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Epigenetic Changes in the CRH Gene are Related to Severity of Suicide Attempt and a General Psychiatric Risk Score in Adolescents
Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, Stockholm, Sweden; Umeå Univ, Dept Clin Sci Psychiat, Umeå, Sweden.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology. Umeå Univ, Dept Clin Sci Psychiat, Umeå, Sweden.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
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2018 (English)In: EBioMedicine, ISSN 0360-0637, E-ISSN 2352-3964, Vol. 27, p. 123-133, article id S2352-3964(17)30499-1Article in journal (Refereed) Published
Abstract [en]

The aim of this study, comprising 88 suicide attempters, was to identify hypothalamic-pituitary-adrenal (HPA) -axis coupled CpG-sites showing methylation shifts linked to severity of the suicide attempt. Candidate methylation loci were further investigated as risk loci for a general psychiatric risk score in two cohorts of adolescents (cohort 1 and 2). The genome-wide methylation pattern was measured in whole blood using the Illumina Infinium Methylation EPIC BeadChip. Subjects were stratified into high-risk and low-risk groups based on the severity of the suicidal behavior. We included CpG sites located within 2000 basepairs away from transcriptional start site of the following HPA-axis coupled genes: corticotropin releasing hormone (CRH), corticotropin releasing hormone binding protein (CRHBP), corticotropin releasing hormone receptor 1 (CRHR1), corticotropin releasing hormone receptor 2 (CRHR2), FK506-binding protein 51 (FKBP5) and the glucocorticoid receptor (NR3C1). The methylation state of two corticotropin releasing hormone (CRH)-associated CpG sites were significantly hypomethylated in the high-risk group of suicide attempters (n = 31) (cg19035496 and cg23409074) (p < 0.001). Adolescent cohort 1 and 2 consisted of 129 and 93 subjects, respectively, and were stratified by the in silico generated DAWBA measurements of a general psychiatric risk score into high-risk group (>~50% risk) or controls. In adolescent cohort 2, cg19035496 was hypermethylated in subjects with a high general psychiatric risk score. Our results show epigenetic changes in the CRH gene related to severity of suicide attempt in adults and a general psychiatric risk score in adolescents.

Place, publisher, year, edition, pages
2018. Vol. 27, p. 123-133, article id S2352-3964(17)30499-1
Keywords [en]
Adolescent depression, CRH gene, Epigenetics, HPA axis, Methylation, Suicide, Suicide attempt
National Category
Psychiatry
Identifiers
URN: urn:nbn:se:uu:diva-342179DOI: 10.1016/j.ebiom.2017.12.018ISI: 000425875400017PubMedID: 29277323OAI: oai:DiVA.org:uu-342179DiVA, id: diva2:1183822
Funder
Swedish Research Council, 5454; K2009-61P21304-04-4; K2009-61X-21305-01-1The Swedish Brain FoundationStockholm County Council, SLL-20150269Västerbotten County Council, VLL-582221Available from: 2018-02-19 Created: 2018-02-19 Last updated: 2018-04-17Bibliographically approved

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