Dataset Information

BDNF Methylation and Suicidal Ideation in Patients with Acute Coronary Syndrome.

ABSTRACT: OBJECTIVE:Patients with acute coronary syndrome (ACS) are at an increased risk of suicide. It is well known that epigenetic mechanisms may explain the pathophysiology of suicidal behavior including suicidal ideation (SI), but no study has explored these mechanisms in ACS populations. METHODS:In total, 969 patients were initially recruited within 2 weeks of the acute coronary event and, 711 patients were successfully followed up 1 year after ACS. SI was evaluated using the relevant items on the Montgomery-Åsberg Depression Rating Scale and covariates potentially affecting SI were estimated. RESULTS:Brain-derived neurotrophic factor (BDNF) hypermethylation was associated with SI in both the acute and chronic phases of ACS, although the association was not statistically significant in the acute phase after applying Bonferroni's correction. CONCLUSION:These results suggested that BDNF hypermethylation may have played a role in an epigenetic predisposition for SI in ACS patients, particularly during the chronic phase.

SUBMITTER: Kang HJ

PROVIDER: S-EPMC6259000 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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BDNF Methylation and Suicidal Ideation in Patients with Acute Coronary Syndrome.

Kang Hee-Ju HJ Bae Kyung-Yeol KY Kim Sung-Wan SW Shin Il-Seon IS Hong Young Joon YJ Ahn Youngkeun Y Jeong Myung Ho MH Yoon Jin-Sang JS Kim Jae-Min JM

Psychiatry investigation 20181001 11

<h4>Objective</h4>Patients with acute coronary syndrome (ACS) are at an increased risk of suicide. It is well known that epigenetic mechanisms may explain the pathophysiology of suicidal behavior including suicidal ideation (SI), but no study has explored these mechanisms in ACS populations.<h4>Methods</h4>In total, 969 patients were initially recruited within 2 weeks of the acute coronary event and, 711 patients were successfully followed up 1 year after ACS. SI was evaluated using the relevant ...[more]

PMID: 30380818

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Project description:Stress plays an important role in major depressive disorder (MDD) and is one of the state dependent factors in suicidal behavior. A dysfunctional hypothalamic-pituitary-adrenal axis is a common feature in this disorder. The involvement of environmental factors has added additional complexity to understanding depression or suicidal behavior. In this regard, epigenetic regulation has been considered a mechanistic interface between environmental stress stimuli and altered functioning of underlying gene network that may increase susceptibility to depression or suicidal behavior. The present study examined whether epigenetic modifications of stress related genes are associated with MDD and whether there are differences in these epigenetic marks between depressed individuals with and without serious suicidal ideation. Using MeDIP analysis in genomic DNA isolated from peripheral blood mononuclear cells (PBMC) of healthy controls (n = 20), MDD patients with (n = 14) or without serious suicidal ideation (n = 10), we studied methylation of the stress-associated genes, Brain Derived Neurotrophic Factor (BDNF), Nuclear Receptor Subfamily 3 Group C Member 1 (NR3C1), FK506 Binding Protein 5 (FKBP5), Corticotropin Releasing Hormone Binding Protein (CRHBP), and Corticotropin Releasing Hormone Receptor 1 (CRHR1). In addition, we determined their transcript levels in RNAs isolated from the same PBMC. We found that BDNF, FKBP5, CRHBP, and NR3C1 gene promoters were significantly hypermethylated in MDD patients with and without suicidal ideation. We also found concomitant reductions in expression of BDNF, FKBP5 transcript variants (1, 2 and 3), and NR3C1 genes in these patients, suggesting that promoter hypermethylation in these genes may functionally be associated with their observed downregulation in MDD patients. In a secondary analysis, methylation of these genes was compared between MDD patients with or without serious suicidal ideation and controls. The MDD with serious suicidal ideation were significantly different from controls while the MDD without were not, although MDD with or without suicidal ideation were not different from each other, likely owning to a relatively small sample size. Thus, our findings underline the importance of epigenetic modifications of stress-associated genes in depression and, possibly, suicidal behavior, which, in future, needs to be confirmed in a larger patient population.

Dataset Information

BDNF Methylation and Suicidal Ideation in Patients with Acute Coronary Syndrome.

Publications

BDNF Methylation and Suicidal Ideation in Patients with Acute Coronary Syndrome.

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