Pharmacogenetics of methylphenidate response in preschoolers with ADHD
James McGOUGH1, James McCRACKEN2, James Swanson2
1Drs. McGough and McCracken and Ms. Shigawa are with the UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles; Drs. Swanson, T. Wigal, and S. Wigal are with the University of California, Irvine; Drs. Greenhill and Posner, Mr. Davies (retired), Ms. Chuang, and Ms. Skrobala are with New York State Psychiatric Institute, Columbia University, New York; Drs. Riddle and Kastelic are with Johns Hopkins University, Baltimore; Dr. Kollins is with Duke University Medical Center, Durham, NC; Dr. Abikoff is with the New York University Child Study Center, New York; Dr. Ghuman is with the University of Arizona, Tucson; Dr. Cunningham is with the McMaster University, Hamilton, Ontario, Canada; Dr. Moyzis is with the University of California, Irvine; and Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD..
Objective:
The authors explored genetic moderators of symptom reduction and side effects in methylphenidate-treated preschool-age children diagnosed with attention-deficit/hyperactivity disorder (ADHD).
Method:
DNA was isolated from 81 subjects in a double-blind, placebo-controlled, crossover methylphenidate titration. Parents and teachers completed ADHD symptom scales and side effect ratings for each of five randomly administered weekly conditions that included immediate-release methylphenidate 1.25, 2.5, 5.0, 7.5 mg and placebo given three times daily. Candidate genes hypothesized to influence stimulant effects or individual risks for ADHD were genotyped.
Results:
Although the primary analysis did not indicate significant genetic effects, secondary analyses revealed associations between symptom response and variants at the dopamine receptor (DRD4) promoter (p=.05) and synaptosomal-associated protein 25 (SNAP25) allelesT1065G (p=.03) andT1069C (p=.05). SNAP25 variants were also associated with tics (p=.02), buccal-lingual movements (p=.01), and irritability (p=04). DRD4 variants were also associated with picking (p=.03). Increasing dose predicted irritability (p=.05) and social withdrawal (p=.03) with DRD4 variants. There were no significant effects for the dopamine transporter (DAT1).
Conclusions:
Emerging evidence suggests the potential for understanding the individual variability of response to and side effects of ADHD medications from the study of genetics, although additional research is required before these findings are proven to have clinical utility.
More Related Videos
05:48The Adventures of Fundi Intervention Based on the Cognitive and Emotional Processing in Attention Deficit Hyperactive Disorder Patients
Published on: June 12, 2020
13:35A Convenient Method for Extraction and Analysis with High-Pressure Liquid Chromatography of Catecholamine Neurotransmitters and Their Metabolites
Published on: March 1, 2018
Related Concept Videos
Attention-Deficit/Hyperactivity Disorder
Diagnostic Criteria and Symptoms
To diagnose ADHD, symptoms must manifest before age 12 and be evident across multiple settings.
Pharmacokinetics in Pediatric Patients: Drug Metabolism
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
Pharmacogenetics of Drug Metabolism: Overview
Pharmacogenetics and Pharmacogenomics: Overview
Human Genetics
The complex relationship between genetics and psychology is observable through common biological components such...
