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Integrative genomic analysis of methylphenidate response in attention-deficit/hyperactivity disorder.

ABSTRACT: Methylphenidate (MPH) is the most frequently used pharmacological treatment in children with attention-deficit/hyperactivity disorder (ADHD). However, a considerable interindividual variability exists in clinical outcome. Thus, we performed a genome-wide association study of MPH efficacy in 173 ADHD paediatric patients. Although no variant reached genome-wide significance, the set of genes containing single-nucleotide polymorphisms (SNPs) nominally associated with MPH response (P?

SUBMITTER: Pagerols M

PROVIDER: S-EPMC5789875 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Integrative genomic analysis of methylphenidate response in attention-deficit/hyperactivity disorder.

Pagerols Mireia M Richarte Vanesa V Sánchez-Mora Cristina C Rovira Paula P Soler Artigas María M Garcia-Martínez Iris I Calvo-Sánchez Eva E Corrales Montse M da Silva Bruna Santos BS Mota Nina Roth NR Victor Marcelo Moraes MM Rohde Luis Augusto LA Grevet Eugenio Horacio EH Bau Claiton Henrique Dotto CHD Cormand Bru B Casas Miguel M Ramos-Quiroga Josep Antoni JA Ribasés Marta M

Scientific reports 20180130 1

Methylphenidate (MPH) is the most frequently used pharmacological treatment in children with attention-deficit/hyperactivity disorder (ADHD). However, a considerable interindividual variability exists in clinical outcome. Thus, we performed a genome-wide association study of MPH efficacy in 173 ADHD paediatric patients. Although no variant reached genome-wide significance, the set of genes containing single-nucleotide polymorphisms (SNPs) nominally associated with MPH response (P < 0.05) was sig ...[more]

PMID: 29382897

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Effect of methylphenidate on gene expression profiles of Attention Deficit Hyperactivity Disorder patients and unaffected controls.

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Methylphenidate normalizes frontocingulate underactivation during error processing in attention-deficit/hyperactivity disorder.

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Project description:Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in which a significant proportion of patients do not respond to treatment. The objective of this study was to examine the role of genetic risk variants in the response to treatment with methylphenidate (MPH). The effectiveness of MPH was evaluated based on variations in the CGI-S and CGAS scales over a 12-month treatment period using linear mixed effects models. A total of 208 ADHD patients and 34 polymorphisms were included in the analysis. For both scales, the response was associated with time, extended-release MPH/both formulations, and previous MPH treatment. For the CGI-S scale, response was associated with SLC6A3 rs2550948, DRD4 promoter duplication, SNAP25 rs3746544, and ADGRL3 rs1868790. Interactions between the response over time and SLC6A3 and DRD2 were found in the CGI-S and CGAS scales, respectively. The proportion of the variance explained by the models was 18% for the CGI-S and 22% for the CGAS. In this long-term study, the effects of SLC6A3, DRD4, SNAP25, and ADGRL3 on response to treatment reflect those observed in previous studies. In addition, 2 previously unreported interactions with response to treatment over a 12-month period were found (SLC6A3 and DRD2).

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Individualizing the dosage of Methylphenidate in children with attention deficit hyperactivity disorder.

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