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Associations of monoamine oxidase A gene first exon methylation with sexual abuse and current depression in women
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden;Karolinska Univ Sjukhuset, Psychiat Bldg R5 00 C-O Jari Tiihonen, S-17176 Stockholm, Sweden.
Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.ORCID iD: 0000-0002-2174-2068
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.ORCID iD: 0000-0002-8853-2508
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2018 (English)In: Journal of neural transmission, ISSN 0300-9564, E-ISSN 1435-1463, Vol. 125, no 7, p. 1053-1064Article in journal (Refereed) Published
Abstract [en]

Childhood physical abuse (PA) and sexual abuse (SA) interact with monoamine oxidase A (MAOA) gene polymorphism to modify risk for mental disorders. In addition, PA and SA may alter gene activity through epigenetic mechanisms such as DNA methylation, thereby further modifying risk for disorders. We investigated whether methylation in a region spanning the MAOA first exon and part of the first intron was associated with PA and/or SA, MAOA genotype, alcohol dependence, drug dependence, depression disorders, anxiety disorders, and conduct disorder. 114 Swedish women completed standardized diagnostic interviews and questionnaires to report PA and SA, and provided saliva samples for DNA extraction. DNA was genotyped for MAOA-uVNTR polymorphisms, and methylation of a MAOA region of interest (chrX: 43,515,544-43,515,991) was measured. SA, not PA, was associated with hypermethylation of the MAOA first exon relative to no-abuse, and the association was robust to adjustment for psychoactive medication, alcohol and drug dependence, and current substance use. SA and MAOA-uVNTR genotype, but not their interaction, was associated with MAOA methylation. SA associated with all measured mental disorders. Hypermethylation of MAOA first exon mediated the association of SA with current depression, and both methylation levels and SA independently predicted lifetime depression. Much remains to be learned about the independent effects of SA and MAOA-uVNTR genotypes on methylation of the MAOA first exon.

Place, publisher, year, edition, pages
SPRINGER WIEN , 2018. Vol. 125, no 7, p. 1053-1064
Keywords [en]
Child abuse, Depression, Epigenetics, Gene-environment interaction methylation, Women
National Category
Psychiatry
Identifiers
URN: urn:nbn:se:uu:diva-358274DOI: 10.1007/s00702-018-1875-3ISI: 000435405600006PubMedID: 29600412OAI: oai:DiVA.org:uu-358274DiVA, id: diva2:1243054
Funder
Forte, Swedish Research Council for Health, Working Life and WelfareStockholm County CouncilThe Karolinska Institutet's Research FoundationAvailable from: 2018-08-30 Created: 2018-08-30 Last updated: 2018-08-30Bibliographically approved

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Checknita, DaveComasco, ErikaNilsson, Kent W.

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