Epigenetic Changes in the CRH Gene are Related to Severity of Suicide Attempt and a General Psychiatric Risk Score in Adolescents

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...

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Main Authors: Jussi Jokinen, Adrian E. Boström, Ali Dadfar, Diana M. Ciuculete, Andreas Chatzittofis, Marie Åsberg, Helgi B. Schiöth
Format: Article
Language:English
Published: Elsevier 2018-01-01
Series:EBioMedicine
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2352396417304991
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spelling doaj-ae46d4cbad3b4744b2783cf9e821e88a2020-11-25T01:33:19ZengElsevierEBioMedicine2352-39642018-01-0127C12313310.1016/j.ebiom.2017.12.018Epigenetic Changes in the CRH Gene are Related to Severity of Suicide Attempt and a General Psychiatric Risk Score in AdolescentsJussi Jokinen0Adrian E. Boström1Ali Dadfar2Diana M. Ciuculete3Andreas Chatzittofis4Marie Åsberg5Helgi B. Schiöth6Department of Clinical Neuroscience/Center for Psychiatric Research, Karolinska Institutet, Stockholm, SwedenDepartment of Neuroscience/Functional Pharmacology, Uppsala University, Uppsala, SwedenDepartment of Clinical Sciences/Psychiatry, Umeå University, Umeå, SwedenDepartment of Neuroscience/Functional Pharmacology, Uppsala University, Uppsala, SwedenDepartment of Clinical Neuroscience/Center for Psychiatric Research, Karolinska Institutet, Stockholm, SwedenDepartment of Clinical Sciences, Karolinska Institutet, Stockholm, SwedenDepartment of Neuroscience/Functional Pharmacology, Uppsala University, Uppsala, SwedenThe 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.http://www.sciencedirect.com/science/article/pii/S2352396417304991SuicideSuicide attemptHPA axisCRH geneEpigeneticsMethylationAdolescent depression
collection DOAJ
language English
format Article
sources DOAJ
author Jussi Jokinen
Adrian E. Boström
Ali Dadfar
Diana M. Ciuculete
Andreas Chatzittofis
Marie Åsberg
Helgi B. Schiöth
spellingShingle Jussi Jokinen
Adrian E. Boström
Ali Dadfar
Diana M. Ciuculete
Andreas Chatzittofis
Marie Åsberg
Helgi B. Schiöth
Epigenetic Changes in the CRH Gene are Related to Severity of Suicide Attempt and a General Psychiatric Risk Score in Adolescents
EBioMedicine
Suicide
Suicide attempt
HPA axis
CRH gene
Epigenetics
Methylation
Adolescent depression
author_facet Jussi Jokinen
Adrian E. Boström
Ali Dadfar
Diana M. Ciuculete
Andreas Chatzittofis
Marie Åsberg
Helgi B. Schiöth
author_sort Jussi Jokinen
title Epigenetic Changes in the CRH Gene are Related to Severity of Suicide Attempt and a General Psychiatric Risk Score in Adolescents
title_short Epigenetic Changes in the CRH Gene are Related to Severity of Suicide Attempt and a General Psychiatric Risk Score in Adolescents
title_full Epigenetic Changes in the CRH Gene are Related to Severity of Suicide Attempt and a General Psychiatric Risk Score in Adolescents
title_fullStr Epigenetic Changes in the CRH Gene are Related to Severity of Suicide Attempt and a General Psychiatric Risk Score in Adolescents
title_full_unstemmed Epigenetic Changes in the CRH Gene are Related to Severity of Suicide Attempt and a General Psychiatric Risk Score in Adolescents
title_sort epigenetic changes in the crh gene are related to severity of suicide attempt and a general psychiatric risk score in adolescents
publisher Elsevier
series EBioMedicine
issn 2352-3964
publishDate 2018-01-01
description 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.
topic Suicide
Suicide attempt
HPA axis
CRH gene
Epigenetics
Methylation
Adolescent depression
url http://www.sciencedirect.com/science/article/pii/S2352396417304991
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