| 1. |
- Checknita, David, et al.
(author)
-
Associations of monoamine oxidase A gene first exon methylation with sexual abuse and current depression in women
- 2018
-
In: Journal of neural transmission. - : SPRINGER WIEN. - 0300-9564 .- 1435-1463. ; 125:7, s. 1053-1064
-
Journal article (peer-reviewed)abstract
- 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.
|
|
| 2. |
- Checknita, Dave, et al.
(author)
-
Monoamine oxidase A genotype and methylation moderate the association of maltreatment and aggressive behaviour
- 2020
-
In: Behavioural Brain Research. - : ELSEVIER. - 0166-4328 .- 1872-7549. ; 382
-
Journal article (peer-reviewed)abstract
- Background: The association between childhood maltreatment and subsequent aggressive behaviour is modified by monoamine oxidase A (MAOA) functional polymorphism (MAOA-uVNTR) genotype, MAOA-Long (MAOA-L) in females, MAOA-Short (MAOA-S) in males. Childhood maltreatment is associated with differential DNA methylation in several genes. Consistent with recent proposals, we hypothesized that the association of the interaction of MAOA genotype and maltreatment with aggressive behaviour is further moderated by methylation of a region of interest (ROI) spanning the first exon and partial first intron of MAOA.Method: The sample included 117 women and 77 men who completed interviews and questionnaires to report maltreatment and aggressive behaviour towards others and provided saliva samples for DNA extraction. The MAOA-uVNTR polymorphism was genotyped, and methylation of the MAOA ROI was assessed.Results: Following adjustment for substance misuse, psychoactive medication use, and in males tobacco use, the highest levels of aggressive behaviour were found among maltreated male carriers of MAOA-S with high levels of exonic methylation.Conclusion: Methylation levels within the MAOA ROI further contributed to the interaction of MAOA risk genotypes and maltreatment on aggressive behaviours among men.
|
|
| 3. |
- Checknita, David, 1983-
(author)
-
The Monoamine Oxidase A Gene and Antisocial Outcomes : An Examination of Genetic, Epigenetic, and Environmental Factors
- 2021
-
Doctoral thesis (other academic/artistic)abstract
- Background. Antisocial behaviour involves violation of the basic rights of others or social norms or rules. Such behaviours are indexed in diagnoses such as conduct disorder (CD) in adolescence and antisocial personality disorder (ASPD) in adulthood, which are typified by comorbidity with mood, anxiety, and substance misuse disorders. Alcohol misuse is strongly associated with antisocial behaviour and persistent aggressive behaviours. How environmental and biological factors interface to modulate risk for these outcomes is not yet understood, however, the interaction of adversity with a variable number tandem repeat (uVNTR) polymorphism of the monoamine oxidase gene A (MAOA) gene associates with antisocial behaviour and mental disorders. Further, DNA methylation in a region of interest (ROI) spanning MAOA’s first exonic/intronic junction associates with ASPD in men as well as other mood, anxiety, and substance misuse disorders. Aim and Methods. We characterized methylation of the MAOA ROI by sex and age and examined how negative and positive environmental factors interact with MAOA genotype and methylation on antisocial phenotypes and mental disorders. Participants included men and women from a clinical population of young adults recruited in adolescence at a substance misuse clinic and a community sample of adolescents. Findings. (1) Sex but not age was associated with methylation levels such that high methylation levels among women likely represent X-chromosome inactivation, and sexual abuse was associated with hypermethylation of the MAOA first exon, (2) high methylation levels mediated associations between sexual abuse and current depression diagnosis in women, (3) the highest levels of aggressive behaviour were found among maltreat male carriers of the low-expressing MAOA-uVNTR allele and displayed high levels of exonic methylation, while no interactions were shown in women, and (4) among adolescent girls, but not boys, positive parent-child relationship attenuated the interaction of maltreatment and the high-expressing MAOA-uVNTR allele on alcohol consumption, though the interactions were not robust to adjustments for tobacco use, substance misuse, and delinquent behaviours.Conclusion. The findings presented here advance our understanding of how maltreatment interfaces with genotypic and epigenetic factors, in a sex-dependent manner, to promote aggressive behaviour and mental disorders among susceptible individuals.
|
|
