Dataset Information

Association of COMT (Val158Met) and BDNF (Val66Met) gene polymorphisms with anxiety, ADHD and tics in children with autism spectrum disorder.

ABSTRACT: The aim of the study is to examine rs4680 (COMT) and rs6265 (BDNF) as genetic markers of anxiety, ADHD, and tics. Parents and teachers completed a DSM-IV-referenced rating scale for a total sample of 67 children with autism spectrum disorder (ASD). Both COMT (p = 0.06) and BDNF (p = 0.07) genotypes were marginally significant for teacher ratings of social phobia (etap (2) = 0.06). Analyses also indicated associations of BDNF genotype with parent-rated ADHD (p = 0.01, etap (2) = 0.10) and teacher-rated tics (p = 0.04; etap (2) = 0.07). There was also evidence of a possible interaction (p = 0.02, etap (2) = 0.09) of BDNF genotype with DAT1 3' VNTR with tic severity. BDNF and COMT may be biomarkers for phenotypic variation in ASD, but these preliminary findings remain tentative pending replication with larger, independent samples.

SUBMITTER: Gadow KD

PROVIDER: S-EPMC4348067 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature

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Association of COMT (Val158Met) and BDNF (Val66Met) gene polymorphisms with anxiety, ADHD and tics in children with autism spectrum disorder.

Gadow Kenneth D KD Roohi Jasmin J DeVincent Carla J CJ Kirsch Sarah S Hatchwell Eli E

Journal of autism and developmental disorders 20090707 11

The aim of the study is to examine rs4680 (COMT) and rs6265 (BDNF) as genetic markers of anxiety, ADHD, and tics. Parents and teachers completed a DSM-IV-referenced rating scale for a total sample of 67 children with autism spectrum disorder (ASD). Both COMT (p = 0.06) and BDNF (p = 0.07) genotypes were marginally significant for teacher ratings of social phobia (etap (2) = 0.06). Analyses also indicated associations of BDNF genotype with parent-rated ADHD (p = 0.01, etap (2) = 0.10) and teacher ...[more]

PMID: 19582565

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Project description:Emotional distress is a common, but poorly addressed, feature of moderate-severe traumatic brain injury (TBI). Previously identified sociodemographic, psychological, and injury-related factors account for only a small proportion of the variability in emotional distress post-TBI. Genetic factors may help to further understand emotional distress in this population. The catechol-O-methyltransferase (COMT) Val158 and brain-derived neurotrophic factor (BDNF) 66Met single-nucleotide polymorphisms (SNPs) have been identified as possible contributory factors to outcomes after TBI. We investigated whether the COMT Val158 and BDNF 66Met SNPs were associated with emotional distress 1 year after moderate-severe TBI, and whether these associations were moderated by age, sex, and TBI severity (as measured by the duration of post-traumatic amnesia [PTA]). Moderate-severe TBI survivors (COMT, n = 391; BDNF, n = 311) provided saliva samples after admission to a TBI rehabilitation hospital. At a follow-up interview ∼1 year after injury, participants completed a self-report measure of emotional distress (Hospital Anxiety and Depression Scale; HADS). Multiple linear regression models were constructed for each SNP to predict total scores on the HADS. Neither COMT Val158 nor BDNF 66Met carriage status (carrier vs. non-carrier) significantly predicted emotional distress (COMT, p = 0.49; BDNF, p = 0.66). Interactions of SNP × age (COMT, p = 0.90; BDNF, p = 0.93), SNP × sex (COMT, p = 0.09; BDNF, p = 0.60), SNP × injury severity (COMT, p = 0.53; BDNF, p = 0.87), and SNP × sex × age (COMT, p = 0.08; BDNF, p = 0.76) were also non-significant. Our null findings suggest that COMT Val158 and BDNF 66Met SNPs do not aid the prediction of emotional distress 1 year after moderate-severe TBI, neither in isolation nor in interaction with age, sex and injury severity. The reporting of null findings such as ours is important to avoid publication bias and prompt researchers to consider the challenges of single-gene candidate studies in understanding post-TBI outcomes. Analyses in larger samples that incorporate multiple genetic factors and their relevant moderating factors may provide a greater understanding of the role of genetics in post-TBI emotional distress.

Project description:Math anxiety (MA) is a phobic reaction to math activities, potentially impairing math achievement. Higher frequency of MA in females is explainable by the interaction between genetic and environmental factors. The molecular-genetic basis of MA has not been investigated. The COMT Val158Met polymorphism, which affects dopamine levels in the prefrontal cortex, has been associated with anxiety manifestations. The valine allele is associated with lower, and the methionine allele with higher, dopamine availability. In the present study, the effects of sex and COMT Val158Met genotypes on MA were investigated: 389 school children aged 7-12 years were assessed for intelligence, numerical estimation, arithmetic achievement and MA and genotyped for COMT Val158Met polymorphism. The Math Anxiety Questionnaire (MAQ) was used to assess the cognitive and affective components of MA. All genotype groups of boys and girls were comparable regarding genotype frequency, age, school grade, numerical estimation, and arithmetic abilities. We compared the results of all possible genetic models: codominance (Val/Val vs. Val/Met vs. Met/Met), heterosis (Val/Met vs. Val/Val plus Met/Met), valine dominance (Val/Val plus Val/Met vs. Met/Met), and methionine dominance (Met/Met plus Val/Met vs. Val/Val). Models were compared using AIC and AIC weights. No significant differences between girls and boys and no effects of the COMT Val158Met polymorphism on numerical estimation and arithmetic achievement were observed. Sex by genotype effects were significant for intelligence and MA. Intelligence scores were higher in Met/Met girls than in girls with at least one valine allele (valine dominance model). The best fitting model for MA was heterosis. In Anxiety Toward Mathematics, heterozygous individuals presented MA levels close to the grand average regardless of sex. Homozygous boys were significantly less and homozygous girls significantly more math anxious. Heterosis has been seldom explored, but in recent years has emerged as the best genetic model for some phenotypes associated with the COMT Val158Met polymorphism. This is the first study to investigate the genetic-molecular basis of MA.

Project description:ObjectiveAdolescence is a developmental stage in which the incidence of psychiatric disorders, such as anxiety disorders, peaks. Selective serotonin reuptake inhibitors (SSRIs) are the main class of agents used to treat anxiety disorders. However, the impact of SSRIs on the developing brain during adolescence remains unknown. The authors assessed the impact of developmentally timed SSRI administration in a genetic mouse model displaying elevated anxiety-like behaviors.MethodKnock-in mice containing a common human single-nucleotide polymorphism (Val66Met; rs6265) in brain-derived neurotrophic factor (BDNF), a growth factor implicated in the mechanism of action of SSRIs, were studied based on their established phenotype of increased anxiety-like behavior. Timed administration of fluoxetine was delivered during one of three developmental periods (postnatal days 21-42, 40-61, or 60-81), spanning the transition from childhood to adulthood. Neurochemical and anxiety-like behavioral analyses were performed.ResultsWe identified a "sensitive period" during periadolescence (postnatal days 21-42) in which developmentally timed fluoxetine administration rescued anxiety-like phenotypes in BDNF Val66Met mice in adulthood. Compared with littermate controls, BDNFMet/Met mice exhibited diminished maturation of serotonergic fibers projecting particularly to the prefrontal cortex, as well as decreased expression of the serotonergic trophic factor S100B in the dorsal raphe. Interestingly, deficient serotonergic innervation, as well as S100B levels, were rescued with fluoxetine administration during periadolescence.ConclusionsThese findings suggest that SSRI administration during a "sensitive period" during periadolescence leads to long-lasting anxiolytic effects in a genetic mouse model of elevated anxiety-like behaviors. These persistent effects highlight the role of BDNF in the maturation of the serotonin system and the capacity to enhance its development through a pharmacological intervention.

Dataset Information

Association of COMT (Val158Met) and BDNF (Val66Met) gene polymorphisms with anxiety, ADHD and tics in children with autism spectrum disorder.

Publications

Association of COMT (Val158Met) and BDNF (Val66Met) gene polymorphisms with anxiety, ADHD and tics in children with autism spectrum disorder.

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