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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
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Department of Clinical Neuroscience/Center for Psychiatric Research, Karolinska Institutet, Stockholm, Sweden.
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2018 (English)In: EBioMedicine, ISSN 0360-0637, E-ISSN 2352-3964, Vol. 27, p. 123-133Article 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). Themethylation state of two corticotropin releasing hormone (CRH)-associated CpG siteswere 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 (>similar to 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
ELSEVIER SCIENCE BV , 2018. Vol. 27, p. 123-133
Keywords [en]
Suicide, Suicide attempt, HPA axis, CRH gene, Epigenetics, Methylation, Adolescent depression
National Category
Psychiatry
Identifiers
URN: urn:nbn:se:umu:diva-145805DOI: 10.1016/j.ebiom.2017.12.018ISI: 000425875400017PubMedID: 29277323OAI: oai:DiVA.org:umu-145805DiVA, id: diva2:1192397
Available from: 2018-03-22 Created: 2018-03-22 Last updated: 2018-08-08Bibliographically approved

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Jokinen, Jussi

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