Separation of genetic influences on attention deficit hyperactivity disorder symptoms and reaction time performance from those on IQ

MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, UK.
Psychological Medicine (Impact Factor: 5.94). 09/2009; 40(6):1027-37. DOI: 10.1017/S003329170999119X
Source: PubMed


Attention deficit hyperactivity disorder (ADHD) shows a strong phenotypic and genetic association with reaction time (RT) variability, considered to reflect lapses in attention. Yet we know little about whether this aetiological pathway is shared with other affected cognitive processes in ADHD, such as lower IQs or the generally slower responses (mean RTs). We aimed to address the question of whether a shared set of genes exist that influence RT variability, mean RT, IQ and ADHD symptom scores, or whether there is evidence of separate aetiological pathways.
Multivariate structural equation modelling on cognitive tasks data (providing RT data), IQ and ADHD ratings by parents and teachers collected on general population sample of 1314 twins, at ages 7-10 years.
Multivariate structural equation models indicated that the shared genetic influences underlying both ADHD symptom scores and RT variability are also shared with those underlying mean RT, with both types of RT data largely indexing the same underlying liability. By contrast, the shared genetic influences on ADHD symptom scores and RT variability (or mean RT) are largely independent of the genetic influences that ADHD symptom scores share with IQ.
The finding of unique aetiological pathways between IQ and RT data, but shared components between mean RT, RT variability and ADHD symptom scores, illustrates key influences in the genetic architecture of the cognitive and energetic processes that underlie the behavioural symptoms of ADHD. In addition, the multivariate genetic model fitting findings provide valuable information for future molecular genetic analyses.

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Available from: Jaap J van der Meere, Jul 25, 2014
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    • "Cognitive variables were further regressed for IQ. Although our previous analyses indicated that the majority of genetic influences shared between ADHD and cognitive variables were independent of those shared with IQ (Wood et al. 2010, 2011), regressing for IQ ensured we controlled for any small mediating effects of IQ that were not the focus of present analyses, consistent with our previously adopted approach (Kuntsi et al. 2010, 2014). "
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    ABSTRACT: Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorders (ASDs) frequently co-occur. However, due to previous exclusionary diagnostic criteria, little is known about the underlying causes of this covariation. Twin studies assessing ADHD symptoms and autistic-like traits (ALTs) suggest substantial genetic overlap, but have largely failed to take into account the genetic heterogeneity of symptom subscales. This study aimed to clarify the phenotypic and genetic relations between ADHD and ASD by distinguishing between symptom subscales that characterise the two disorders. Moreover, we aimed to investigate whether ADHD-related cognitive impairments show a relationship with ALT symptom subscales; and whether potential shared cognitive impairments underlie the genetic risk shared between the ADHD and ALT symptoms. Multivariate structural equation modelling was conducted on a population-based sample of 1312 twins aged 7-10. Social-communication ALTs correlated moderately with both ADHD symptom domains (phenotypic correlations around 0.30) and showed substantial genetic overlap with both inattention and hyperactivity-impulsivity (genetic correlation = 0.52 and 0.44, respectively). In addition to previously reported associations with ADHD traits, reaction time variability (RTV) showed significant phenotypic (0.18) and genetic (0.32) association with social-communication ALTs. RTV captured a significant proportion (24 %) of the genetic influences shared between inattention and social-communication ALTs. Our findings suggest that social-communication ALTs underlie the previously observed phenotypic and genetic covariation between ALTs and ADHD symptoms. RTV is not specific to ADHD symptoms, but is also associated with social-communication ALTs and can, in part, contribute to an explanation of the co-occurrence of ASD and ADHD.
    Journal of Abnormal Child Psychology 05/2015; DOI:10.1007/s10802-015-0037-4 · 3.09 Impact Factor
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    • "To try to address this, some studies calculate the coefficient of variation: SDRT/mean RT. However, if the RT variance and mean are driven by the same mechanism, then the coefficient of variation would not clarify matters (Karalunas & Huang-Pollock, 2013; Karalunas, Huang-Pollock, & Nigg, 2012a; Klein, et al., 2006; Wagenmakers, et al., 2005; Wood, et al., 2010). "
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    ABSTRACT: Background Intraindividual variability in reaction time (RT) has received extensive discussion as an indicator of cognitive performance, a putative intermediate phenotype of many clinical disorders, and a possible trans-diagnostic phenotype that may elucidate shared risk factors for mechanisms of psychiatric illnesses. Scope and MethodologyUsing the examples of attention deficit hyperactivity disorder (ADHD) and autism spectrum disorders (ASD), we discuss RT variability. We first present a new meta-analysis of RT variability in ASD with and without comorbid ADHD. We then discuss potential mechanisms that may account for RT variability and statistical models that disentangle the cognitive processes affecting RTs. We then report a second meta-analysis comparing ADHD and non-ADHD children on diffusion model parameters. We consider how findings inform the search for neural correlates of RT variability. FindingsResults suggest that RT variability is increased in ASD only when children with comorbid ADHD are included in the sample. Furthermore, RT variability in ADHD is explained by moderate to large increases (d = 0.63–0.99) in the ex-Gaussian parameter τ and the diffusion parameter drift rate, as well as by smaller differences (d = 0.32) in the diffusion parameter of nondecision time. The former may suggest problems in state regulation or arousal and difficulty detecting signal from noise, whereas the latter may reflect contributions from deficits in motor organization or output. The neuroimaging literature converges with this multicomponent interpretation and also highlights the role of top-down control circuits. Conclusion We underscore the importance of considering the interactions between top-down control, state regulation (e.g. arousal), and motor preparation when interpreting RT variability and conclude that decomposition of the RT signal provides superior interpretive power and suggests mechanisms convergent with those implicated using other cognitive paradigms. We conclude with specific recommendations for the field for next steps in the study of RT variability in neurodevelopmental disorders.
    Journal of Child Psychology and Psychiatry 03/2014; 55(6). DOI:10.1111/jcpp.12217 · 6.46 Impact Factor
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    • "This increase in interest is in part due to evidence that ISV reflects a stable trait [10-12] and possibly a unitary construct that generalises across a broad range of tasks and sensory modalities [7,13,14]. Furthermore, ISV is both familial [15,16] and hereditary [17,18], thus qualifying as a candidate endophenotype of ADHD [1,19]. "
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    ABSTRACT: Increased intra-subject variability of reaction times (ISV-RT) is one of the most consistent findings in attention-deficit/hyperactivity disorder (ADHD). Although the nature of this phenomenon is still unclear, it has been hypothesised to reflect interference from the Default Mode Network (DMN). So far, ISV-RT has been operationally defined either as a frequency spectrum of the underlying RT time series, or as a measure of dispersion of the RT scores distribution. Here, we use a novel RT analysis framework to link these hitherto unconnected facets of ISV-RT by determining the sensitivity of different measures of RT dispersion to the frequency content of the underlying RT time series. N=27 patients with ADHD and N=26 healthy controls performed several visual N-back tasks. Different measures of RT dispersion were repeatedly modelled after individual frequency bands of the underlying RT time series had been either extracted or suppressed using frequency-domain filtering. We found that the intra-subject standard deviation of RT preserves the "1/f noise" characteristic typical of human RT data. Furthermore and most importantly, we found that the ex-Gaussian parameter τ is rather exclusively sensitive to frequencies below 0.025 Hz in the underlying RT time series and that the particularly slow RTs, which nourish τ, occur regularly as part of an quasi-periodic, ultra-slow RT fluctuation. Overall, our results are compatible with the idea that ISV-RT is modulated by an endogenous, slowly fluctuating process that may reflect DMN interference.
    PLoS ONE 10/2013; 8(10):e69674. DOI:10.1371/journal.pone.0069674 · 3.23 Impact Factor
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