Association between tryptophan hydroxylase 2, performance on a continuance performance test and response to methylphenidate in ADHD participants

American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics
I ManorR Ebstein

Abstract

The main objective of this study was to examine neuropsychological mechanisms mediating the association between tryptophan hydroxylase 2 (TPH2) and attention deficit hyperactivity disorder (ADHD). A continuous performance test (T.O.V.A.) was administered to 344 participants diagnosed with DSM IV ADHD who were also genotyped for eight TPH2 intronic SNPs. Association between TPH2 (single SNPs and haplotypes), ADHD, and performance on the T.O.V.A. were tested using robust family-based association tests as implemented in two statistical genetic programs: UNPHASED and PBAT. Association was only observed between an eight locus haplotype and ADHD DSM IV combined type III (global P = 0.036). Robust association was observed between TPH2 single SNPs (and haplotypes) and performance on the T.O.V.A., especially Errors of Omission (eight locus haplotypes, global P = 0.038). Significant associations were also observed between TPH2 and improvement (before-after scores) in T.O.V.A. Total Response Variability scores following acute methylphenidate challenge (eight locus haplotypes, global P = 0.009). Using the MFBAT program, significant multivariate association was observed between single SNPs and haplotypes [eight locus haplotypes and all four...Continue Reading

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