Molecular imaging genetics of methylphenidate response in ADHD and substance use comorbidity

Purpose: Attention‐deficit/hyperactivity disorder (ADHD) and substance use disorders (SUDs) are highly comorbid and may share a genetic vulnerability. Methylphenidate (MPH), a dopamine transporter (DAT) blocker, is an effective drug for most ADHD patients. Although dopamine D4 receptor (DRD4) and do...

Full description

Saved in:
Bibliographic Details
Published in:Synapse (New York, N.Y.) N.Y.), 2011-02, Vol.65 (2), p.154-159
Main Authors: Szobot, Claudia M., Roman, Tatiana, Hutz, Mara H., Genro, Júlia P., Shih, Ming Chi, Hoexter, Marcelo Q., Júnior, Neivo, Pechansky, Flávio, Bressan, Rodrigo A., Rohde, Luis A.P.
Format: Article
Language:English
Subjects:
Adolescence
Adolescent
Attention Deficit Disorder with Hyperactivity - diagnostic imaging
Attention Deficit Disorder with Hyperactivity - drug therapy
Attention Deficit Disorder with Hyperactivity - epidemiology
Attention Deficit Disorder with Hyperactivity - genetics
Attention deficit hyperactivity disorder
Brain
Brain - diagnostic imaging
Brain - drug effects
Brain - pathology
Brain Mapping
Clinical trials
Comorbidity
Computed tomography
DAT1
Dopamine D4 receptors
Dopamine Plasma Membrane Transport Proteins - genetics
Dopamine transporter
Dopamine Uptake Inhibitors - pharmacology
Dopamine Uptake Inhibitors - therapeutic use
DRD4
Drug Administration Schedule
Drug Delivery Systems
Drugs
Gene Frequency
Genotype
Genotypes
Humans
Linear Models
Male
Methylphenidate
Methylphenidate - pharmacology
Methylphenidate - therapeutic use
Neostriatum
Neuroimaging
Organotechnetium Compounds - pharmacokinetics
Putamen
Radiopharmaceuticals - pharmacokinetics
Receptors, Dopamine D4 - genetics
Single photon emission computed tomography
SPECT
substance use disorders
Substance-Related Disorders - diagnostic imaging
Substance-Related Disorders - drug therapy
Substance-Related Disorders - epidemiology
Substance-Related Disorders - genetics
Synapses
Tomography, Emission-Computed, Single-Photon - methods
Tropanes - pharmacokinetics
Young Adult
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Purpose: Attention‐deficit/hyperactivity disorder (ADHD) and substance use disorders (SUDs) are highly comorbid and may share a genetic vulnerability. Methylphenidate (MPH), a dopamine transporter (DAT) blocker, is an effective drug for most ADHD patients. Although dopamine D4 receptor (DRD4) and dopamine transporter (DAT1) genes have a role in both disorders, little is known about how these genes influence brain response to MPH in individuals with ADHD/SUDs. The goal of this study was to evaluate whether ADHD risk alleles at DRD4 and DAT1 genes could predict the change in striatal DAT occupancy after treatment with MPH in adolescents with ADHD/SUDs. Methods: Seventeen adolescents with ADHD/SUDs underwent a SPECT scan with [Tc99m]TRODAT‐1 at baseline and after three weeks on MPH. Caudate and putamen DAT binding potential was calculated. Comparisons on DAT changes were made according to the subjects' genotype. Results: The combination of both DRD4 7‐repeat allele (7R) and homozygosity for the DAT1 10‐repeat allele (10/10) was significantly associated with a reduced DAT change after MPH treatment in right and left caudate and putamen, even adjusting the results for potential confounders (P ≤ 0.02; R2 from 0.50 to 0.56). Conclusions: In patients with ADHD/SUDs, combined DRD4 7R and DAT1 10/10 could index MPH reduced DAT occupancy. This might be important for clinical trials, in terms of better understanding individual variability in treatment response. Synapse 2011. © 2010 Wiley‐Liss, Inc.
ISSN:0887-4476
1098-2396
1098-2396
DOI:10.1002/syn.20829