Hostname: page-component-cd9895bd7-mkpzs Total loading time: 0 Render date: 2024-12-23T00:36:23.508Z Has data issue: false hasContentIssue false
  • English
  • Français

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

Published online by Cambridge University Press:  15 September 2009

A. C. Wood ,
P. Asherson ,
J. J. van der Meere  and
J. Kuntsi
A. C. Wood*
Affiliation:
MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, UK
P. Asherson
Affiliation:
MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, UK
J. J. van der Meere
Affiliation:
Department of Developmental and Experimental Clinical Psychology, University of Groningen, The Netherlands
J. Kuntsi
Affiliation:
MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, UK
*
*Address for correspondence: Miss A. C. Wood, MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, UK. (Email: [email protected])
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

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.

Method

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.

Results

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.

Conclusions

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.

Keywords

ADHDgeneticsIQreaction timereaction time variability
Type
Original Articles
Information
Psychological Medicine , Volume 40 , Issue 6 , June 2010 , pp. 1027 - 1037
Copyright
Copyright © Cambridge University Press 2009

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Andreou, P, Neale, BM, Chen, W, Christiansen, H, Gabriels, I, Heise, A, Meidad, S, Muller, UC, Uebel, H, Banaschewski, T, Manor, I, Oades, R, Roeyers, H, Rothenberger, A, Sham, P, Steinhausen, HC, Asherson, P, Kuntsi, J (2007). Reaction time performance in ADHD: improvement under fast-incentive condition and familial effects. Psychological Medicine 37, 1703–1715.Google Scholar
Bellgrove, MA, Hawi, Z, Kirley, A, Gill, M, Robertson, IH (2005). Dissecting the attention deficit hyperactivity disorder (ADHD) phenotype: sustained attention, response variability and spatial attentional asymmetries in relation to dopamine transporter (DAT1) genotype. Neuropsychologia 43, 1847–1857.Google Scholar
Bellgrove, MA, Hester, R, Garavan, H (2004). The functional neuroanatomical correlates of response variability: evidence from a response inhibition task. Neuropsychologia 42, 1910–1916.CrossRefGoogle ScholarPubMed
Bidwell, LC, Willcutt, EG, Defries, JC, Pennington, BF (2007). Testing for neuropsychological endophenotypes in siblings discordant for attention-deficit/hyperactivity disorder. Biological Psychiatry 62, 991–998.CrossRefGoogle ScholarPubMed
Borger, N, van der Meere, J (2000). Motor control and state regulation in children with ADHD: a cardiac response study. Biological Psychology 51, 247–267.CrossRefGoogle ScholarPubMed
Castellanos, FX, Tannock, R (2002). Neuroscience of attention-deficit/hyperactivity disorder: the search for endophenotypes. Nature Reviews Neuroscience 3, 617–628.Google Scholar
Conners, CK, Sitarenios, G, Parker, JD, Epstein, JN (1998 a). The revised Conners' Parent Rating Scale (CPRS-R): factor structure, reliability, and criterion validity. Journal of Abnormal Child Psychology 26, 257–268.CrossRefGoogle ScholarPubMed
Conners, CK, Sitarenios, G, Parker, JD, Epstein, JN (1998 b). Revision and restandardization of the Conners' Teacher Rating Scale (CTRS-R): factor structure, reliability, and criterion validity. Journal of Abnormal Child Psychology 26, 279–291.CrossRefGoogle ScholarPubMed
Faraone, SV, Perlis, RH, Doyle, AE, Smoller, JW, Goralnick, JJ, Holmgren, MA, Sklar, P (2005). Molecular genetics of attention-deficit/hyperactivity disorder. Biological Psychiatry 57, 1313–1323.CrossRefGoogle ScholarPubMed
Johnson, KA, Kelly, SP, Bellgrove, MA, Barry, E, Cox, M, Gill, M, Robertson, IH (2007). Response variability in attention deficit hyperactivity disorder: evidence for neuropsychological heterogeneity. Neuropsychologia 45, 630–638.CrossRefGoogle ScholarPubMed
Johnson, KA, Wiersema, JR, Kuntsi, J (2009). What would Karl Popper say? Are current psychological theories of ADHD falsifiable? Behavioral and Brain Functions 5, 15.CrossRefGoogle Scholar
Klein, C, Wendling, K, Huettner, P, Ruder, H, Peper, M (2006). Intra-subject variability in attention-deficit hyperactivity disorder. Biological Psychiatry 60, 1088–1097.CrossRefGoogle ScholarPubMed
Kuntsi, J, Andreou, P, Ma, J, Borger, NA, van der Meere, JJ (2005). Testing assumptions for endophenotype studies in ADHD: reliability and validity of tasks in a general population sample. BMC Psychiatry 5, 40.CrossRefGoogle Scholar
Kuntsi, J, Eley, TC, Taylor, A, Hughes, C, Asherson, P, Caspi, A, Moffitt, TE (2004). Co-occurrence of ADHD and low IQ has genetic origins. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 124, 41–47.Google Scholar
Kuntsi, J, McLoughlin, G, Asherson, P (2006 a). Attention deficit hyperactivity disorder. Neuromolecular Medicine 8, 461–484.CrossRefGoogle ScholarPubMed
Kuntsi, J, Oosterlaan, J, Stevenson, J (2001). Psychological mechanisms in hyperactivity: I. Response inhibition deficit, working memory impairment, delay aversion, or something else? Journal of Child Psychology and Psychiatry 42, 199–210.CrossRefGoogle ScholarPubMed
Kuntsi, J, Rogers, H, Swinard, G, Borger, N, Meere, J, Rijsdijk, F, Asherson, P (2006 b). Reaction time, inhibition, working memory and ‘delay aversion’ performance: genetic influences and their interpretation. Psychological Medicine 36, 1613–1624.CrossRefGoogle ScholarPubMed
Kuntsi, J, Stevenson, J (2001). Psychological mechanisms in hyperactivity: II. The role of genetic factors. Journal of Child Psychology and Psychiatry 42, 211–219.CrossRefGoogle ScholarPubMed
Kuntsi, J, Wood, AC, Van Der Meere, J, Asherson, P (2009). Why cognitive performance in ADHD may not reveal true potential: findings from a large population-based sample. Journal of the International Neuropsychological Society 15, 570–579.CrossRefGoogle Scholar
Leth-Steensen, C, Elbaz, ZK, Douglas, VI (2000). Mean response times, variability, and skew in the responding of ADHD children: a response time distributional approach. Acta Psychologica (Amsterdam) 104, 167–190.CrossRefGoogle ScholarPubMed
Loehlin, JC (1996). The Cholesky approach: a cautionary note. Behavior Genetics 26, 65–69.CrossRefGoogle Scholar
Loo, SK, Smalley, SL (2008). Preliminary report of familial clustering of EEG measures in ADHD. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 147B, 107–109.CrossRefGoogle ScholarPubMed
Luciano, M, Wright, MJ, Geffen, GM, Geffen, LB, Smith, GA, Martin, NG (2004). A genetic investigation of the covariation among inspection time, choice reaction time, and IQ subtest scores. Behavior Genetics 34, 41–50.CrossRefGoogle ScholarPubMed
Neale, MC, Boker, SM, Xie, G, Maes, H (2006). Mx: Statistical Modeling. Department of Psychiatry, VCU Box 900126: Richmond, VA 23298.Google Scholar
Nigg, JT, Blaskey, LG, Stawicki, JA, Sachek, J (2004). Evaluating the endophenotype model of ADHD neuropsychological deficit: results for parents and siblings of children with ADHD combined and inattentive subtypes. Journal of Abnormal Psychology 113, 614–625.CrossRefGoogle ScholarPubMed
O'Connell, RG, Bellgrove, MA, Dockree, PM, Lau, A, Fitzgerald, M, Robertson, IH (2008). Self-Alert Training: volitional modulation of autonomic arousal improves sustained attention. Neuropsychologia 46, 1379–1390.CrossRefGoogle ScholarPubMed
Polderman, TJ, Gosso, MF, Posthuma, D, Van Beijsterveldt, TC, Heutink, P, Verhulst, FC, Boomsma, DI (2006). A longitudinal twin study on IQ, executive functioning, and attention problems during childhood and early adolescence. Acta Neurologica Belgica 106, 191–207.Google ScholarPubMed
Price, TS, Freeman, B, Craig, I, Petrill, SA, Ebersole, L, Plomin, R (2000). Infant zygosity can be assigned by parental report questionnaire data. Twin Research 3, 129–133.CrossRefGoogle ScholarPubMed
Rijsdijk, FV, Sham, PC (2002). Analytic approaches to twin data using structural equation models. Briefings in Bioinformatics 3, 119–133.CrossRefGoogle ScholarPubMed
Rommelse, NN (2008). Endophenotypes in the genetic research of ADHD over the last decade: have they lived up to their expectations? Expert Review of Neurotherapeutics 8, 1425–1429.CrossRefGoogle ScholarPubMed
Rommelse, NN, Altink, ME, Oosterlaan, J, Beem, L, Buschgens, CJ, Buitelaar, J, Sergeant, JA (2008). Speed, variability, and timing of motor output in ADHD: which measures are useful for endophenotypic research? Behavior Genetics 38, 121–132.Google Scholar
Sattler, JM (1992). Assessment of Children: WISC-III and WPPSI-R Supplement. Jerome M. Sattler: San Diego.Google Scholar
Sergeant, JA (2005). Modeling attention-deficit/hyperactivity disorder: a critical appraisal of the cognitive-energetic model. Biological Psychiatry 57, 1248–1255.CrossRefGoogle ScholarPubMed
Spinath, FM, O'Connor, TG (2003). A behavioral genetic study of the overlap between personality and parenting. Journal of Personality 71, 785–808.CrossRefGoogle ScholarPubMed
Trouton, A, Spinath, FM, Plomin, R (2002). Twins early development study (TEDS): a multivariate, longitudinal genetic investigation of language, cognition and behavior problems in childhood. Twin Research 5, 444–448.CrossRefGoogle ScholarPubMed
van der Meere, J (1996). The role of attention. In Hyperactivity Disorders of Childhood. Cambridge Monographs in Child and Adolescent Psychiatry (ed. Sandberg, S. T.), pp. 109–146. Cambridge University Press: Cambridge.Google Scholar
van der Meere, JJ (2002). The role of attention. In Hyperactivity Disorders of Childhood. Cambridge Monographs in Child and Adolescent Psychiatry (ed. Sandberg, S.), pp. 162–298. Cambridge University Press: Cambridge.Google Scholar
van der Meere, J, Stemerdink, N, Gunning, B (1995). Effects of presentation rate of stimuli on response inhibition in ADHD children with and without tics. Perceptual and Motor Skills 81, 259–262.CrossRefGoogle ScholarPubMed
Wechsler, D (1991). Intelligence Scale for Children. The Psychological Corporation: London.Google Scholar