uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
The Interaction of MAOA-uVNTR Genotype, Maltreatment, and Positive Parent-child relationship Predicts Adolescent Alcohol Drinking in a Sex-Dependent Manner
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. Center for Clinical Research, Uppsala University, Västerås, Sweden. (Science for Life Laboratory)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. Center for Clinical Research, Uppsala University, Västerås, Sweden; Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
Center for Clinical Research, Uppsala University, Västerås, Sweden.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. (Science for Life Laboratory)
Show others and affiliations
(English)Manuscript (preprint) (Other academic)
Keywords [en]
MAOA, Maltreatment, Alcohol, Parent-child relationship
National Category
Medical and Health Sciences
Research subject
Medical Science
Identifiers
URN: urn:nbn:se:uu:diva-393297OAI: oai:DiVA.org:uu-393297DiVA, id: diva2:1352568
Available from: 2019-09-19 Created: 2019-09-19 Last updated: 2019-10-08
In thesis
1. Predictors of Alcohol Misuse: Role of MAOA Genotype, Methylation, Transcription, and Negative and Positive Environmental factors
Open this publication in new window or tab >>Predictors of Alcohol Misuse: Role of MAOA Genotype, Methylation, Transcription, and Negative and Positive Environmental factors
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Alcohol misuse is a risk factor for alcohol use disorder (AUD). Gene-environment interactions contribute to the risk or resilience for AUD. A functional polymorphism in the promoter of the monoamine oxidase A gene (MAOA-uVNTR), in interaction with negative environment (Eneg), is associated with alcohol misuse and AUD. Men carrying short (MAOA-S), and women carrying long (MAOA-L), MAOA-uVNTR alleles who experienced maltreatment or poor parent-child relationships are at increased susceptibility to alcohol misuse and AUD. This thesis assessed whether the association of MAOAxEneg with the risk of AUD is moderated by MAOA methylation or positive environment and whether MAOA methylation-associated changes in MAOA expression in the stress- and reward-related brain regions is an underlying mechanism.

The thesis reveals that the association of MAOAxEneg with alcohol misuse is moderated by MAOA methylation in men, but not in women. In the clinical sample, men carrying MAOA-S allele who experienced maltreatment and had low MAOA methylation displayed higher alcohol-related problems than those without maltreatment or MAOA-L carriers with and without maltreatment. Furthermore, the quality of the parent–child relationship moderated the association of MAOAxEneg with alcohol misuse in a sex- and AUD stage-dependent manner. In the non-clinical sample of adolescents, girls carrying MAOA-L allele who experienced maltreatment and poor parent–child relationship displayed higher alcohol consumption, whereas those with average or good parent–child relationship had lower alcohol consumption. In the clinical sample of adolescents, however, no such association was observed. These results suggest that a good parent–child relationship protects MAOA susceptibility genotype carriers exposed to maltreatment during the early stages of alcohol use. The preclinical studies revealed that the male rats exposed to Eneg and alcohol had higher CpG-specific Maoa promoter methylation, which was associated with lower Maoa expression in the nucleus accumbens than the control rats. Thus, MAOA methylation-associated changes in MAOA expression in the nucleus accumbens might mediate the effect of environment on alcohol use.

The thesis contributes to the understanding of biological mechanisms underlying MAOAxEnvironment effect and the critical role of MAOA methylation and positive environment in moderating risk and resilience for AUD. Also, the identification of subgroups may benefit from personalised interventions for AUD.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2019. p. 115
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1602
Keywords
Alcohol, AUD, MAOA, methylation, expression, early-life stress, maltreatment, parent–child relationship, gene–environment interactions.
National Category
Medical and Health Sciences
Research subject
Medical Science
Identifiers
urn:nbn:se:uu:diva-393306 (URN)978-91-513-0769-5 (ISBN)
Public defence
2019-11-27, Aulan, 21, Västmanlands Hospital, Västerås, 13:15 (English)
Opponent
Supervisors
Available from: 2019-11-06 Created: 2019-10-08 Last updated: 2019-11-27

Open Access in DiVA

No full text in DiVA

Search in DiVA

By author/editor
Bendre, Megha
By organisation
Department of Neuroscience
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar

urn-nbn

Altmetric score

urn-nbn
Total: 16 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf