markers.

Sabunciyan S, Maher B, Bahn S, Dickerson F, Yolken RH - PLoS ONE (2015)

Bottom Line: We identified a methylation locus in the CYP11A1 gene, which is regulated by corticotropin, that is hypo-methylated in individuals hospitalized for mania compared with unaffected controls.In addition, we found that methylation levels at the CYP11A1 locus were significantly correlated with three inflammatory markers in serum in acute mania cases but not in unaffected controls.We conclude that mania is associated with alterations in levels of DNA methylation and inflammatory markers.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Johns Hopkins University, Baltimore, MD, United States of America.

ABSTRACT
In order to determine whether epigenetic changes specific to the manic mood state can be detected in peripheral blood samples we assayed DNA methylation levels genome-wide in serum samples obtained from 20 patients hospitalized for mania and 20 unaffected controls using the Illumina 450K methylation arrays. We identified a methylation locus in the CYP11A1 gene, which is regulated by corticotropin, that is hypo-methylated in individuals hospitalized for mania compared with unaffected controls. DNA methylation levels at this locus appear to be state related as levels in follow-up samples collected from mania patients six months after hospitalization were similar to those observed in controls. In addition, we found that methylation levels at the CYP11A1 locus were significantly correlated with three inflammatory markers in serum in acute mania cases but not in unaffected controls. We conclude that mania is associated with alterations in levels of DNA methylation and inflammatory markers. Since epigenetic markers are potentially malleable, a better understanding of the role of epigenetics may lead to new methods for the prevention and treatment of mood disorders.

No MeSH data available.


Related in: MedlinePlus

The correlation between DNA methylation at the CYP11A1 locus and inflammatory markers.Percent DNA methylation is plotted on the Y-axis against A) Interleukin-1 receptor antagonist B) Angiopoietin-2 and C) C-Reactive Protein levels on the X-axis. A separate regression line is drawn for acute mania cases and controls.
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pone.0132001.g002: The correlation between DNA methylation at the CYP11A1 locus and inflammatory markers.Percent DNA methylation is plotted on the Y-axis against A) Interleukin-1 receptor antagonist B) Angiopoietin-2 and C) C-Reactive Protein levels on the X-axis. A separate regression line is drawn for acute mania cases and controls.

Mentions: We next examined whether inflammatory markers which have been reported to be extensively increased in mania were significantly associated with DNA methylation at the CYP11A1 locus. We also compared the effects of inflammation on DNA methylation marks between cases and controls. The regression analysis we performed revealed that the levels of Interleukin-1 receptor antagonist angiopoietin-2, and C reactive protein were significantly associated with DNA methylation in acute mania cases but not controls (p = 2.42e-05 padj = 0.004 f = 15.74; p = 7.90e-05 padj = 0.013 f = 14.17; p = 9.15e-05 padj = 0.0145 f = 11.45, respectively), (Fig 2) after correcting for multiple testing. All of the associations between inflammatory markers and DNA methylation in the unaffected controls failed to surpass the threshold for statistical significance.


Association of DNA Methylation with Acute Mania and Inflammatory Markers.

Sabunciyan S, Maher B, Bahn S, Dickerson F, Yolken RH - PLoS ONE (2015)

The correlation between DNA methylation at the CYP11A1 locus and inflammatory markers.Percent DNA methylation is plotted on the Y-axis against A) Interleukin-1 receptor antagonist B) Angiopoietin-2 and C) C-Reactive Protein levels on the X-axis. A separate regression line is drawn for acute mania cases and controls.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492496&req=5

pone.0132001.g002: The correlation between DNA methylation at the CYP11A1 locus and inflammatory markers.Percent DNA methylation is plotted on the Y-axis against A) Interleukin-1 receptor antagonist B) Angiopoietin-2 and C) C-Reactive Protein levels on the X-axis. A separate regression line is drawn for acute mania cases and controls.
Mentions: We next examined whether inflammatory markers which have been reported to be extensively increased in mania were significantly associated with DNA methylation at the CYP11A1 locus. We also compared the effects of inflammation on DNA methylation marks between cases and controls. The regression analysis we performed revealed that the levels of Interleukin-1 receptor antagonist angiopoietin-2, and C reactive protein were significantly associated with DNA methylation in acute mania cases but not controls (p = 2.42e-05 padj = 0.004 f = 15.74; p = 7.90e-05 padj = 0.013 f = 14.17; p = 9.15e-05 padj = 0.0145 f = 11.45, respectively), (Fig 2) after correcting for multiple testing. All of the associations between inflammatory markers and DNA methylation in the unaffected controls failed to surpass the threshold for statistical significance.

Bottom Line: We identified a methylation locus in the CYP11A1 gene, which is regulated by corticotropin, that is hypo-methylated in individuals hospitalized for mania compared with unaffected controls.In addition, we found that methylation levels at the CYP11A1 locus were significantly correlated with three inflammatory markers in serum in acute mania cases but not in unaffected controls.We conclude that mania is associated with alterations in levels of DNA methylation and inflammatory markers.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Johns Hopkins University, Baltimore, MD, United States of America.

ABSTRACT
In order to determine whether epigenetic changes specific to the manic mood state can be detected in peripheral blood samples we assayed DNA methylation levels genome-wide in serum samples obtained from 20 patients hospitalized for mania and 20 unaffected controls using the Illumina 450K methylation arrays. We identified a methylation locus in the CYP11A1 gene, which is regulated by corticotropin, that is hypo-methylated in individuals hospitalized for mania compared with unaffected controls. DNA methylation levels at this locus appear to be state related as levels in follow-up samples collected from mania patients six months after hospitalization were similar to those observed in controls. In addition, we found that methylation levels at the CYP11A1 locus were significantly correlated with three inflammatory markers in serum in acute mania cases but not in unaffected controls. We conclude that mania is associated with alterations in levels of DNA methylation and inflammatory markers. Since epigenetic markers are potentially malleable, a better understanding of the role of epigenetics may lead to new methods for the prevention and treatment of mood disorders.

No MeSH data available.


Related in: MedlinePlus