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Interval timing deficits assessed by time reproduction dual tasks as cognitive endophenotypes for attention-deficit/hyperactivity disorder.

ABSTRACT: The literature has suggested timing processing as a potential endophenotype for attention deficit/hyperactivity disorder (ADHD); however, whether the subjective internal clock speed presented by verbal estimation and limited attention capacity presented by time reproduction could be endophenotypes for ADHD is still unknown. We assessed 223 youths with DSM-IV ADHD (age range: 10-17 years), 105 unaffected siblings, and 84 typically developing (TD) youths using psychiatric interviews, intelligence tests, verbal estimation and time reproduction tasks (single task and simple and difficult dual tasks) at 5-second, 12-second, and 17-second intervals. We found that youths with ADHD tended to overestimate time in verbal estimation more than their unaffected siblings and TD youths, implying that fast subjective internal clock speed might be a characteristic of ADHD, rather than an endophenotype for ADHD. Youths with ADHD and their unaffected siblings were less precise in time reproduction dual tasks than TD youths. The magnitude of estimated errors in time reproduction was greater in youths with ADHD and their unaffected siblings than in TD youths, with an increased time interval at the 17-second interval and with increased task demands on both simple and difficult dual tasks versus the single task. Increased impaired time reproduction in dual tasks with increased intervals and task demands were shown in youths with ADHD and their unaffected siblings, suggesting that time reproduction deficits explained by limited attention capacity might be a useful endophenotype of ADHD.

SUBMITTER: Hwang-Gu SL

PROVIDER: S-EPMC4436371 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Interval timing deficits assessed by time reproduction dual tasks as cognitive endophenotypes for attention-deficit/hyperactivity disorder.

Hwang-Gu Shoou-Lian SL Gau Susan Shur-Fen SS

PloS one 20150518 5

The literature has suggested timing processing as a potential endophenotype for attention deficit/hyperactivity disorder (ADHD); however, whether the subjective internal clock speed presented by verbal estimation and limited attention capacity presented by time reproduction could be endophenotypes for ADHD is still unknown. We assessed 223 youths with DSM-IV ADHD (age range: 10-17 years), 105 unaffected siblings, and 84 typically developing (TD) youths using psychiatric interviews, intelligence ...[more]

PMID: 25992899

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Project description:OBJECTIVE:Disruptive mood dysregulation disorder (DMDD), characterized by severe irritability, and attention-deficit/hyperactivity disorder (ADHD) are highly comorbid. This is the first study to characterize neural and behavioral similarities and differences in attentional functioning across these disorders. METHOD:Twenty-seven healthy volunteers, 31 patients with DMDD, and 25 patients with ADHD (8 to 18 years old) completed a functional magnetic resonance imaging attention task. Group differences in intra-subject variability in reaction time (RT) were examined. The present functional magnetic resonance imaging analytic approach precisely quantified trial-wise associations between RT and brain activity. RESULTS:Group differences manifested in the relation between RT and brain activity (all regions: p < .01, F > 2.54, partial eta-squared [?p2] > 0.06). Patients with DMDD showed specific alterations in the right paracentral lobule, superior parietal lobule, fusiform gyrus, and cerebellar culmen. In contrast, patients with DMDD and those with ADHD exhibited blunted compensatory increases in activity on long RT trials. In addition, youth with DMDD exhibited increased activity in the postcentral gyrus, medial frontal gyrus, and cerebellar tonsil and declive (all regions: p < .05, F > 2.46, ?p2 > 0.06). Groups in the imaging sample did not differ significantly in intra-subject variability in RT (F2,79 = 2.664, p = .076, ?p2 = 0.063), although intra-subject variability in RT was significantly increased in youth with DMDD and ADHD when including those not meeting strict motion and accuracy criteria for imaging analysis (F2,96 = 4.283, p = .017, ?p2 = 0.083). CONCLUSION:Patients with DMDD exhibited specific alterations in the relation between pre-stimulus brain activity and RT. Patients with DMDD and those with ADHD exhibited similar blunting of compensatory neural activity in frontal, parietal, and other regions. In addition, patients with DMDD showed increased RT variability compared with healthy youth. This work is the first to identify common and unique behavioral and neural signatures of DMDD and ADHD.

Project description:OBJECTIVE:Understanding the role of endophenotypes is essential for process models of psychopathology. This study examined which candidate cognitive endophenotypes statistically mediate common variant genetic risk for attention-deficit/hyperactivity disorder (ADHD). METHOD:A case-control design using community-recruited volunteer children 7 to 11 years of age (n = 656, n = 435 ADHD), of whom 514 were of homogenous European ancestry for the primary models (n = 337 ADHD, 177 non-ADHD). Children were assessed with a multi-informant, best-estimate diagnostic procedure and laboratory measures of working memory, response inhibition, executive functioning, arousal/attention, temporal information processing, and processing speed. Latent variables were created for the candidate cognitive measures and for parent- and teacher-rated ADHD dimensions. Polygenic risk scores (PGS) were computed using a discovery sample of 20,183 individuals with ADHD and 35,191 controls from the Psychiatric Genetics Consortium. Cognitive measures that survived multiple testing correction for association with the PGS were evaluated for mediation with ADHD using structural equation models. RESULTS:Results were essentially identical in the homogeneous European ancestry subgroup (n = 514) and in the full sample (N = 656). For the European population, the PGS was associated with ADHD diagnosis (Nagelkerke R2 = 0.045; ? = 0.233, SE = 0.053, p = .000011) and multi-indicator dimensional ADHD latent variables by parent report (? = 0.185, SE = 0.043) and teacher report (? = 0.165, SE = 0.042). The PGS effect was statistically mediated by working memory (indirect effect, ? = 0.101, SE = 0.029, 95% CI = 0.05, 0.16, p = .00049, 43% of genetic effect accounted for) and arousal/alertness (indirect effect ? = 0.115, 95% CI = 0.04, 0.20, SE = 0.041, p = .005, 49% of genetic effect accounted for). CONCLUSION:This is the first clear demonstration from molecular genetic data that working memory and arousal regulation are promising cognitive endophenotypes for ADHD with regard to mediating genetic risk from common genetic variants.

Project description:Transcranial direct current stimulation (tDCS) is a promising method for altering cortical excitability with clinical implications in neuropsychiatric diseases. Its application in neurodevelopmental disorders especially attention-deficit hyperactivity disorder (ADHD), is in early stage and promising but its effectiveness has not been systematically examined yet. We conducted a meta-analysis on the effectiveness of tDCS on the most studied neuropsychological symptoms of ADHD, which is the first reported meta-analysis of tDCS studies on ADHD. Data from 10 randomized controlled studies (including 11 separate experiments) targeting inhibitory control, and/or working memory (WM) in ADHD were included. Results show that overall tDCS significantly improved inhibitory control. Sub-analyses further show that dorsolateral prefrontal cortex (dlPFC) (but not right inferior frontal gyrus) tDCS and anodal (but not cathodal) tDCS significantly improved inhibitory control with a small effect size. Anodal dlPFC-tDCS had the largest significant effect on inhibitory control with a small-to-medium effect size. Additionally, a significant improving effect of tDCS on inhibitory control accuracy (but not response time) and WM speed (but not accuracy) were found. Overall, this meta-analysis supports a beneficial effect of tDCS on inhibitory control and WM in ADHD with a small-to-medium effect size. TDCS seems to be a promising method for improving neuropsychological and cognitive deficits in ADHD. However, there might be a dissociation between neuropsychological deficits and clinical symptoms of ADHD and therefore, the significance of this meta-analysis for clinical purposes is limited. Future studies should systematically evaluate the role of inter-individual factors (i.e., ADHD subtype, types of the deficit) and stimulation parameters (i.e., site, polarity, intensity, duration, repetition rate) on tDCS efficacy in ADHD population and examine whether benefits are long-term.

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Interval timing deficits assessed by time reproduction dual tasks as cognitive endophenotypes for attention-deficit/hyperactivity disorder.

Publications

Interval timing deficits assessed by time reproduction dual tasks as cognitive endophenotypes for attention-deficit/hyperactivity disorder.

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