PubMed · 10479815
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
L McAuley. ADHD.. https://doi.org/10.1097/00005721-199909000-00020
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
There is considerable evidence to support a role of dopamine-related genes in the molecular aetiology of attention-deficit hyperactivity disorder (ADHD). A microsatellite located near the dopamine D5 receptor (DRD5) gene has been associated with ADHD in a number of studies, but other polymorphisms within the vicinity of this gene have not been examined. In this study we genotyped three microsatellites spanning the DRD5 region in a large clinical sample. Overall, we found little evidence to support a role for DRD5 in ADHD. We found no evidence of association with either the previously associated DRD5 marker, or a repeat in the promoter region of the gene. We did, however, find significant association for an allele of D4S615, a dinucleotide repeat located 131 kb 3' of DRD5 that has been previously associated with schizophrenia. A global test incorporating all alleles of this marker, however, was not significant and thus this finding needs replication before any conclusions can be made.
Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable, heterogeneous disorder of early onset, consisting of a triad of symptoms: inattention, hyperactivity, and impulsivity. The disorder has a significant genetic component, and theories of etiology include abnormalities in the dopaminergic system, with DRD4, DAT1, SNAP25, and DRD5 being implicated as major susceptibility genes. An initial report of association between ADHD and the common 148-bp allele of a microsatellite marker located 18.5 kb from the DRD5 gene has been followed by several studies showing nonsignificant trends toward association with the same allele. To establish the postulated association of the (CA)(n) repeat with ADHD, we collected genotypic information from 14 independent samples of probands and their parents, analyzed them individually and, in the absence of heterogeneity, analyzed them as a joint sample. The joint analysis showed association with the DRD5 locus (P=.00005; odds ratio 1.24; 95% confidence interval 1.12-1.38). This association appears to be confined to the predominantly inattentive and combined clinical subtypes.
OBJECTIVE: Auditory cognitive evoked potential (P300) topography predicts robust response to the stimulant pemoline in patients with attention-deficit/hyperactivity disorder (ADHD). Patients with a right fronto-central to parietal (FC2:P4) auditory P300 amplitude ratio >0.5 respond robustly to pemoline, whereas others do not. This study was performed to demonstrate whether the same test and ratio predict treatment response to methylphenidate. METHODS: Patients aged 6-12 with DSM-IV diagnosis of ADHD were administered auditory and visual cognitive evoked potential (P300) testing. They then underwent single-blind treatment with an extended-release version of methylphenidate. Robust response was defined as a 60% decrease from baseline in a parent rated ADHD rating scale. RESULTS: Nine of 20 subjects responded robustly. They did not differ from the non-robust responders in age, baseline attention or hyperactivity ratings, or any P300 parameter except auditory P300 topography. A FC2:P4 auditory P300 amplitude ratio >0.5 predicted robust response with a positive predictive value of 0.67 and a negative predictive value of 0.73. CONCLUSIONS: The ratio of right fronto-central to parietal auditory P300 amplitude predicts response to stimulants in patients with ADHD. As non-stimulant treatments are approved for the treatment of ADHD, tests such as this may help pinpoint whether to use a stimulant or a medicine with some other mechanism of action.