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Methylation of HPA axis related genes in men with hypersexual disorder
Karolinska Inst, Dept Clin Neurosci Psychiat, Stockholm, Sweden.;Umea Univ, Dept Clin Sci Psychiat, Umea, Sweden..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
Karolinska Inst, Dept Clin Neurosci Psychiat, Stockholm, Sweden.;Univ Cyprus, Sch Med, Nicosia, Cyprus..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
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2017 (English)In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 80, 67-73 p.Article in journal (Refereed) Published
Abstract [en]

Hypersexual Disorder (HD) defined as non-paraphilic sexual desire disorder with components of compulsivity, impulsivity and behavioral addiction, and proposed as a diagnosis in the DSM 5, shares some overlapping features with substance use disorder including common neurotransmitter systems and dysregulated hypothalamic-pituitary-adrenal (HPA) axis function. In this study, comprising 67 HD male patients and 39 male healthy volunteers, we aimed to identify HPA-axis coupled CpG-sites, in which modifications of the epigenetic profile are associated with hypersexuality. The genome-wide methylation pattern was measured in whole blood using the Illumina Infinium Methylation EPIC BeadChip, measuring the methylation state of over 850 K CpG sites. Prior to analysis, the global DNA methylation pattern was pre-processed according to standard protocols and adjusted for white blood cell type heterogeneity. We included CpG sites located within 2000 bp of the transcriptional start site of the following HPA-axis coupled genes: Corticotropin releasing hormone (CRH), corticotropin releasing hormone binding protein (CRHBP), corticotropin releasing hormone receptor I (CRHR1), corticotropin releasing hormone receptor 2 (CRHR2), FKBP5 and the glucocorticoid receptor (NR3C1). We performed multiple linear regression models of methylation M-values to a categorical variable of hypersexuality, adjusting for depression, dexamethasone non-suppression status, Childhood Trauma Questionnaire total score and plasma levels of TNF-alpha and IL-6. Of 76 tested individual CpG sites, four were nominally significant (p<0.05), associated with the genes CRH, CRHR2 and NR3C1. Cg23409074-located 48 bp upstream of the transcription start site of the CRH gene - was significantly hypomethylated in hypersexual patients after corrections for multiple testing using the FDR-method. Methylation levels of cg23409074 were positively correlated with gene expression of the CRH gene in an independent cohort of 11 healthy male subjects. The methylation levels at the identified CRH site, cg23409074, were significantly correlated between blood and four different brain regions. CRH is an important integrator of neuroendocrine stress responses in the brain, with a key role in the addiction processes. Our results show epigenetic changes in the CRH gene related to hypersexual disorder in men.

Place, publisher, year, edition, pages
PERGAMON-ELSEVIER SCIENCE LTD , 2017. Vol. 80, 67-73 p.
Keyword [en]
Epigenetics, Methylation, HPA-axis, Hypersexual disorder, Neuroinflammation, TNF-alpha, Cortisol, Dexamethasone test, Childhood trauma
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-326213DOI: 10.1016/j.psyneuen.2017.03.007ISI: 000402352200009PubMedID: 28319850OAI: oai:DiVA.org:uu-326213DiVA: diva2:1120559
Funder
Swedish Research CouncilThe Swedish Brain FoundationVästerbotten County CouncilStockholm County Council
Available from: 2017-07-06 Created: 2017-07-06 Last updated: 2017-07-06Bibliographically approved

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Boström, Adrian E.Ciuculete, Diana-MariaSchiöth, Helgi B.
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