Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, starting in early childhood and persisting into adulthood in the majority of cases. Family and twin studies have demonstrated the importance of genetic factors and candidate gene association studies have identified several loci that exert small but significant effects on ADHD. To provide further clarification of reported associations and identify novel associated genes, we examined 1038 single-nucleotide polymorphisms (SNPs) spanning 51 candidate genes involved in the regulation of neurotransmitter pathways, particularly dopamine, norepinephrine and serotonin pathways, in addition to circadian rhythm genes. Analysis used within family tests of association in a sample of 776 DSM-IV ADHD combined type cases ascertained for the International Multi-centre ADHD Gene project. We found nominal significance with one or more SNPs in 18 genes, including the two most replicated findings in the literature: DRD4 and DAT1. Gene-wide tests, adjusted for the number of SNPs analysed in each gene, identified associations with TPH2, ARRB2, SYP, DAT1, ADRB2, HES1, MAOA and PNMT. Further studies will be needed to confirm or refute the observed associations and their generalisability to other samples. Molecular Psychiatry (2006) 11, 934-953.
The data are inconsistent with models that consider RT variability as reflecting a stable cognitive deficit in ADHD, but instead emphasize the extent to which energetic or motivational factors can have a greater effect on RT performance in ADHD. The findings support the role of RT variability as an endophenotype mediating the link between genes and ADHD.
Children with attention deficit/hyperactivity disorder (ADHD) choose smaller sooner (SS) over larger later (LL) rewards more than controls. Here we assess the contributions of impulsive drive for immediate rewards (IDIR) and delay aversion (DAv) to this pattern. We also explore the characteristics of, and the degree of familiality in, ADHD SS responders. We had 360 ADHD probands; 349 siblings and 112 controls (aged between 6 to 17 years) chose between SS (1 point after 2 s) and LL reward (2 points after 30 s) outcomes on the Maudsley Index of Delay Aversion (Kuntsi, Oosterlaan, Stevenson, 2001): Under one condition SS choice led to less overall trial delay under another it did not. ADHD participants chose SS more than controls under both conditions. This effect was larger when SS choice reduced trial delay. ADHD SS responders were younger, had lower IQ, more conduct disorder and had siblings who were more likely to be SS responders themselves. The results support a dual component model in which both IDIR and DAv contribute to SS choice in ADHD. SS choice may be a marker of an ADHD motivational subtype. (PsycINFO Database Record (c) 2009 APA, all rights reserved).
The resting electroencephalogram (EEG) reflects development and arousal, but whether it can support clinical diagnosis of attention-deficit/hyperactivity disorder (ADHD) remains controversial. Here we examined whether theta power and theta/beta ratio are consistently elevated in ADHD and younger age as proposed. Topographic 48-channel EEG from 32 children (8-16 years) and 22 adults (32-55 years) with ADHD and matched healthy controls (n = 30 children/21 adults) was compared. Following advanced artefact correction, resting EEG was tested for increased theta and theta/beta activity due to ADHD and due to normal immaturity. Discriminant analyses tested classification performance by ADHD and age using these EEG markers as well as EEG artefacts and deviant attentional event-related potentials (ERPs). No consistent theta or theta/beta increases were found with ADHD. Even multivariate analyses indicated only marginal EEG power increases in children with ADHD. Instead, consistent developmental theta decreases were observed, indicating that maturational lags of fewer than 3 years would have been detected in children. Discriminant analysis based on proposed simple spectral resting EEG markers was successful for age but not for ADHD (81 vs. 53 % accuracy). Including ERP markers and EEG artefacts improved discrimination, although not to diagnostically useful levels. The lack of consistent spectral resting EEG abnormalities in ADHD despite consistent developmental effects casts doubt upon conventional neurometric approaches towards EEG-based ADHD diagnosis, but is consistent with evidence that ADHD is a heterogeneous disorder, where the resting state is not consistently characterised by maturational lag.
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