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| 2. |
- Bergman, Olle, 1978, et al.
(författare)
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Study on the possible association of brain-derived neurotrophic factor polymorphism with the developmental course of symptoms of attention deficit and hyperactivity
- 2011
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Ingår i: International Journal of Neuropsychopharmacology. - New York, USA : Cambridge University Press. - 1461-1457 .- 1469-5111. ; 14:10, s. 1367-1376
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Tidskriftsartikel (refereegranskat)abstract
- Several studies have, with conflicting results, investigated the relationship between the Val⁶⁶Met polymorphism in brain-derived neurotrophic factor (BDNF) and attention deficit hyperactivity disorder (ADHD). We assessed longitudinal, quantitative phenotypes of hyperactivity-impulsivity and inattention in order to determine whether the Val⁶⁶Met polymorphism is associated with age-specific and/or persistent symptoms of hyperactivity-impulsivity and/or inattention in a community-based cohort of 1236 Swedish individuals for which ADHD symptom data were collected when the participants were aged 8-9, 13-14 and 16-17 yr. The Met allele was associated with symptoms of ADHD at ages 8-9 and 13-14 yr. A multivariate regression analysis revealed that the observed effect of the Met allele on ADHD symptoms reflects an influence on persistent hyperactivity-impulsivity symptoms. The present findings support the hypothesis that BDNF is involved in the pathogenesis of ADHD. The results highlight the importance of distinguishing between hyperactivity-impulsivity and inattention, respectively, and demonstrate the value of using a longitudinal approach in genetic studies of ADHD symptoms.
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| 3. |
- Johansson, Daniel, et al.
(författare)
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Associations between oxytocin-related genes and autistic-like traits
- 2014
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Ingår i: Social Neuroscience. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 1747-0919 .- 1747-0927.
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Tidskriftsartikel (refereegranskat)abstract
- Oxytocin has repeatedly been shown to influence human behavior in social contexts; also, a relationship between oxytocin and the pathophysiology of autism spectrum disorder (ASD) has been suggested. In the present study, we investigated single-nucleotide polymorphisms (SNPs) in the oxytocin gene (OXT) and the genes for single-minded 1 (SIM1), aryl hydrocarbon receptor nuclear translocator 2 (ARNT2) and cluster of differentiation 38 (CD38) in a population of 1771 children from the Child and Adolescent Twin Study in Sweden (CATSS). Statistical analyses were performed to investigate any association between SNPs and autistic-like traits (ALTs), measured through ASD scores in the Autism-Tics, ADHD and other Co-morbidities inventory. Firstly, we found a statistically significant association between the SIM1 SNP rs3734354 (Pro352Thr) and scores for language impairment (p = .0004), but due to low statistical power this should be interpreted cautiously. Furthermore, nominal associations were found between ASD scores and SNPs in OXT, ARNT2 and CD38. In summary, the present study lends support to the hypothesis that oxytocin and oxytocin neuron development may have an influence on the development of ALTs and suggests a new candidate gene in the search for the pathophysiology of ASD.
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| 4. |
- Jonsson, Lina, 1982, et al.
(författare)
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Association between ASMT and autistic-like traits in children from a Swedish nationwide cohort
- 2014
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Ingår i: Psychiatric Genetics. - Stockholm : Lippincott Williams & Wilkins. - 0955-8829 .- 1473-5873. ; 24:1, s. 21-27
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Tidskriftsartikel (refereegranskat)abstract
- Individuals with autism spectrum disorders often show low levels of melatonin, and it has been suggested that this decrease may be because of the low activity of the acetylserotonin O-methyltransferase (ASMT), the last enzyme in the melatonin-synthesis pathway. Also, genetic variants in ASMT have been associated with autism, as well as with low ASMT activity and melatonin levels, suggesting that the low ASMT activity observed in autism may partly be because of variations within the ASMT gene. In this study, we present a symptom-based approach to investigate possible associations between ASMT and autistic-like traits in the general population. To this end, continuous measures of autistic-like traits were assessed in a nationally representative twin cohort (n=1771) from Sweden and six single nucleotide polymorphisms (SNPs), and a duplication of exons 2-8 in ASMT were genotyped. Our results show a nominally significant association, in girls, between one single nucleotide polymorphism (rs5949028) in the last intron of ASMT and social interaction impairments. No significant association, however, was observed with traits related to language impairment or restricted and repetitive behavior. In conclusion, our results support the possible involvement of the ASMT gene in autism spectrum disorders, and our finding that only one of the three traits shows association suggests that genetic research may benefit from adopting a symptom-specific approach to identify genes involved in autism psychopathology.
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| 5. |
- Jonsson, Lina, 1982, et al.
(författare)
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Association study between autistic-like traits and polymorphisms in the autism candidate regions RELN, CNTNAP2, SHANK3, and CDH9/10
- 2014
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Ingår i: Molecular Autism. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 2040-2392.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Autistic-like traits (ALTs) are continuously distributed in the general population, with the autism spectrum disorder (ASD) at the upper extreme end. A genetic overlap has been shown between ALTs and ASD, indicating that common variation in ASD candidate genes may also influence ALTs. In our study, we have investigated the SNP rs4307059 that has been associated with both ALTs and ASD. In addition, we genotyped polymorphisms in a selection of genes involved in synaptic functioning, that is, SHANK3, RELN, and CNTNAP2, which repeatedly have been associated with ASD. The possible associations of these polymorphisms with ALTs, as well as genetic factors for neurodevelopmental problems (NDPs), were investigated in a large cohort from the general population: The Child and Adolescent Twin Study in Sweden. For analyses of ALTs and NDPs, 12,319 subjects (including 2,268 monozygotic (MZ) and 3,805 dizygotic (DZ) twin pairs) and 8,671 subjects (including 2,243 MZ and 2,044 DZ twin pairs), respectively, were included in the analyses. Findings: We could not replicate the previous association between rs4307059 and social communication impairment. Moreover, common variations in CNTNAP2 (rs7794745 and rs2710102), RELN (rs362691), and SHANK3 (rs9616915) were not significantly associated with ALTs in our study. Conclusions: Our results do not suggest that the investigated genes, which previously has been found associated with ASD diagnosis, have any major influence on ALTs in children from the general population.
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| 6. |
- Vestlund, Jesper, et al.
(författare)
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Ghrelin and aggressive behaviours—Evidence from preclinical and human genetic studies
- 2019
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530 .- 1873-3360. ; 104, s. 80-88
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Tidskriftsartikel (refereegranskat)abstract
- © 2019 Aggressive behaviour is of crucial importance in the defence for limited resources including food and mates and involves central serotonin as well as dopamine signalling. As ghrelin modulates food intake and sexual behaviour we initially investigated the hypothesis that central ghrelin signalling regulates aggressive behaviour in the resident intruder paradigm in male mice. Moreover, interaction between ghrelin signalling and serotonergic, noradrenergic as well as dopaminergic neurotransmission in aggression was investigated. The relevance of ghrelin for human aggression per se as well as for aggression induced by alcohol was evaluated in a human genetic association study comprising young men (n = 784) from the normal population assessed for anti-social behaviours. The present study demonstrates that central ghrelin infusion, but not ghrelin administered systemically, increases aggression. Moreover aggressive behaviour is decreased by pharmacological suppression of the growth hormone secretagogue receptor-1 A (GHSR-1A) by JMV2959. As indicated by the ex vivo biochemical data serotonin, rather than dopamine or noradrenaline, in amygdala may have central roles for the ability of JMV2959 to reduce aggression. This link between central serotonin, GHSR-1A and aggression is further substantiated by the behavioural data showing that JMV2959 cannot decrease aggression following depletion of central serotonin signalling. The genetic association study demonstrates that males carrying the Leu72Leu genotype of the pre-pro-ghrelin gene and displaying hazardous alcohol use are more aggressive when compared to the group carrying the Met-allele. Collectively, this contributes to the identification of central ghrelin pathway as an important modulator in the onset of aggressive behaviours in male mice.
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| 7. |
- Walum, Hasse, et al.
(författare)
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Genetic variation in the vasopressin receptor 1a gene (AVPR1A) associates with pair-bonding behavior in humans.
- 2008
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 105:37, s. 14153-14156
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Tidskriftsartikel (refereegranskat)abstract
- Pair-bonding has been suggested to be a critical factor in the evolutionary development of the social brain. The brain neuropeptide arginine vasopressin (AVP) exerts an important influence on pair-bonding behavior in voles. There is a strong association between a polymorphic repeat sequence in the 5' flanking region of the gene (avpr1a) encoding one of the AVP receptor subtypes (V1aR), and proneness for monogamous behavior in males of this species. It is not yet known whether similar mechanisms are important also for human pair-bonding. Here, we report an association between one of the human AVPR1A repeat polymorphisms (RS3) and traits reflecting pair-bonding behavior in men, including partner bonding, perceived marital problems, and marital status, and show that the RS3 genotype of the males also affects marital quality as perceived by their spouses. These results suggest an association between a single gene and pair-bonding behavior in humans, and indicate that the well characterized influence of AVP on pair-bonding in voles may be of relevance also for humans.
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| 8. |
- Walum, Hasse, et al.
(författare)
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Variation in the oxytocin receptor gene is associated with pair-bonding and social behavior
- 2012
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Ingår i: Biological Psychiatry. - New York, USA : Elsevier. - 0006-3223 .- 1873-2402. ; 71:5, s. 419-426
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Tidskriftsartikel (refereegranskat)abstract
- Background: In specific vole and primate species the neuropeptide oxytocin plays a central role in the regulation of pair-bonding behavior. Here we investigate the extent to which genetic variants in the oxytocin receptor gene (OXTR) are associated with pair-bonding and related social behaviors in humans.Methods: We first genotyped twelve single nucleotide polymorphisms (SNPs) in the TOSS (Twin and Offspring Study in Sweden) (n = 2309) and the TCHAD (Swedish Twin Study of Child and Adolescent Development) (n = 1240), comprising measures of self-reported pair-bonding behavior. In the TOSS sample we further investigated one of the SNPs for measures of marital status and quality. Moreover, in the TCHAD sample we explored the longitudinal relationship between precursors of pair-bonding during childhood and subsequent behavior in romantic relationships. Finally, in the TCHAD study and in the Child and Adolescent Twin Study of Sweden (CATSS) (n = 1771), the association between the same SNP and childhood behaviors was investigated.Results: One SNP (rs7632287) in OXTR was associated with traits reflecting pair-bonding in women in the TOSS and TCHAD samples. In girls the rs7632287 SNP was further associated with childhood social problems, which longitudinally predicted pair-bonding behavior in the TCHAD sample. This association was replicated in the CATSS sample in which an association between the same SNP and social interaction deficit symptoms from the autism spectrum was detected.Conclusion: These results suggest an association between variation in OXTR and human pair-bonding and other social behaviors, possibly indicating that the well-described influence of oxytocin on affiliative behavior in voles could also be of importance for humans.
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| 9. |
- Zettergren, Anna, 1978, et al.
(författare)
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Associations between polymorphisms in sex steroid related genes and autistic-like traits.
- 2013
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 1873-3360 .- 0306-4530. ; 38:11
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Tidskriftsartikel (refereegranskat)abstract
- Sex differences in psychiatric disorders are common, which is particularly striking in autism spectrum disorders (ASDs) that are four times more prevalent in boys. High levels of testosterone during early development have been hypothesized to be a risk factor for ASDs, supported by several studies showing fetal testosterone levels, as well as indirect measures of prenatal androgenization, to be associated with ASDs and autistic-like traits (ALTs). Further, the importance of sex steroid related genes in ASDs is supported by studies reporting associations between polymorphisms in genes involved in sex steroid synthesis/metabolism and ASDs and ALTs. The aim of the present study was to investigate possible associations between 29 single nucleotide polymorphisms (SNPs) in eight genes related to sex steroids and autistic features. Individuals included in the study belong to a subset (n=1771) from The Child and Adolescent Twin Study in Sweden (CATSS), which are all assessed for ALTs. For two SNPs, rs2747648 located in the 3'-UTR of ESR1 encoding the estrogen receptor alpha and rs523349 (Leu89Val) located in SRD5A2 encoding 5-alpha-reductase, type 2, highly significant associations with ALTs were found in boys and girls, respectively. The results of the present study suggest that SNPs in sex steroid related genes, known to affect gene expression (rs2747648 in ESR1) and enzymatic activity (Leu89Val in SRD5A2), seem to be associated with ALTs in a general population. In conclusion, the current findings provide further support for a role of sex steroids in the pathophysiology of ASDs.
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| 10. |
- Zettergren, Anna, 1978, et al.
(författare)
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Further investigations of the relation between polymorphisms in sex steroid related genes and autistic-like traits.
- 2016
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Ingår i: Psychoneuroendocrinology. - Stockholm : Elsevier BV. - 1873-3360 .- 0306-4530. ; 68, s. 1-5
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Tidskriftsartikel (refereegranskat)abstract
- Autism spectrum disorders (ASDs) are more prevalent in boys than in girls, indicating that high levels of testosterone during early development may be a risk factor. Evidence for this hypothesis comes from studies showing associations between fetal testosterone levels, as well as indirect measures of prenatal androgenization, and ASDs and autistic-like traits (ALTs). In a recent study we reported associations between ALTs and single nucleotide polymorphisms (SNPs) in the genes encoding estrogen receptor 1 (ESR1), steroid-5-alpha-reductase, type 2 (SRD5A2) and sex hormone-binding globulin (SHBG) in a subset (n=1771) from the Child and Adolescent Twin Study in Sweden (CATSS). The aim of the present study was to try to replicate these findings in an additional, larger, sample of individuals from the CATSS (n=10,654), as well as to analyze additional SNPs of functional importance in SHBG and SRD5A2. No associations between the previously associated SNPs in the genes ESR1 and SRD5A2 and ALTs could be seen in the large replication sample. Still, our results show that two non-linked SNPs (rs6259 and rs9901675) at the SHBG gene locus might be of importance for language impairment problems in boys. The results of the present study do not point toward a major role for the investigated SNPs in the genes ESR1 and SRD5A2 in ALTs, but a possible influence of genetic variation in SHBG, especially for language impairment problems in boys, cannot be ruled out.
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