Association study of the brain‐derived neurotropic factor (BDNF) gene in attention deficit hyperactivity disorder

Cummins

Int. J. Neuropsychopharm.

et al. 2011

Research on psychostimulants, analysis of animal models and genetic association studies all suggest that the brain-derived neurotrophic factor gene (BDNF) may be a good candidate for pharmacogenetic studies of attention deficit hyperactivity disorder (ADHD). Yet to date there have been no pharmacogenetic studies of BDNF in ADHD. A total of 102 drug-naive ADHD children (8.7±2.1 yr) were treated with osmotic release oral system-methylphenidate (OROS-MPH) for 12 wk, and four kinds of response criteria were applied, based first, on a combined threshold of the ADHD Rating Scale - IV (ARS) and the Clinical Global Impression - Improvement scale (CGI-I); second, on scores of 1 or 2 vs. 3-7 on the CGI - Severity scale; third, on a >50% reduction in ARS scores; and fourth, on satisfaction of all of the aforementioned criteria. The Val⁶⁶Met polymorphism of BDNF and six single nucleotide polymorphisms from the SLC6A2, ADRA2A and NTF-3 genes were tested for association with each criterion. Relative to other genotypes, homozygosity for the Val allele of the BDNF Val⁶⁶Met polymorphism was associated with a greater relative frequency of good response under all four response criteria (after controlling for baseline ARS score, age, gender, final dose (mg/kg) of OROS-MPH at 12 wk, and level of academic functioning). This association was significant at the uncorrected level for the first and third response criteria (p=0.013 and p=0.018, respectively) and significant at a Bonferroni-corrected level for the second and fourth response criteria (p=0.0002, p=0.0003, respectively). Our findings support an association between homozygosity for the Val allele of BDNF and better response to OROS-MPH in Korean ADHD children as assessed by four different response criteria.

Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Val/Val genotype of brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is associated with a better response to OROS-MPH in Korean ADHD children

Cummins

Int. J. Neuropsychopharm.

et al. 2011

“…37 Moreover, the present BDNF SNP (rs2049046) has also been used to investigate whether its allelic variants were associated with several mental health outcomes, such as attention deficit hyperactivity disorder, autism, obsessivecompulsive disorder and migraine. [40][41][42] PON1 codes for an enzyme that inhibits oxidation of lipoproteins through hydrolysis of lipid peroxides. Such oxidative damage can be induced by methylmercury.…”

Section: Discussionmentioning

confidence: 99%

Prenatal Methylmercury Exposure and Genetic Predisposition to Cognitive Deficit at Age 8 Years

et al. 2013

Background: Cognitive consequences at school age associated with prenatal methylmercury exposure may need to take into account nutritional and socio-demographic cofactors as well as relevant genetic polymorphisms. Methods: A sub-sample (n = 1311) of the Avon Longitudinal Study of Parents And Children (Bristol, UK) was selected and mercury concentrations were measured in freeze-dried umbilical cord tissue as a measure of methylmercury exposure. A total of 1135 children had available data on 247 single-nucleotide polymorphisms (SNPs) within relevant genes, as well as the Wechsler Intelligence Scale for Children Intelligence Quotient (IQ) scores at age 8 years. Multivariate regression models were used to assess the associations between methylmercury exposure and IQ and to determine possible gene-environment interactions. Results: Mercury concentrations indicated low background exposures (mean = 26 ng/g, standard deviation = 13). Log-10-transformed mercury was positively associated with IQ, which attenuated after adjustment for nutritional and socio-demographic cofactors. In stratified analyses, a reverse association was found in higher social class families (p-value for interaction = 0.0013, performance IQ), among whom there was a wider range of methylmercury exposure. Among 40 SNPs showing nominally significant main effects, methylmercury interactions were detected for rs662 (Paraoxonase 1) and rs1042838 (Progesterone Receptor) (p < 0.05) and for rs3811647 (Transferrin) and rs2049046 (Brain-Derived Neurotrophic Factor) (p < 0.10). Conclusions: In this population with a low level of methylmercury exposure, there were only equivocal associations between methylmercury exposure and adverse neuropsychological outcomes. Heterogeneities in several relevant genes suggest possible genetic predisposition to methylmercury neurotoxicity in a substantial proportion of the population. Future studies need to address this possibility.

“…Four TDT (Brookes et al 2006a;Kent et al 2005;Lee et al 2007;Schimmelmann et al 2007) and four Case-Control/HHRR Guan et al 2008;Xu et al 2007b) studies were identiWed for meta-analysis that tested for association between this Val66Met polymorphism and ADHD. Based on previous research (Egan et al 2003;Kent et al 2005), the 'G' or Valine allele was designated as the 'risk' allele.…”

Section: Brain Derived Neurotrophic Factor Gene (Bdnf)mentioning

confidence: 99%

Candidate gene studies of ADHD: a meta-analytic review

2009

Quantitative genetic studies (i.e., twin and adoption studies) suggest that genetic influences contribute substantially to the development of attention deficit hyperactivity disorder (ADHD). Over the past 15 years, considerable efforts have been made to identify genes involved in the etiology of this disorder resulting in a large and often conflicting literature of candidate gene associations for ADHD. The first aim of the present study was to conduct a comprehensive meta-analytic review of this literature to determine which candidate genes show consistent evidence of association with childhood ADHD across studies. The second aim was to test for heterogeneity across studies in the effect sizes for each candidate gene as its presence might suggest moderating variables that could explain inconsistent results. Significant associations were identified for several candidate genes including DAT1, DRD4, DRD5, 5HTT, HTR1B, and SNAP25. Further, significant heterogeneity was observed for the associations between ADHD and DAT1, DRD4, DRD5, DBH, ADRA2A, 5HTT, TPH2, MAOA, and SNAP25, suggesting that future studies should explore potential moderators of these associations (e.g., ADHD subtype diagnoses, gender, exposure to environmental risk factors). We conclude with a discussion of these findings in relation to emerging themes relevant to future studies of the genetics of ADHD.