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Cited by 93Attention Deficit Hyperactivity DisorderAutism Spectrum Disorder ResearchCognitive Abilities and Testing

Working Memory and Vigilance as Multivariate Endophenotypes Related to Common Genetic Risk for Attention-Deficit/Hyperactivity Disorder

Open access
Nigg, Joel T., Gustafsson, Hanna C., Karalunas, Sarah L., Ryabinin, Peter, McWeeney, Shannon K., Faraone, Stephen V., Mooney, Michael A., Fair, Damien A. +1 more·2018·Journal of the American Academy of Child & Adolescent Psychiatry
DOI 10.1016/j.jaac.2017.12.013PMC PMC6547382
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Abstract

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 R 2 = 0.045; β = 0.233, SE = 0.053, p = .000011) and multi-indicator dimensional ADHD latent variables by parent report (β = 0.185, SE = 0.043) and teacher report (β = 0.165, SE = 0.042). The PGS effect was statistically mediated by working memory (indirect effect, β = 0.101, SE = 0.029, 95% CI = 0.05, 0.16, p = .00049, 43% of genetic effect accounted for) and arousal/alertness (indirect effect β = 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.

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Crossref · 10.1016/j.jaac.2017.12.013

Cites

Statistics

Nothing to recompute.

Claims the paper makes

0 of 36 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    In the European-ancestry subsample (n=514), the polygenic risk score was associated with ADHD diagnosis, with beta=.233, SE=.053, p=.000011, and Nagelkerke R2=.045.

    “For the European population, the PGS was associated with ADHD diagnosis (Nagelkerke R2= .045; beta=.233, SE=.053, p=.000011)”
    • Also stated in: § Overview and sample description · boosted
      “For ADHD diagnosis, the association with the PGS was robust, beta=.233, SE=.053, OR=17.57, P=. 000011, Nagelkerke pseudo R2 = .045.”
    Quote in the paperSubstantial claim
  • Findingown data

    In the European-ancestry subsample, the polygenic risk score was associated with the parent-report ADHD latent dimension (beta=.185, SE=.043).

    “multi-indicator dimensional ADHD latent variables by parent report (beta=.185, SE=.043)”
    Quote in the paperSubstantial claim
  • Findingown data

    The inhibition latent variable showed no association with the polygenic risk score.

    “the PGS was not related to the inhibition latent variable.”
    Quote in the paperSubstantial claim
  • Findingown data

    The findings were nearly the same in the European-ancestry subgroup (n=514) and the full sample (n=656).

    “Results were essentially identical in the homogeneous European ancestry subgroup (n=514) and in the full sample (n=656).”
    Quote in the paperNot a substantial claim
  • Findingown data

    Sensitivity analyses using all available children (N=656) and the European-only subsample re-tested with a European-only polygenic score yielded very similar results.

    “Sensitivity analyses repeated with all available children (N=656) and our Euro-only subsample (n=514) was then re-tested with the polygenic score derived from an Euro-only subsample of the discovery data; all yielded very similar results, lending confidence to these observations”
    Quote in the paperNot a substantial claim
  • Classified as probably not a substantial claim. 22
  • May combine two claims. 21

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Changing the polygenic risk score threshold did not change the findings.

    “Alternative ways of computing the PGS at different thresholds (Figure S2, online) did not alter results.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Every latent cognitive variable showed a robust relationship with ADHD diagnosis and with the latent dimensional ADHD measures.

    “Consistent with a massive literature, all latent cognitive variables were robustly related to ADHD diagnosis and latent dimensional ADHD variables.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    No association was found between the polygenic risk score and sex, either in the full sample or within the ADHD group.

    “The PGS was not related to sex in the overall sample (p=.95) or within the ADHD (boys m=.405, girls m=.414, p=.57).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    For both working memory and vigilance latent variables, partial mediation was reliable across all definitions of ADHD, explaining 34% to 50% of the polygenic effect on ADHD in the models.

    “Overall, reliable partial mediation was seen for the working memory and vigilance latent variables regardless of how ADHD was defined and accounted for 34% to 50% of the polygenic effect on ADHD across models.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    For output speed and time reproduction, mediation effects were weaker and failed to survive correction given the sample size.

    “mediation effects for output speed and time reproduction were less pronounced and did not survive statistical correction at this sample size.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Across all models, working memory and vigilance-arousal were reliably and strongly associated with the polygenic risk score.

    “Working memory and vigilance-arousal had reliable and strong associations with the PGS in all models (Table 2) and so were carried forward to mediation tests.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The mental clock and slow response speed measures showed marginal links to the polygenic risk score in some models, but none survived correction.

    ““Mental clock” and slow response speed, while marginally related to the PGS at least in some models, did not survive correction in any models.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The drift rate parameter loaded on an arousal/vigilance factor together with similar signal detection theory measures (d') and mediated genetic effects on ADHD.

    “Consistent with theory, it loaded on an arousal/vigilance factor with similar measures from signal detection theory (d’) and mediated genetic effects on ADHD.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingnone given

    The working memory latent variable reflected a combination of short-term storage and maintenance, but not complex cognition or planning.

    “The working memory latent variable captured a mix of short-term store and maintenance, but not complex cognition or planning.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Latent variables capture only variance shared across tasks and are therefore free from measurement error due to unreliability.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Historically, working memory and response inhibition are the executive functions most consistently linked to ADHD.

    “The first two are executive functions (EF) that have historically been the most reliably related to ADHD - working memory6 and response inhibition.5”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [5] Barkley, 1997, Behavioral inhibition, sustained attention, and executive functions: constructing a unifying theory of ADHD, Psychol Bull source

      Not checked in the free run.

    • cites [6] Castellanos, 2002, Neuroscience of attention-deficit/hyperactivity disorder: the search for endophenotypes, Nat Rev Neurosci source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Working memory and vigilance are supported as endophenotypes for ADHD.

    “They are here supported as endophenotypes.”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: The statistical mediation model reflects a causal mediation process from genetic risk through cognitive function to ADHD, despite concurrent measurement of EF and ADHD.

  • May combine two claims.

    Study design and conductown data

    The parent and teacher ADHD measurement models fit well (parent: RMSEA=0.057, CFI=.996, TLI=.992; teacher: RMSEA=.000, CFI=1.00, TLI=1.00).

    “These two measurement models fit well (parent: RMSEA=0.057, CFI=.996, TLI=.992; teacher: RMSEA=.000, CFI=1.00 and TLI=1.00).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Working memory and vigilance are empirically and conceptually related.

    “These two domains are empirically and conceptually related, however, and it remains to be seen whether shared dependence on executive attention or other cognitive capacities further simplifies this picture.57”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [57] Shipstead, 2015, Working memory capacity and the scope and control of attention, Atten Percept Psychophys source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Vigilance, or attentional arousal, has its basis in ascending noradrenergic systems and may be the most long-standing cognitive mediator suggested for ADHD.

    “The third is attentional arousal (or vigilance), which is anchored in ascending noradrenergic neural systems7 and closely related to earlier ADHD-related proposals of arousal, activation, and gain efficiency, as well as to components of response-time variability.10 It is perhaps the most enduring cognitive mediator proposed for ADHD.11–13”
    Quote in the paperNot a substantial claim0 of 5 sources checked
    • cites [7] Petersen, 2012, The attention system of the human brain: 20 years after, Annu Rev Neurosci source

      Not checked in the free run.

    • cites [10] Karalunas, 2014, Annual research review: Reaction time variability in ADHD and autism spectrum disorders: measurement and mechanisms of a proposed trans-diagnostic phenotype, J Child Psychol Psychiatry source

      Not checked in the free run.

    • cites [11] Huang-Pollock, 2012, Evaluating vigilance deficits in ADHD: a meta-analysis of CPT performance, J Abnorm Psychol source

      Not checked in the free run.

    • cites [12] Sergeant, 2000, The cognitive-energetic model: an empirical approach to attention-deficit hyperactivity disorder, Neurosci Biobehav Rev source

      Not checked in the free run.

    • cites [13] Zentall, 1987, Self-regulation of stimulation for ADD-H children during reading and vigilance task performance, J Abnorm Child Psychol source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Output speed is of interest in ADHD.

    “The last domain is output speed, also of interest in ADHD.16”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [16] Kuntsi, 2010, Separation of cognitive impairments in attention-deficit/hyperactivity disorder into 2 familial factors, Arch Gen Psychiatry source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Finalization of the latent variables occurred without knowledge of the genetic data or polygenic risk score correlations.

    “The latent variables were finalized while blind to the genetic data or PGS correlations, however.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    Longitudinal evidence provides tentative support for a developmental mediation model linking aspects of EF to ADHD.

    “Longitudinal studies tentatively support a mediation model of development of aspects of EF and ADHD.17–20”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [17] Rabinovitz, 2016, Temperament, executive control, and attention-deficit/hyperactivity disorder across early development, J Abnorm Psychol source

      Not checked in the free run.

    • cites [18] Rajendran, 2013, Neuropsychological functioning and severity of ADHD in early childhood: a four-year cross-lagged study, J Abnorm Psychol source

      Not checked in the free run.

    • cites [19] Brocki, 2010, Interrelations between executive function and symptoms of hyperactivity/impulsivity and inattention in preschoolers: a two year longitudinal study, J Abnorm Child Psychol source

      Not checked in the free run.

    • cites [20] Tillman, 2015, A longitudinal examination of the developmental executive function hierarchy in children with externalizing behavior problems, J Atten Disord source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The mental clock, or temporal information processing, is abnormal in ADHD and linked to cerebellar-cortical-basal-ganglia circuits.

    “The fourth domain, temporal information processing or “the mental clock,” allows for rapid time perception and reproduction, and is atypical in ADHD;14 it is related to cerebellar-cortical-basal-ganglia circuitry.15”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [14] Hwang-Gu, 2015, Interval timing deficits assessed by time reproduction dual tasks as cognitive endophenotypes for attention-deficit/hyperactivity disorder, PLoS One source

      Not checked in the free run.

    • cites [15] Mauk, 2004, The neural basis of temporal processing, Annu Rev Neurosci source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Two experienced clinicians, a child psychiatrist and a child psychologist, independently established the best-estimate research diagnoses and final eligibility.

    “Best estimate research diagnoses and final eligibility were established by a team of two experienced clinicians (a child psychiatrist and a child psychologist) who independently arrived at the diagnosis.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    The Hochberg correction was employed for multiple testing.

    “Blakesley et al54 recommended the Hochberg correction55 in this case, which was therefore employed here.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [54] Blakesley, 2009, Comparisons of methods for multiple hypothesis testing in neuropsychological research, Neuropsychology source

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    • cites [55] Hochberg, 1988, A sharper Bonferroni procedure for multiple tests of significance, Biometrika source

      Not checked in the free run.

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    Study design and conductown data

    The cognitive testing occurred only after participants had washed out medications for at least 7 half-lives.

    “Children completed a second visit in which the cognitive measures were obtained after a medication washout of >= 7 half-lives.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    ADHD's genetic architecture is probably complex, involving common and rare variants plus epigenetic influences.

    “The genetic structure of ADHD is likely complex, including both common and rare genetic variants as well as epigenetic effects.25,26”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [25] Martin, 2015, The relative contribution of common and rare genetic variants to ADHD, Transl Psychiatry source

      Not checked in the free run.

    • cites [26] Lesch, 2016, Maturing insights into the genetic architecture of neurodevelopmental disorders─from common and rare variant interplay to precision psychiatry, J Child Psychol Psychiatry source

      Not checked in the free run.

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    Premisecitation

    Only one prior study used a polygenic score to examine mediation by cognitive measures on ADHD, and it failed to detect mediation.

    “While candidate gene studies have previously looked at statistical mediation by cognitive measures on ADHD,33,34 only one used a polygenic score.35 They failed to detect mediation.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [35] Benca, 2017, Predicting cognitive executive functioning with polygenic risk scores for psychiatric disorders, Behav Genet source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Polygenic risk scores have been useful for detecting common variant signals in ADHD and other conditions.

    “an approach that has proven fruitful in detecting the common variant signal for ADHD28–32 and other disorders.”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [28] Hamshere, 2013, High loading of polygenic risk for ADHD in children with comorbid aggression, Am J Psychiatry source

      Not checked in the free run.

    • cites [29] Martin, 2014, Genetic risk for attention-deficit/hyperactivity disorder contributes to neurodevelopmental traits in the general population, Biol Psychiatry source

      Not checked in the free run.

    • cites [30] Riglin, 2016, Association of genetic risk variants with attention-deficit/hyperactivity disorder trajectories in the general population, JAMA Psychiatry source

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    • cites [31] Stergiakouli, 2015, Shared genetic influences between attention-deficit/hyperactivity disorder (ADHD) traits in children and clinical ADHD, J Am Acad Child Adolesc Psychiatry source

      Not checked in the free run.

    • cites [32] Carey, 2017, Reward-related ventral striatum activity links polygenic risk for attention-deficit/hyperactivity disorder to problematic alcohol use in young adulthood, Biol Psychiatry

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    To address population stratification and power, the analysis was carried out three times.

    “To ensure that results were not due to population stratification (on one hand) and to ensure that results were not attributable to low power (on the other hand), we carried out the analysis three times.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Benca et al. did not find reliable executive function mediation of polygenic score effects on ADHD, but their discovery and target samples were smaller.

    “Benca et al35 failed to find reliable EF mediation of PGS effects on ADHD but had a smaller discovery and target sample.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [35] Benca, 2017, Predicting cognitive executive functioning with polygenic risk scores for psychiatric disorders, Behav Genet source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    For the full sample, the analysis adjusted for the first 10 genetic principal components to address population stratification.

    “In the analyses that considered the full sample (n=656), the first 10 genetic principal components were also controlled (from both the cognitive and ADHD measures), in order to control for effects of population stratification.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Latent variables are theorized to eliminate task impurity in laboratory tasks, and twin data suggest they yield the strongest genetic signal compared with individual task variables.

    “They are also theorized to remove the inherent task impurity in laboratory tasks; twin data suggest they provide the strongest genetic signal versus individual task variables.58”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [58] Friedman, 2008, Individual differences in executive functions are almost entirely genetic in origin, J Exp Psychol Gen source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductreasoning

    A case-control design, rather than a population sample, was used, which allowed enrichment for ADHD cases and greater variation in ADHD psychopathology.

    “Second, we used a case-control design, not a population sample; this enabled us to enrich our sample for ADHD cases and ensure a stronger variation of ADHD psychopathology than otherwise.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Results were nearly identical across all models, so population stratification cannot explain the findings.

    “Results were nearly identical in all models, so population stratification cannot account for these results.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    Analyses were repeated with the full sample while covarying genetic principal components as a partial control for stratification.

    “However, to ensure those results were not attributable to reduced power in that restricted sample, we repeated analyses with the full sample while covarying the genetic principal components as a partial (but potentially inadequate) control of stratification (see online supplement for more discussion of this point).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    ADHD is likely heterogeneous in mediating cognitive mechanisms, comorbidity, severity, clinical course, temporal variation, environmental exposures, and probably genetic variation.

    “While effects were relatively consistent across formulations of ADHD here, ADHD is likely to be heterogeneous with regard to mediating cognitive mechanisms64,65 as well as with regard to comorbidity, severity, clinical course, temporal variation, environmental exposures, and probably genetic variation.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [64] Nigg, 2005, Neuropsychologic theory and findings in attention-deficit/hyperactivity disorder: the state of the field and salient challenges for the coming decade, Biol Psychiatry source

      Not checked in the free run.

    • cites [65] Fair, 2012, Distinct neuropsychological subgroups in typically developing youth inform heterogeneity in children with ADHD, Proc Natl Acad Sci U S A source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The full information maximum likelihood model in MPLUS 7.2 was used to handle missing data.

    “Missing data were handled using the full information maximum likelihood model in MPLUS 7.2.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductown data

    Models were tested in multiple ways, with the primary model restricted to a homogeneous Caucasian-European ancestry test sample.

    “To address the possibility of bias due to mixed ancestry populations, we tested our models in multiple ways, with our primary model restricted to a homogeneous Caucasian-European ancestry test sample.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    A check indicated that differential distributions of executive function scores or polygenic scores across ADHD and control groups were unlikely to cause false negatives, as histograms were approximately normal and ADHD group by polygenic score interactions predicting working memory or arousal were not significant (all p > .25).

    “A check on this possibility suggested this was not the case, as histograms appear approximately normal across groups (See Figure S3 and S6 online) and interactions of ADHD group with PGS in predicting working memory or arousal were not significant (all p>.25).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Sex and age were covaried in all reported results.

    “We covaried sex and age in all results reported.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    A sensitivity analysis used a modified polygenic score based only on a European-ancestry discovery sample.

    “Finally, because we do not know whether a heterogeneous discovery sample may bias results, a further sensitivity analysis was conducted with a modified polygenic score using only a European-ancestry discovery sample.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Kamradt reported, in a different sample using a candidate gene approach, that response inhibition mediated the effect of polymorphisms at DRD4 and DAT1.

    “Kamradt34 reported in a different sample using a candidate gene approach that response inhibition mediated the effect of polymorphisms at DRD4 and DAT1.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [34] Kamradt, 2016, Neuropsychological performance measures as intermediate phenotypes for attention-deficit/hyperactivity disorder: a multiple mediation analysis, Dev Psychopathol source

      Not checked in the free run.

38 of 38

  • The paper relies on this without support.

    ADHD is associated with atypical cognitive functions.

    “Attention Deficit Hyperactivity Disorder (ADHD) is associated with atypical cognitive functions.”

  • The authors state this as an assumption.

    The statistical mediation model reflects a causal mediation process from genetic risk through cognitive function to ADHD, despite concurrent measurement of EF and ADHD.

    “We, therefore, test this claim in a path model environment using conventions accepted for this purpose21, and use the term “mediation” for simplicity, although EF and ADHD are measured concurrently herein.”

  • The paper relies on this without support.

    Latent variables capture only variance shared across tasks and are therefore free from measurement error due to unreliability.

    “Latent variables reflect only variance correlated across tasks and so are free from measurement error due to unreliability.”

  • The paper relies on this without support.

    The drift rate parameter has shown the largest ADHD effects in prior studies.

    “We emphasized the drift rate parameter because it has shown the largest ADHD effects in prior studies.”
4 of 4

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Working memory is probably one of the core cognitive deficits in the pathophysiology of all ADHD subtypes and could be a reasonable target for ADHD treatment.

    “this is in line with a recently introduced model of ADHD psychopathology, which proposes WM deficits as a major risk factor in ADHD [51] and implies that WM is probably one of the core cognitive deficits in the pathophysiology of all ADHD subtypes, and could be a reasonable target for ADHD treatment.”

    From ADHD subtype-specific cognitive correlates and association with self-esteem: a quantitative difference (2020) · cites this paper as [51]

    The Discussion reports that alterations in working memory and vigilance statistically account for part of the common genetic risk associated with ADHD, supporting working memory as a possible intermediate phenotype. It does not establish working-memory deficits as a major risk factor across all ADHD subtypes or evaluate working memory as a treatment target; those are extensions beyond the source's findings. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • European-subgroup model is labeled with the full-sample size

    Minor

    The text says the first confirmatory factor analysis is for the 514-child subgroup, but its chi-square statistic labels the sample as N=656.

1 of 1

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References 64 · Cited by 93

Research works printed but not linked: 2

  1. Browne, 1993, Alternative ways of assessing model fit, Sage Focus Editions, 154
  2. Friedman, 2008, Individual differences in executive functions are almost entirely genetic in origin, J Exp Psychol Gen, 137, 201, 10.1037/0096-3445.137.2.201 · DOI · Paper page

Authors
Nigg, J. T., Gustafsson, H. C., Karalunas, S. L., Ryabinin, P., McWeeney, S. K., Faraone, S. V., Mooney, M. A., Fair, D. A., & Wilmot, B.
Affiliations
  • Oregon Health & Science University (US)
  • SUNY Upstate Medical University (US)
Corresponding author
Nigg, Joel T.
ORCID
Venue
Journal of the American Academy of Child & Adolescent Psychiatry
Publisher
Elsevier BV
Published
2018-03
Volume
57
Issue
3
Pages
175-182
ISSN
0890-8567 (ISSN-L)
DOI
10.1016/j.jaac.2017.12.013
PMC
PMC6547382
OpenAlex
W2784318189
Cited by
93
References
64
Citations by year
2026: 6 · 2025: 3 · 2024: 6 · 2023: 12 · 2022: 13 · 2021: 19 · 2020: 17 · 2019: 11 · 2018: 5 · 2017: 1
FWCI
10.23
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Journal of the American Academy of Child & Adolescent Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (5r01mh099064-05)
  • National Institute of Mental Health (R01-MH099064, R01MH115357, U01MH109536, R37MH059105)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Cognitive Abilities and Testing
Keywords
attention deficit hyperactivity disorder, working memory, sustained attention, arousal regulation, cognitive endophenotypes, polygenic risk score, mediation analysis, common genetic variants, children, executive function, response inhibition, processing speed
MeSH terms
Arousal, Attention Deficit Disorder with Hyperactivity, Child, Female, Humans, Male, Memory, Short-Term, Neuropsychological Tests, Case-Control Studies, Multifactorial Inheritance, Executive Function, Endophenotypes

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