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An association between ADRA2A -1291 C > G polymorphism and response to methylphenidate in inattentive symptoms was previously suggested in children with ADHD. No investigation specifically assessed this association in ADHD-inattentive type (ADHD-I). In this naturalistic pharmacogenetic study, 59 subjects with ADHD-I from a non-referred sample were treated with short-acting methylphenidate and genotyped for ADRA2A -1291 C > G polymorphism. The primary outcome measure was the inattentive subscale of the SNAP-IV applied by a child psychiatrist blinded to genotype at baseline and first month of treatment. Children and adolescents with the G allele showed significantly lower inattentive scores with MPH treatment at the first month of treatment than subjects without the G allele (n = 59; F = 6.14; p = 0.016). We extended to ADHD-I previous findings suggesting the influence of the G allele at the ADRA2A -1291 C > G polymorphism on the improvement of inattentive symptoms with methylphenidate in children with all ADHD subtypes.

Latrophilin 3 ( LPHN3) is a brain-specific member of the G-protein coupled receptor family associated to both attention-deficit/hyperactivity disorder ( ADHD) genetic susceptibility and methylphenidate ( MPH) pharmacogenetics. Interactions of LPHN3 variants with variants harbored in the 11q chromosome improve the prediction of ADHD development and medication response. The aim of this study was to evaluate the role of LPHN3 variants in childhood ADHD susceptibility and treatment response in a naturalistic clinical cohort. The association between LPHN3 and ADHD was evaluated in 523 children and adolescents with ADHD and 132 controls. In the pharmacogenetic study, 172 children with ADHD were investigated. The primary outcome measure was the parent-rated Swanson, Nolan and Pelham Scale - version IV applied at baseline, first and third months of treatment with MPH. The results reported herein suggest the CGC haplotype derived from single nucleotide polymorphisms ( SNPs) rs6813183, rs1355368 and rs734644 as an ADHD risk haplotype ( P = 0.02, OR = 1.46). Although non-significant after multiple testing correction, its interaction with the 11q chromosome SNP rs965560 slightly increases risk ( P = 0.03, OR = 1.55). Homozygous individuals for the CGC haplotype showed faster response to MPH treatment as a significant interaction effect between CGC haplotype and treatment over time was observed ( P < 0.001). Homozygous individuals for the GT haplotype derived from SNPs rs6551665 and rs1947275 showed a nominally significant interaction with treatment over time ( P = 0.04). Our findings replicate previous findings reporting that LPHN3 confers ADHD susceptibility, and moderates MPH treatment response in children and adolescents with ADHD. [ABSTRACT FROM AUTHOR]

An association between ADRA2A −1291 C > G polymorphism and response to methylphenidate in inattentive symptoms was previously suggested in children with ADHD. No investigation specifically assessed this association in ADHD–inattentive type (ADHD-I). In this naturalistic pharmacogenetic study, 59 subjects with ADHD-I from a non-referred sample were treated with short-acting methylphenidate and genotyped for ADRA2A −1291 C > G polymorphism. The primary outcome measure was the inattentive subscale of the SNAP-IV applied by a child psychiatrist blinded to genotype at baseline and first month of treatment. Children and adolescents with the G allele showed significantly lower inattentive scores with MPH treatment at the first month of treatment than subjects without the G allele ( n = 59; F = 6.14; p = 0.016). We extended to ADHD-I previous findings suggesting the influence of the G allele at the ADRA2A −1291 C > G polymorphism on the improvement of inattentive symptoms with methylphenidate in children with all ADHD subtypes. [ABSTRACT FROM AUTHOR]