| 1. |
- Andreou, Dimitrios, et al.
(författare)
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Maltreatment, the Oxytocin Receptor Gene, and Conduct Problems Among Male and Female Teenagers
- 2018
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Ingår i: Frontiers in Human Neuroscience. - : FRONTIERS MEDIA SA. - 1662-5161. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- The oxytocin receptor gene (OXTR) influences human behavior. The G allele of OXTR rs53576 has been associated with both prosocial and maladaptive behaviors but few studies have taken account of environmental factors. The present study determined whether the association of childhood maltreatment with conduct problems was modified by OXTR rs53576 genotypes. In a general population sample of 1591 teenagers, conduct problems as well as maltreatment were measured by self-report. DNA was extracted from saliva samples. In males, there was a significant positive association between maltreatment and conduct problems independent of the genotype. In females, among G allele carriers, the level of conduct problems was significantly higher among those who had been maltreated as compared to those not maltreated. By contrast, among female AA carriers, conduct problems did not vary between those who were, and who were not, maltreated. The results indicate that OXTR rs53576 plays a role in antisocial behavior in females such that the G allele confers vulnerability for antisocial behavior if they experience maltreatment, whereas the A allele has a protective effect.
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| 2. |
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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. |
- Isaksson, Johan, et al.
(författare)
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Associations between the FKBP5 haplotype, exposure to violence and anxiety in females
- 2016
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Ingår i: Psychoneuroendocrinology. - Oxford, United Kingdom : Elsevier. - 0306-4530 .- 1873-3360. ; 72, s. 196-204
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Tidskriftsartikel (refereegranskat)abstract
- The gene that encodes the FK506-binding protein 5 (FKBP5) is regarded as a candidate for investigating how negative life events interact with a genetic predisposition to stress-related disorders, such as depression and anxiety. Given the role of FKBP5 as an important regulator of stress responses, we aimed to investigate if single-nucleotide polymorphisms (SNPs) in FKBP5-in the presence/absence of exposure to violence-are associated with symptoms of depression and anxiety. Data from two community-based samples of adolescents (n=1705) and young adults (n=1800) regarding ratings on depression, anxiety, exposure to violence and FKBP5 genotype were collected. A risk haplogenotype including the minor alleles of seven common SNPs in the FKBP5 (rs3800373, rs9296158, rs7748266, rs1360780, rs9394309, rs9470080 and rs4713916) conferred higher ratings on anxiety among females, but not males, in the presence of violence. Exposure to violence and female sex were associated with higher ratings on both depression and anxiety, with the exception of ratings on depression among young adults, on which sex had no effect. Ratings on depression were not associated with the haplogenotype. These findings may correspond to differences in the regulation of the HPA axis and with the higher vulnerability to anxiety in females.
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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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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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| 8. |
- 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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| 9. |
- Olofsdotter, Susanne, et al.
(författare)
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Differential susceptibility effects of oxytocin gene (OXT) polymorphisms and perceived parenting on social anxiety among adolescents
- 2018
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Ingår i: Development and psychopathology (Print). - : CAMBRIDGE UNIV PRESS. - 0954-5794 .- 1469-2198. ; 30:2, s. 449-459
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Tidskriftsartikel (refereegranskat)abstract
- Social anxiety is one of the most commonly reported mental health problems among adolescents, and it has been suggested that parenting style influences an adolescent's level of anxiety. A context-dependent effect of oxytocin on human social behavior has been proposed; however, research on the oxytocin gene (OXT) has mostly been reported without considering contextual factors. This study investigated the interactions between parenting style and polymorphic variations in the OXT gene in association with social anxiety symptoms in a community sample of adolescents (n = 1,359). Two single nucleotide polymorphisms linked to OXT, rs4813625 and rs2770378, were genotyped. Social anxiety and perceived parenting style were assessed by behavioral questionnaires. In interaction models adjusted for sex, significant interaction effects with parenting style were observed for both variants in relation to social anxiety. The nature of the interactions was in line with the differential susceptibility framework for rs4813625, whereas for rs2770378 the results indicated a diathesis–stress type of interaction. The findings may be interpreted from the perspective of the social salience hypothesis of oxytocin, with rs4813625 affecting social anxiety levels along a perceived unsafe–safe social context dimension.
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| 10. |
- Olofsdotter, Susanne, et al.
(författare)
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Interaction between oxytocin gene variants and perceived parenting in relation to social anxiety in adolescents : Evidence for differential susceptibility effects
- 2017
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Ingår i: European psychiatry. - : Cambridge University Press (CUP). - 0924-9338 .- 1778-3585. ; 41, s. S72-S72
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Adolescence is a period of increasing demands in independent social functioning where parenting style may have an impact on social anxiety. A context-dependent effect of oxytocin on human social behavior has been suggested, however research on the gene coding for oxytocin (OXT) has mostly been reported without considering contextual factors.AimThis study investigated interactions between parenting style and polymorphic variations in the OXT gene in association with social anxiety symptoms in a community sample of adolescents.MethodsThe study group consisted of 1359 adolescents. Two single nucleotide polymorphisms located near OXT, rs4813625 and rs2770378, were genotyped. Social anxiety and perceived parenting style were assessed by behavioral questionnaires.ResultsSignificant joint effects in line with the differential susceptibility framework were observed for rs4813625 with parenting style. The levels of social anxiety among C allele carriers were conditional on the level of supportive parenting style whereas homozygote G carriers’ levels of social anxiety were unaffected by supportive parenting style. The nature of the interactions between rs2770378 and parenting style was in line with the diatheses-stress model. However, associations of rs2770378 and parenting style with social anxiety became nonsignificant in nonlinear models.ConclusionsThe study provides preliminary evidence for a modifying effect of supportive parenting style on the relationship between rs4813625 and social anxiety symptoms in adolescents, independent of sex. The findings may be interpreted from the perspective of the social salience hypotheses of oxytocin, with rs4813625 affecting social anxiety levels along a perceived unsafe–safe social context dimension.Disclosure of interestThe authors have not supplied their declaration of competing interest.
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