| Summary |
Objective:This study ascertained the association between attention deficit/hyperactivity disorder (ADHD) in Japanese children and a polymorphism of catechol-O-methyltransferase (COMT),a dopamine-control gene. The secondary aim of the study was the evaluation of a putative association between methylphenidate (MPH) effect/adverse effects and the COMT genotype. Methods: To ascertain the distribution of the Val158Met variant of COMT, 50 children meeting ADHD inclusion criteria were compared with 32 healthy children. Clinical improvement and the occurrence of adverse effects were measured before and 3months after MPH administration in children with ADHD,and analyzed for genotype association. Wechsler Intelligence Scale for Children-Third Edition (WISC-III),age,MPH dose were included as co-variables. Results: The occurrence of the COMT Val/Val genotype was significantly higher in children with ADHD (chi2(1)=7.13, p<0.01). However, there was no significant difference in the Val/Val genotype according to disorder, and WISC and ADHD rating scale scores, after correcting for the interaction between disorder and COMT genotype. Furthermore, no significant difference in MPH effect/adverse effects was observed in association with the COMT genotype in the ADHD group. Conclusions: These results showed a lack of association between the COMT Val/Val genotype and ADHD in Japan. |
| Total Sample |
50 males children in case sample; 32 males children in control sample |
| Sample Collection |
Fifty male children of ages 6-16 years who met the Diagnostic and Statistical Manual of Mental Disorders DSM-IV Text Revision£¨DSM-IV-TR) criteria of ADHD were recruited from the child psychiatry outpatient clinic at Kumamoto University in Japan. For comparison, 32 healthy schoolchildren of the same age range were recruited from the community. Exclusion criteria for both healthy and ADHD children were; lifetime diagnosis of any psychiatric disorder, head trauma with loss of consciousness, lifetime substance abuse, any history of epilepsy, significant fetal exposure to alcohol or drugs, and perinatal complications. Females were also excluded from the study. No participants had any medication with psychopharmacological components prior this study. ADHD patients were administered 18 or 27 mg of OROS-MPH (0.5-1.2 mg/kg per day), depending on age and body weight. No placebo was given to either ADHD patients or healthy adolescents. |
| Diagnosis Description |
the Diagnostic and Statistical Manual of Mental Disorders DSM-IV Text Revision (DSM-IV-TR) criteria; for symptom severity of ADHD, and the Wechsler Intelligence Scale for Children-Third Edition (WISC-III). To exclude other psychiatric diagnoses, the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) was also administered. For comparison, 32 healthy schoolchildren of the same age range were recruited from the community, and WISC, ADHDRS,SDS evaluation was done. |
| Technique |
For genotyping, COMT Val108/158Met polymorphism was genotyped using polymerase chain reactionbased methods, both primer and probe using genotyping assays (Taqman? SNP; Applied Biosystems, LIFE Technologies Japan; Tokyo, Japan) and sequence detection systems (ABI Prism? 7900HT; Applied Biosystems) with protocols described previously. All children were examined the COMT genotype, divided into Val/Val and non-Val/Val groups. |
| Analysis Method |
For categorical variables the statistics used was chi-square test, and for continuous variables we used two way analysis of variance (ANOVA) or multiple regression analysis. All statistical analyses were conducted using SPSS ver.20.0 (SPSS, Inc., Chicago, Illinois). A significance level of 5% was set. |
| Result Description |
The occurrence of the COMT Val/Val genotype was significantly higher in children with ADHD (chi2(1)=7.13, p<0.01). However, there was no significant difference in the Val/Val genotype according to disorder, and WISC and ADHD rating scale scores, after correcting for the interaction between disorder and COMT genotype. Furthermore, no significant difference in MPH effect/adverse effects was observed in association with the COMT genotype in the ADHD group. |
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