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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

DNA methylation at the CYP11A1 methylation locus in acute mania.A) DNA methylation between cases and controls B) DNA methylation with anti-psychotic, lithium, valproate, anti-convulsant other than lithium, atypical anti-pscyhotic use and controls C) DNA methylation at baseline and at six month follow up.
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pone.0132001.g001: DNA methylation at the CYP11A1 methylation locus in acute mania.A) DNA methylation between cases and controls B) DNA methylation with anti-psychotic, lithium, valproate, anti-convulsant other than lithium, atypical anti-pscyhotic use and controls C) DNA methylation at baseline and at six month follow up.

Mentions: We performed genome wide DNA methylation analysis in 20 individuals hospitalized with acute mania (case group I—see Table 1) and 20 unaffected controls. We found a single locus that differed between the individuals hospitalized with mania and controls (p<.006, Fig 1A). This pyrosequencing validated locus was a CpG site (chr15:74645873 genome build hg19) located near the cytochrome P450, family 11, subfamily A, polypeptide 1 (CYP11A1) gene,. The levels of methylation of this locus did not differ by covariates such as sex (p = 0.49 t = -0.705) and age (p = 0.48, t = 0.712) Within the group of individuals with mania we did not find an association between levels of methylation of this locus and class of medication received (Fig 1B).


Association of DNA Methylation with Acute Mania and Inflammatory Markers.

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

DNA methylation at the CYP11A1 methylation locus in acute mania.A) DNA methylation between cases and controls B) DNA methylation with anti-psychotic, lithium, valproate, anti-convulsant other than lithium, atypical anti-pscyhotic use and controls C) DNA methylation at baseline and at six month follow up.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0132001.g001: DNA methylation at the CYP11A1 methylation locus in acute mania.A) DNA methylation between cases and controls B) DNA methylation with anti-psychotic, lithium, valproate, anti-convulsant other than lithium, atypical anti-pscyhotic use and controls C) DNA methylation at baseline and at six month follow up.
Mentions: We performed genome wide DNA methylation analysis in 20 individuals hospitalized with acute mania (case group I—see Table 1) and 20 unaffected controls. We found a single locus that differed between the individuals hospitalized with mania and controls (p<.006, Fig 1A). This pyrosequencing validated locus was a CpG site (chr15:74645873 genome build hg19) located near the cytochrome P450, family 11, subfamily A, polypeptide 1 (CYP11A1) gene,. The levels of methylation of this locus did not differ by covariates such as sex (p = 0.49 t = -0.705) and age (p = 0.48, t = 0.712) Within the group of individuals with mania we did not find an association between levels of methylation of this locus and class of medication received (Fig 1B).

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