Summary |
In this study, they reported an additional family-based study of DRD4 exon III repeat region and ADHD. However, in the current study they fail to observe preferential transmission of the DRD4 exon III long 7 repeat allele, X2=0.142, P<0.1, df=1. Nor was any preferential transmission observed when genotypes were compared, X2=0.180, P>0.1, df=1. Possible reasons are discussed, especially lack of sufficient power in analying more refined phenotypes, why the current results in contrast to previous findings fail to support a role for the long form of the DRD4 receptor as a putative risk factor for ADHD. |
Total Sample |
46 nuclear families (probands and parents) were studied. The percentage of probands with ADHD combined type was 57%, inattentive 33%, impulsive 10%. Among probands participating in the study 39% met criteria for comorbid oppositional defiance disorder or conduct disorder. Transient tics were displayed in 18% of the probands. |
Sample Collection |
In the current report 46 nuclear families (probands and parents) were studied. As previously described [Eisenberg et al., 1999], ADHD subjects and their families were recruited for participation in this study from a child psychiatry unit in a community mental health center and from several child neurology clinics in the Jerusalem municipal area. Subjects included both Ashkenazi and non-Ashkenazi Jews. This study was approved by the Ethics Committee of the Herzog Hospital and informed consent was obtained from participating subjects. |
Diagnosis Description |
The criteria for eligibility included Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria according to the K-SAD-PL (Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version). The first informant on the proband's behavior was the mother, who was interviewed using the K-SAD-PL. The second informant (the teacher) used the Conners Teacher Rating scale to evaluate the proband's behavior. In borderline cases (when the DSM-IV criteria were not completely met or when the Conner's index was below 1.5) the child was interviewed by a senior psychiatrist and a consensus diagnosis arrived at. The DSM IV recognizes three types of ADHD: ADHD-Predominantly Inattentive Type I, ADHD-Predominantly Hyperactive Impulse Type II, and ADHD-Combined Type 3. Probands were also administered the Continuous Performance test (CPT). CPT False Alarm score (considered a measure of impulsivity) equals the errors of commission divided by the number of nontarget stimuli. Hit rate (considered a measure of inattention) equals the number of correct responses divided by the number of target stimuli. Cases with a primary diagnosis of comorbid Tourette's syndrome, pervasive developmental disorder, physically handicapped, psychosis, mental retardation, epilepsy, hyperthyroidism, evidence or history of child abuse, and adoption were excluded. IQ was determined by WISC and children with an IQ less than 80 were excluded. |
Technique |
The exon III repeat region of the DRD4 receptor was characterized as previously described [Ebstein et al., 1996]. It should be noted that in this cohort 15/16 probands with the long alleles (6-8 repeats) were distinguished by the 7 repeat. Only 1 subject had an 8 repeat. They included all the probands and controls with the long repeat (6-8) together and in essence, they therefore compared 7 versus non-7 repeats. |
Analysis Method |
In the current report they studied 46 nuclear families (probands and parents) for the DRD4 exon III repeat polymorphism using the robust haplotype relative risk and a parent to proband allele transmission test design that neutralizes the problem of population stratification [Ewens and Spielman, 1995; Falk and Rubenstein, 1987]. |
Result Description |
No preferential transmission of the long DRD4 alleles was observed in families that were studied. The percentage of the long alleles was 16.3% in the proband group and 18.4% in the haplotype control (non-transmitted) group, X2=0.14, P=0.71, df=1. |