| 1. |
- Gokturk, Camilla, et al.
(författare)
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Serotonin transporter (5-HTTLPR) and monoamine oxidase (MAOA) promoter polymorphisms in women with severe alcoholism
- 2008
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Ingår i: Archives of Women's Mental Health. - : Springer Science and Business Media LLC. - 1434-1816 .- 1435-1102. ; 11:5-6, s. 347-355
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Tidskriftsartikel (refereegranskat)abstract
- The serotonin system is known to play a pivotal role for mood, behaviour and psychic illness as e.g. alcoholism. Alcoholism in both males and females has been associated with polymorphisms in genes encoding for proteins of importance for central serotonergic function. Genotyping of two functional polymorphisms in the promoter region of the serotonin transporter and monoamine oxidase-A, respectively, (5-HTT-LPR and MAOA-VNTR), was performed in a group of women with severe alcohol addiction. A large sample of adolescent females from a normal population was used as controls. A significantly higher frequency of the LL 5-HTT genotype (high activity) was found in female addicts without a known co-morbid psychiatric disorder than in the controls. Genotype of the MAOA-VNTR polymorphism did not differ significantly between addicts and controls. However, within the group of alcoholics, when the patients with known co-morbid psychiatric disorders were excluded, aggressive anti-social behaviour was significantly linked to the presence of the high activity MAOA allele. The pattern of associations between genotypes of 5-HTT-LPR and MAOA-VNTR in women with severe alcoholism differs from most corresponding studies on males.
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| 2. |
- 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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| 3. |
- Comasco, Erika, et al.
(författare)
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The clock gene PER2 and sleep problems : association with alcohol consumption among Swedish adolescents
- 2010
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Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 115:1, s. 41-48
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Alcohol abuse is associated with sleep problems, which are often linked to circadian rhythm disturbances. Previous studies have separately examined the effects of mutations in the clock gene PER2 on alcohol consumption and sleep problems. Here we hypothesized that an allelic variation in the PER2 gene is associated with alcohol consumption in interaction with sleep problems among adolescents. METHODS: The Survey of Adolescent Life and Health in Västmanland 2006, a Swedish county, including 1254 students 17-18 years old, was used as a population-representative sample of adolescents. We investigated the PER2 Single Nucleotide polymorphism (SNP) 10870 (A/G) in the cohort together with an assessment of alcohol consumption according to the AUDIT-C questionnaire, and sleep problems using a survey consisting of 18 items. Furthermore, we carried out an exploratory analysis on the PER2 Single Nucleotide Polymorphism 10870 polymorphism in a group of severely alcoholic females. RESULTS: We found a significant association of the SNP 10870 in adolescent boys, where the genotype AA, in the presence of several and frequent sleep problems, was associated with increased alcohol consumption. Among adolescent girls, only sleep problems were related to alcohol consumption. A non-significant trend was observed among the severely alcoholic females, with the G allele being over-represented in the severely alcoholic females group in comparision to the control females. CONCLUSION: These results indicate that PER2 gene variation is associated with alcohol consumption in interaction with sleep problems among Swedish adolescent boys.
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| 4. |
- Comasco, Erika, et al.
(författare)
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Three-way interaction effect of 5-HTTLPR, BDNF Val66Met, and childhood adversity on depression : A replication study
- 2013
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Ingår i: European Neuropsychopharmacology. - : ELSEVIER. - 0924-977X .- 1873-7862. ; 23:10, s. 1300-1306
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Tidskriftsartikel (refereegranskat)abstract
- Both the serotonin transporter linked promoter region (5-HTTLPR) and the brain-derived neurotrophic factor (BDNF) Val66Met polymorphisms have been shown to interact with unfavourable environment in relation to depression symptoms and to depression diagnosis. Several attempts have been made to study a three-way interaction effect of these factors on depression, however with contradictory results. We aimed to test the hypothesis of a three-way interaction effect and to attempt at replication in an independent population-based sample. Family maltreatment, sexual abuse and depression were self-reported by an adolescent population-based cohort (N=1393) from the county of Vastmanland, Sweden. DNA was isolated from saliva, and used for genotyping of the 5-HTTLPR and BDNF Val66Met polymorphisms. Neither 5-HTTLPR or BDNF genotypes separately, nor in interaction with each other had any relation to depression, however in an environment adjusted model a two-way interaction and a three-way interaction effect was found. Both 5-HTTLPR and BDNF Val66Met interacted with unfavourable environment in relation to depressive symptoms (Adj R-2=0.19). Depressive symptoms and depression were more common among carriers of either the ss/sl+Val/Val or the ll+Met genotypes in the presence of early-life adversities. This three-way effect was more pronounced among girls. The current study, with a virtually similar set-up compared to previous studies, can partially confirm previous findings and their generalizability. The study also shows the importance of genetic plasticity in individuals with different environmental exposure, for different phenotypic expression.
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| 5. |
- Comasco, Erika, et al.
(författare)
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Why Do Adolescents Drink? : Motivational Patterns Related to Alcohol Consumption and Alcohol-Related Problems
- 2010
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Ingår i: Substance Use & Misuse. - : Informa UK Limited. - 1082-6084 .- 1532-2491. ; 45:10, s. 1589-1604
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Tidskriftsartikel (refereegranskat)abstract
- The present study was designed to investigate motivational patterns for drinking alcohol and their relation about alcohol consumption and problems related to alcohol consumption. Data were collected by semistructured interviews and questionnaires, containing questions about reasons for drinking, alcohol consumption, and problems related to alcohol consumption during the years 2001, 2004, and 2005. Three independent population samples from two different counties of central Sweden were included. A total of 11,167 adolescents participated. Data on reasons for drinking were analyzed by factor analysis to extract components explaining drinking motives. Relationships between motivational patterns and alcohol use were examined with correlation analysis. Three drinking motives emerged (social-enhancement, coping, and dominance motives) and related to alcohol consumption and problems related to alcohol consumption. Limitations of the study are noted and discussed.
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| 6. |
- Nilsson, Kent W., et al.
(författare)
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Gene-environment interaction of monoamine oxidase A in relation to antisocial behaviour : current and future directions.
- 2018
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Ingår i: Journal of neural transmission. - : Springer Science and Business Media LLC. - 0300-9564 .- 1435-1463. ; 125:11, s. 1601-1626
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Forskningsöversikt (refereegranskat)abstract
- Since the pioneering finding of Caspi and co-workers in 2002 that exposure to childhood maltreatment predicted later antisocial behaviour (ASB) in male carriers of the low-activity MAOA-uVNTR allele, frequent replication studies have been published. Two meta-analyses, one in 2006 and the other in 2014, confirmed the original findings by Caspi and co-workers. In the present paper, we review the literature, note some methodological aspects of candidate gene–environment interaction (cG×E) studies and suggest some future directions. Our conclusions are as follows. (1) The direction of the effect in a cG×E model may differ according to the positive and negative environmental background of the population. (2) There is a predictor-intersection problem such that when measuring one type of maltreatment in a person, other kinds of maltreatment often co-occur. Other forms of abuse are implicitly considered in statistical models; therefore, it is difficult to draw conclusions about the effects of timing and the severity of different forms of stressful life events in relation to ASB. (3) There is also an outcome-intersection problem because of the major intersection of ASB and other forms of mental health problems. It is likely that the G×E with MAOA is related to a common unmeasured factor. (4) For the G×E model, in which the effect of the gene on the outcome variable is dependent on other predictor variables, theoretically, hypothesis-driven statistical modelling is needed.
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| 7. |
- Nilsson, Kent W., et al.
(författare)
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Genes encoding for AP-2beta and the Serotonin Transporter are associated with the Personality Character Spiritual Acceptance
- 2007
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Ingår i: Neuroscience Letters. - Uppsala Univ, Cent Hosp Vasteras 1, Ctr Clin Res, SE-72189 Vasteras, Sweden. Uppsala Univ, Dept Neurosci, BMC, SE-75124 Uppsala, Sweden. Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden. Lund Univ, Univ Hosp Malmo, Forens Psychiat Clin, SE-20502 Malmo, Sweden. : Elsevier BV. - 0304-3940 .- 1872-7972. ; 411:3, s. 233-237
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Tidskriftsartikel (refereegranskat)abstract
- In several twin studies the relative contribution of genetic factors for personality traits has amounted to figures between 40 and 60%. In the present study we investigated to which degree polymorphisms in the 5-HTT and AP-2beta genes are implicated in the neural processes involved in the formation of Temperament and Character traits, as estimated by Cloninger's TCI. Considering the background of previous reports, associations with the character Self-Transcendence and its sub-scale Spiritual Acceptance in particular, were of interest. A stratified random sample of 200 individuals (total population=5173), matched for age, gender and risk behaviors, from volunteering 16- and 19-year-old adolescents students in Sweden was investigated. Cloninger's TCI inventory was used for investigation of temperament and character traits. Blood samples were used for analyses of a promoter serotonin transporter polymorphism (5-HTTLPR) and an intron 2 polymorphism in the transcription factor AP-2beta gene. Among boys individuals with presence of the short 5-HTTLPR genotype showed lower scores, whereas individuals with presence of the short AP-2beta genotype showed higher scores of personality character Self-Transcendence and its sub-scale Spiritual Acceptance. Among girls no effect of either genotype was found. Both among boys and girls, significant interactive effects were found between 5-HTTLPR and AP-2beta genotypes, with regard to Self-Transcendence and Spiritual acceptance. Boys and girls with the combination of presence of the short 5-HTTLPR, and homozygosity for the long AP-2beta genotype scored significantly lower on Self-Transcendence and Spiritual Acceptance.
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| 8. |
- Nilsson, Kent W., et al.
(författare)
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Genotypes Do Not Confer Risk For Delinquency ut Rather Alter Susceptibility to Positive and Negative Environmental Factors : Gene-Environment Interactions of BDNF Val66Met, 5-HTTLPR, and MAOA-uVNTR
- 2015
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Ingår i: International Journal of Neuropsychopharmacology. - : OXFORD UNIV PRESS. - 1461-1457 .- 1469-5111. ; 18:5
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Tidskriftsartikel (refereegranskat)abstract
- Background: Previous evidence of gene-by-environment interactions associated with emotional and behavioral disorders is contradictory. Differences in findings may result from variation in valence and dose of the environmental factor, and/or failure to take account of gene-by-gene interactions. The present study investigated interactions between the brain-derived neurotrophic factor gene (BDNF Val66Met), the serotonin transporter gene-linked polymorphic region (5-HTTLPR), the monoamine oxidase A (MAOA-uVNTR) polymorphisms, family conflict, sexual abuse, the quality of the child-parent relationship, and teenage delinquency. Methods: In 2006, as part of the Survey of Adolescent Life in Vastmanland, Sweden, 1 337 high-school students, aged 1718 years, anonymously completed questionnaires and provided saliva samples for DNA analyses. Results: Teenage delinquency was associated with two-, three-, and four-way interactions of each of the genotypes and the three environmental factors. Significant four-way interactions were found for BDNF Val66Met x 5-HTTLPRxMAOA-uVNTR x family conflicts and for BDNF Val66Met x 5-HTTLPRxMAOA-uVNTR x sexual abuse. Further, the two genotype combinations that differed the most in expression levels (BDNF Val66Met Val, 5-HTTLPR LL, MAOA-uVNTR LL [girls] and L [boys] vs BDNF Val66Met Val/Met, 5-HTTLPR S/LS, MAOA-uVNTR S/SS/LS) in interaction with family conflict and sexual abuse were associated with the highest delinquency scores. The genetic variants previously shown to confer vulnerability for delinquency (BDNF Val66Met Val/Met x 5-HTTLPR S x MAOA-uVNTR S) were associated with the lowest delinquency scores in interaction with a positive child-parent relationship. Conclusions: Functional variants of the MAOA-uVNTR, 5-HTTLPR, and BDNF Val66Met, either alone or in interaction with each other, may be best conceptualized as modifying sensitivity to environmental factors that confer either risk or protection for teenage delinquency.
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| 9. |
- Nilsson, Kent W, et al.
(författare)
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Interaktioner mellan gener och miljö. Predicerar kriminalitet, depression och alkoholberoende
- 2006
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Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 103:39, s. 2859-2863
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Tidskriftsartikel (refereegranskat)abstract
- Recently interactions between promoter polymorphisms in the serotonin transporter gene and the Monoamine oxidase-A gene have been found to interact with psychosocial factors to predict outcome such as adolescent criminal behaviour, alcohol consumption and depression. In this paper we review this emerging field of scientific inquiry with particular attention paid to findings made on a population based sample of 119 girls and 81 boys from the county of Västmanland, Sweden.
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| 10. |
- Nilsson, Kent W., et al.
(författare)
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MAOA genotype, family relations and sexual abuse in relation to adolescent alcohol consumption
- 2011
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Ingår i: Addiction Biology. - : Wiley. - 1355-6215 .- 1369-1600. ; 16:2, s. 347-355
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the present study was to investigate MAOA gene-environment (G*E) interactions in relation to adolescent alcohol consumption. In the county of Vastmanland, Sweden, all 17-18-year-old students were asked to complete an anonymous questionnaire and provide a saliva sample during class hours. A total of 2263 students completed the questionnaire (77.4%) and a saliva sample was provided by 2131 participants. Failed MAOA u-variable number of tandem repeats (VNTR) genotype analyses and internal non-responses left 851 boys and 735 girls (total n = 1586) to be investigated. Alcohol use disorder identification test was used to measure hazardous alcohol consumption. MAOA u-VNTR was used to measure biological risk in interaction with poor family relations and experience of sexual abuse. The model was also adjusted for non-independent socioeconomic variables, separated parents, type of housing and parental unemployment. Results showed that the MAOA u-VNTR, in interaction with psychosocial risk factors, such as the quality of family relations and sexual abuse, was related to high alcohol consumption among adolescents. Girls, carrying the long MAOA u-VNTR variant showed a higher risk of being high alcohol consumers, whereas among boys, the short allele was related to higher alcohol consumption. The present study supports the hypothesis that there is a relation between MAOA u-VNTR and alcohol consumption and that this relation is modulated by environmental factors. Furthermore, the present study also supports the hypothesis that there is a sex difference in the G*E interaction.
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