| 21. |
- Checknita, David, et al.
(författare)
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Associations of monoamine oxidase A gene first exon methylation with sexual abuse and current depression in women
- 2018
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Ingår i: Journal of neural transmission. - : SPRINGER WIEN. - 0300-9564 .- 1435-1463. ; 125:7, s. 1053-1064
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Tidskriftsartikel (refereegranskat)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.
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| 22. |
- Checknita, Dave, et al.
(författare)
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Monoamine oxidase A genotype and methylation moderate the association of maltreatment and aggressive behaviour
- 2020
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Ingår i: Behavioural Brain Research. - : ELSEVIER. - 0166-4328 .- 1872-7549. ; 382
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Tidskriftsartikel (refereegranskat)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.
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| 23. |
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| 24. |
- Comasco, Erika, et al.
(författare)
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Adipocytokines levels at delivery, functional variation of TFAP2 beta, and maternal and neonatal anthropometric parameters
- 2013
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Ingår i: Obesity. - : Wiley. - 1930-7381 .- 1930-739X. ; 21:10, s. 2130-2137
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVEAdipocytokines participate in the regulation of glucose metabolism and foetal development. The transcription factor activating protein 2B (TFAP2β) has been associated with adipocytokine regulation, and gene variations with type 2 diabetes and obesity. This study investigated associations between maternal TFAP2B variation, adipocytokines levels and maternal and neonatal anthropometric characteristics.DESIGN AND METHODSA population-based sample of women was followed from delivery to six months postpartum. Adiponectin, leptin and interleukin-6 levels at delivery, and maternal as well as neonatal anthropometric variables were assessed. The TFAP2β intron 1 variable number tandem repeat (VNTR) was genotyped.RESULTSMaternal interleukin-6 correlated positively with leptin at delivery, with peripartum weight changes and weight of newborn males, adjusted for potential confounders. Leptin at delivery was associated with TFAP2β intron 1 VNTR genotype, adjusted for confounders, maternal weight and negatively with birth weight among female neonates. A path model suggested a link between TFAP2β genotype, leptin levels and newborn females' weight.CONCLUSIONSThe present results stress a role for the TFAP2 β in adiposity-related conditions and intrauterine growth. The association between neonatal birth weight and maternal adipocytokine levels, together with the observed sex effect, call for further studies on the mechanisms behind neuro-endocrine foetal programming.
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| 25. |
- Comasco, Erika, et al.
(författare)
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Adolescent alcohol consumption : Biomarkers PEth and FAEE in relation to interview and questionnaire data
- 2009
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Ingår i: Journal of Studies on Alcohol and Drugs. - : ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV. - 1937-1888 .- 1938-4114. ; 70:5, s. 797-804
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE The aim of this study was to investigate the congruence of biomarkers, questionnaires, and interviews as instruments to assess adolescent alcohol consumption. METHOD The methodology used was a cross-sectional study with a randomized sample. Four different methods were used to estimate high adolescent alcohol consumption. The concordance of the results was investigated. Surveys were performed, and biological specimens were collected at all schools in the county of Västmanland, Sweden, in 2001. Eighty-one boys and 119 girls from a population of 16- and 19-year-old adolescents were randomly selected from quartiles of volunteers representing various degrees of psychosocial risk behaviors. Using a questionnaire (for a 1-hour session) and in-depth interviews, subjects were assessed regarding their alcohol-use habits. Blood and hair samples were analyzed for phosphatidylethanol (PEth) and fatty acid ethyl esters (FAEEs), respectively. RESULTS High alcohol consumption was underreported in the questionnaire compared with the interviews. PEth and FAEE analyses weakly confirmed the self-reports, and the results of the two biochemical tests did not overlap. The PEth blood test was the most specific but the least sensitive, whereas the FAEE hair test revealed low specificity and an overrepresentation of positive results in girls. CONCLUSIONS The expected higher self-report of high alcohol consumption by interview rather than by questionnaire was confirmed partly because of the influence of a bogus pipeline procedure. The absence of overlap between PEth and FAEE results and their poor agreement with self-reports suggested that biomarkers are unsuitable as screening tools for alcohol consumption in adolescents.
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| 26. |
- Comasco, Erika, 1982-
(författare)
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Alcohol Consumption among Adolescents : Psychosocial and Genetic influences
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The present thesis is based on four studies focusing on alcohol consumption among Swedish adolescents, and therewith related psychosocial and genetic factors. One main objective was to study the reasons for drinking alcohol among different population - representative samples of adolescents in order to identify motives for drinking. Relationships between these drinking motives, alcohol consumption, and alcohol - related problems were also investigated. Three motives emerged from this study: social - enhancement, coping and dominance. The association with alcohol consumption and alcohol - related problems was positive for social - enhancement and coping motives, but negative for the dominance motive. A significant heritability of alcohol use disorders has been demonstrated by family, adoption and twin studies. Environmental influences have also been acknowledged to play an important role in the development of alcohol use disorders. Moreover, the interaction between genetic and environmental factors is likely to influence the risk - resilience for alcohol use disorders. In view of this knowledge, plausible candidate polymorphisms were considered in gene - environment interaction models. An effect of the genetic polymorphisms was only present when a G x E model was considered. A genetic variant of the clock gene Period2, in an interaction with sleep problems, was studied in relation to alcohol consumption among adolescents. High alcohol consumption was associated with the AA genotype of the PER2 SNP10870 polymorphism, in an interaction with several and frequent sleep problems, among adolescent boys. A genetic variant in the opioid µ receptor 1 gene, in an interaction with alcohol consumption, was studied in relation to depressive symptoms. Depressive symptoms were predicted by the G allele of the OPRM1 A118G polymorphism, in an interaction with high alcohol consumption, among adolescent girls. Additionally, the PER2 SNP10870 and the OPRM1 A118G polymorphisms were studied in a sample of severely alcoholic females. Furthermore, alcohol consumption was assessed by using different instruments, such as biomarkers and surveys. Comparisons were carried out to identify the most suitable method to assess alcohol consumption among adolescents. Questionnaire and interview seemed more suitable tools than biomarkers in this regard.The results eventually support the importance of psychosocial and genetic influences, and their interaction effect on alcohol consumption among adolescents.
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| 27. |
- Comasco, Erika, et al.
(författare)
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Alcohol Consumption Among Pregnant Women in a Swedish Sample and Its Effects on the Newborn Outcomes
- 2012
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Ingår i: Alcoholism. - : Wiley. - 0145-6008 .- 1530-0277. ; 36:10, s. 1779-1786
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Tidskriftsartikel (refereegranskat)abstract
- Background Little is known about the effects of low levels of maternal alcohol intake on the neuropsychological development of the child. This study is part of an ongoing investigation on maternal drinking and presents data on demographic variables, maternal alcohol use, and birth outcomes from that study. Methods The sample comprised 2,264 women from a Swedish antenatal clinic. Retrospective self-report data were collected on alcohol consumption before and during pregnancy, using the Alcohol Use Disorders Identification Test (AUDIT), and on nicotine use. Specific alcohol biomarkers for excessive drinking, carbohydrate-deficient transferrin (CDT) in serum and phosphatidylethanol (PEth) in whole blood, were determined during mid-pregnancy in a subsample of the women. Data on labor and early characteristics of the child were also assessed. Results Before pregnancy, 89% of the women regularly consumed alcohol and 49% reported occasional or frequent binge drinking. Nicotine was used by 15% before and by 5% during pregnancy. During pregnancy, 12% continued using alcohol and 5% also admitted binge drinking. However, all alcohol biomarker values were below the reporting limits (CDT = 1.7% disialotransferrin; total PEth < 0.1 mu mol/L). Self-reported drinking during pregnancy was associated with a higher AUDIT score before pregnancy, nicotine use at the time of the first prenatal visit, older age, and previous legal abortions. Conclusions The AUDIT questionnaire and 2 specific alcohol biomarkers were used in routine maternity care to collect information about drinking during pregnancy and thereby to identify children at risk for alcohol-related complications. While the AUDIT results suggested that a significant number of women continued using alcohol during pregnancy, implying a risk for fetal disorders, the biomarkers showed negative test values thus indicating only modest drinking levels.
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| 28. |
- Comasco, Erika, et al.
(författare)
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Alpha 2a-Adrenoceptor Gene Expression and Early Life Stress-Mediated Propensity to Alcohol Drinking in Outbred Rats
- 2015
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1661-7827 .- 1660-4601. ; 12:7, s. 7154-7171
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Tidskriftsartikel (refereegranskat)abstract
- Stressful events early in life, later high alcohol consumption and vulnerability to alcohol use disorder (AUD) are tightly linked. Norepinephrine is highly involved in the stress response and the alpha 2A-adrenoceptor, which is an important regulator of norepinephrine signalling, is a putative target in pharmacotherapy of AUD. The aim of the present study was to investigate the effects of early-life stress and adult voluntary alcohol drinking on the alpha 2A-adrenoceptor. The relative expression and promoter DNA methylation of the Adra2a gene were measured in the hypothalamus, a key brain region in stress regulation. A well-characterized animal model of early-life stress was used in combination with an episodic voluntary drinking in adulthood. Alcohol drinking rats with a history of early-life stress had lower Adra2a expression than drinking rats not exposed to stress. Alcohol intake and Adra2a gene expression were negatively correlated in high-drinking animals, which were predominantly rats subjected to early-life stress. The results provide support for a link between early-life stress, susceptibility for high alcohol consumption, and low Adra2a expression in the hypothalamus. These findings can increase our understanding of the neurobiological basis for vulnerability to initiate risk alcohol consumption and individual differences in the response to 2A-adrenoceptor agonists.
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| 29. |
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| 30. |
- Comasco, Erika, 1982-, et al.
(författare)
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Constitutive serotonin transporter reduction resembles maternal separation with regard to stress-related gene expression
- 2019
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Ingår i: ACS Chemical Neuroscience. - : American Chemical Society (ACS). - 1948-7193. ; 10:7, s. 3132-3142
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Tidskriftsartikel (refereegranskat)abstract
- Interactive effects between allelic variants of the serotonin transporter (5-HTT) promoter-linked polymorphic region (5-HTTLPR) and stressors on depression symptoms have been documented, as well as questioned, by meta-analyses. Translational models of constitutive 5-htt reduction and experimentally controlled stressors often led to inconsistent behavioral and molecular findings and often did not include females. The present study sought to investigate the effect of 5-htt genotype, maternal separation, and sex on the expression of stress-related candidate genes in the rat hippocampus and frontal cortex. The mRNA expression levels of Avp, Pomc, Crh, Crhbp, Crhr1, Bdnf, Ntrk2, Maoa, Maob, and Comt were assessed in the hippocampus and frontal cortex of 5-htt± and 5-htt+/+ male and female adult rats exposed, or not, to daily maternal separation for 180 min during the first 2 postnatal weeks. Gene- and brain region-dependent, but sex-independent, interactions between 5-htt genotype and maternal separation were found. Gene expression levels were higher in 5-htt+/+ rats not exposed to maternal separation compared with the other experimental groups. Maternal separation and 5-htt+/− genotype did not yield additive effects on gene expression. Correlative relationships, mainly positive, were observed within, but not across, brain regions in all groups except in non-maternally separated 5-htt+/+ rats. Gene expression patterns in the hippocampus and frontal cortex of rats exposed to maternal separation resembled the ones observed in rats with reduced 5-htt expression regardless of sex. These results suggest that floor effects of 5-htt reduction and maternal separation might explain inconsistent findings in humans and rodents.
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