Elsevier

Biological Psychiatry

Volume 70, Issue 3, 1 August 2011, Pages 216-221
Biological Psychiatry

Archival Report
Catechol-O-Methyltransferase Valine158Methionine Polymorphism Moderates Methylphenidate Effects on Oppositional Symptoms in Boys with Attention-Deficit/Hyperactivity Disorder

https://doi.org/10.1016/j.biopsych.2011.03.025Get rights and content

Background

The catechol-O-methyltransferase enzyme plays a key role in the function of prefrontal cortex, accounting for most of the degradation of dopamine. Previous studies have documented the improvement of oppositional symptoms in attention-deficit/hyperactivity disorder (ADHD) patients with methylphenidate (MPH) treatment. However, the effect of the COMT gene in the response to MPH on oppositional symptoms has not been investigated.

Methods

A total of 251 children with ADHD fulfilled inclusion criteria to participate in the study. Dosages of short-acting MPH were augmented until no further clinical improvement was detected or until there were significant adverse events (MPH dose always > .3 mg/kg/day). The outcome measure was the parent-rated oppositional subscale of the Swanson, Nolan and Pelham Scale-Version IV (SNAP-IV). The scale was applied by child psychiatrists blinded to genotype at baseline and in the first and third months. The COMT valine158methionine polymorphism was genotyped by polymerase chain reaction based methods.

Results

We detected significant improvement in SNAP-IV oppositional scores from baseline to the first and three months of treatment [n = 112; F(2,231) = 5.35, p = .005]. A significant effect of the presence of methionine allele in oppositional defiant disorder scores during treatment [F(1,148) = 5.02, p = .027] and a significant interaction between the methionine allele and treatment over time for the SNAP-IV oppositional scores during this period of treatment [F(2,229) = 6.40, p = .002] were both observed.

Conclusions

These results suggest an effect of the COMT genotype on the trajectory of oppositional defiant disorder symptoms improvement with MPH treatment in boys with ADHD.

Section snippets

Subjects

The sample for this investigation included children and adolescents who were consecutively evaluated for 2 years in the ADHD Outpatient Clinic at the Hospital de Clínicas de Porto Alegre. Inclusion criteria for this investigation were ADHD diagnosis according to DSM-IV criteria, age between 4 and 17 years, European-Brazilian ethnicity as determined by skin color and morphological characteristics, drug-naive for MPH, and prescribed MPH doses of at least .3 mg/kg/day. The diagnoses of ADHD and

Results

The allele frequencies observed were .56 and .44 for Val and Met alleles, respectively. The genotype distributions were consistent with Hardy-Weinberg equilibrium. About 32% of individuals were Val/Val homozygous, 50% were heterozygous, and 18% were Met/Met homozygous.

Table 1 shows demographic and clinical characteristics of patients according to the presence of the Met allele. Genotype/alleles were coded a priori based on functional activity and association with risk of aggressive/antisocial

Discussion

This investigation suggested that ADHD boys with at least one Met allele have a significantly different trajectory of improvement on oppositional symptoms than Val homozygotes when they are treated with MPH. We are unaware of any previous studies investigating the effect of COMT gene specifically in oppositional symptoms in response to methylphenidate treatment.

Although the biological mechanisms to explain our results have not yet been fully determined, we can consider some important points.

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