Hostname: page-component-cd9895bd7-dzt6s Total loading time: 0 Render date: 2024-12-13T00:41:10.118Z Has data issue: false hasContentIssue false
  • English
  • Français

The relationship between ADHD and key cognitive phenotypes is not mediated by shared familial effects with IQ

Published online by Cambridge University Press:  04 June 2010

A. C. Wood ,
F. Rijsdijk ,
K. A. Johnson ,
P. Andreou ,
B. Albrecht ,
A. Arias-Vasquez ,
J. K. Buitelaar ,
G. McLoughlin ,
N. N. J. Rommelse  and
J. A. Sergeant
...Show all authors
A. C. Wood*
Affiliation:
MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, UK Department of Epidemiology and Section on Statistical Genetics, University of Alabama at Birmingham, Birmingham, AL, USA
F. Rijsdijk
Affiliation:
MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, UK
K. A. Johnson
Affiliation:
Department of Psychiatry, Trinity Centre for Health Sciences, St James's Hospital, Dublin, Ireland School of Psychology, Queen's University Belfast, Northern Ireland, UK
P. Andreou
Affiliation:
MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, UK
B. Albrecht
Affiliation:
Child and Adolescent Psychiatry, University of Göttingen, Germany
A. Arias-Vasquez
Affiliation:
Department of Psychiatry, Donders Institute for Brain, Cognition and Behavior, Centre for Neuroscience, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands Department of Human Genetics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
J. K. Buitelaar
Affiliation:
Department of Psychiatry, Donders Institute for Brain, Cognition and Behavior, Centre for Neuroscience, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
G. McLoughlin
Affiliation:
MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, UK
N. N. J. Rommelse
Affiliation:
Department of Psychiatry, Donders Institute for Brain, Cognition and Behavior, Centre for Neuroscience, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
J. A. Sergeant
Affiliation:
Department of Clinical Neuropsychology, Vrije Universiteit, Amsterdam, The Netherlands
E. J. S. Sonuga-Barke
Affiliation:
Developmental Brain-Behaviour Laboratory, University of Southampton, UK Department of Experimental Clinical and Health Psychology, Ghent University, Belgium
H. Uebel
Affiliation:
Child and Adolescent Psychiatry, University of Göttingen, Germany
J. J. van der Meere
Affiliation:
Department of Neuropsychology, University of Groningen, The Netherlands
T. Banaschewski
Affiliation:
Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany
M. Gill
Affiliation:
Department of Psychiatry, Trinity Centre for Health Sciences, St James's Hospital, Dublin, Ireland
I. Manor
Affiliation:
S. Herzog Memorial Hospital, Research Department, Jerusalem, Israel
A. Miranda
Affiliation:
Department of Developmental and Educational Psychology, University of Valencia, Spain
F. Mulas
Affiliation:
Department of Neuropediatrics, La Fe University Hospital, Valencia, Spain
R. D. Oades
Affiliation:
Clinic for Child and Adolescent Psychiatry and Psychotherapy, University of Duisburg-Essen, Germany
H. Roeyers
Affiliation:
Department of Experimental Clinical and Health Psychology, Ghent University, Belgium
A. Rothenberger
Affiliation:
Child and Adolescent Psychiatry, University of Göttingen, Germany
H. C. Steinhausen
Affiliation:
Department of Child and Adolescent Psychiatry, University of Zurich, Switzerland Child and Adolescent Clinical Psychology, Institute of Psychology, University of Basel, Switzerland Child and Adolescent Psychiatry, Psychiatric Hospital Aalborg, University Hospital Aarhus, Aalborg, Denmark
S. V. Faraone
Affiliation:
Department of Neuroscience, SUNY Upstate Medical University, Syracuse, NY, USA Department of Psychiatry, SUNY Upstate Medical University, Syracuse, NY, USA
P. Asherson
Affiliation:
MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, UK
J. Kuntsi
Affiliation:
MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, UK
*
*Address for correspondence: Dr A. C. Wood, RPHB 230P, 1530 3rd Avenue South, Birmingham, AL 35294-0022, USA. (Email: lekki.wood@googlemail.com)
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Twin and sibling studies have identified specific cognitive phenotypes that may mediate the association between genes and the clinical symptoms of attention deficit hyperactivity disorder (ADHD). ADHD is also associated with lower IQ scores. We aimed to investigate whether the familial association between measures of cognitive performance and the clinical diagnosis of ADHD is mediated through shared familial influences with IQ.

Method

Multivariate familial models were run on data from 1265 individuals aged 6–18 years, comprising 920 participants from ADHD sibling pairs and 345 control participants. Cognitive assessments included a four-choice reaction time (RT) task, a go/no-go task, a choice–delay task and an IQ assessment. The analyses focused on the cognitive variables of mean RT (MRT), RT variability (RTV), commission errors (CE), omission errors (OE) and choice impulsivity (CI).

Results

Significant familial association (rF) was confirmed between cognitive performance and both ADHD (rF=0.41–0.71) and IQ (rF=−0.25 to −0.49). The association between ADHD and cognitive performance was largely independent (80–87%) of any contribution from etiological factors shared with IQ. The exception was for CI, where 49% of the overlap could be accounted for by the familial variance underlying IQ.

Conclusions

The aetiological factors underlying lower IQ in ADHD seem to be distinct from those between ADHD and RT/error measures. This suggests that lower IQ does not account for the key cognitive impairments observed in ADHD. The results have implications for molecular genetic studies designed to identify genes involved in ADHD.

Keywords

ADHDcognitiveheritabilityIQintermediate phenotype
Type
Original Articles
Information
Psychological Medicine , Volume 41 , Issue 4 , April 2011 , pp. 861 - 871
Copyright
Copyright © Cambridge University Press 2010

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.CrossRefGoogle ScholarPubMed
Asherson, P, Zhou, K, Anney, RJ, Franke, B, Buitelaar, J, Ebstein, R, Gill, M, Altink, M, Arnold, R, Boer, F, Brookes, K, Buschgens, C, Butler, L, Cambell, D, Chen, W, Christiansen, H, Feldman, L, Fleischman, K, Fliers, E, Howe-Forbes, R, Goldfarb, A, Heise, A, Gabriels, I, Johansson, L, Lubetzki, I, Marco, R, Medad, S, Minderaa, R, Mulas, F, Muller, U, Mulligan, A, Neale, B, Rijsdijk, F, Rabin, K, Rommelse, N, Sethna, V, Sorohan, J, Uebel, H, Psychogiou, L, Weeks, A, Barrett, R, Xu, X, Banaschewski, T, Sonuga-Barke, E, Eisenberg, J, Manor, I, Miranda, A, Oades, RD, Roeyers, H, Rothenberger, A, Sergeant, J, Steinhausen, HC, Taylor, E, Thompson, M, Faraone, SV (2008). A high-density SNP linkage scan with 142 combined subtype ADHD sib pairs identifies linkage regions on chromosomes 9 and 16. Molecular Psychiatry 13, 514–521.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
Bitsakou, P, Psychogiou, L, Thompson, M, Sonuga-Barke, EJ (2009). Delay aversion in attention deficit/hyperactivity disorder: an empirical investigation of the broader phenotype. Neuropsychologia 47, 446–456.CrossRefGoogle ScholarPubMed
Borger, N, van der Meere, JJ (2000). Motor control and state regulation in children with ADHD: a cardiac response study. Biological Psychology 51, 247–267.CrossRefGoogle ScholarPubMed
Burt, SA (2009). Rethinking environmental contributions to child and adolescent psychopathology: a meta-analysis of shared environmental influences. Psychological Bulletin 135, 608–637.CrossRefGoogle ScholarPubMed
Chen, W, Zhou, K, Sham, P, Franke, B, Kuntsi, J, Campbell, D, Fleischman, K, Knight, J, Andreou, P, Arnold, R, Altink, M, Boer, F, Boholst, MJ, Buschgens, C, Butler, L, Christiansen, H, Fliers, E, Howe-Forbes, R, Gabriels, I, Heise, A, Korn-Lubetzki, I, Marco, R, Medad, S, Minderaa, R, Muller, UC, Mulligan, A, Psychogiou, L, Rommelse, N, Sethna, V, Uebel, H, McGuffin, P, Plomin, R, Banaschewski, T, Buitelaar, J, Ebstein, R, Eisenberg, J, Gill, M, Manor, I, Miranda, A, Mulas, F, Oades, RD, Roeyers, H, Rothenberger, A, Sergeant, J, Sonuga-Barke, E, Steinhausen, HC, Taylor, E, Thompson, M, Faraone, SV, Asherson, P (2008). DSM-IV combined type ADHD shows familial association with sibling trait scores: a sampling strategy for QTL linkage. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics 147B, 1450–1460.CrossRefGoogle ScholarPubMed
Conners, CK, Sitarenios, G, Parker, JD, Epstein, JN (1998). 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
Gottesman, II, Gould, TD (2003). The endophenotype concept in psychiatry: etymology and strategic intentions. American Journal of Psychiatry 160, 636–645.CrossRefGoogle ScholarPubMed
Gottesman, II, Shields, J (1973). Genetic theorizing and schizophrenia. British Journal of Psychiatry 122, 15–30.CrossRefGoogle ScholarPubMed
Halperin, JM, Schulz, KP (2006). Revisiting the role of the prefrontal cortex in the pathophysiology of attention-deficit/hyperactivity disorder. Psychological Bulletin 132, 560–581.CrossRefGoogle ScholarPubMed
Halperin, JM, Trampush, JW, Miller, CJ, Marks, DJ, Newcorn, JH (2008). Neuropsychological outcome in adolescents/young adults with childhood ADHD: profiles of persisters, remitters and controls. Journal of Child Psychology and Psychiatry and Allied Disciplines 49, 958–966.CrossRefGoogle ScholarPubMed
Jester, JM, Nigg, JT, Puttler, LI, Long, JC, Fitzgerald, HE, Zucker, RA (2009). Intergenerational transmission of neuropsychological executive functioning. Brain and Cognition 70, 145–153.CrossRefGoogle ScholarPubMed
Johnson, KA, Barry, E, Bellgrove, MA, Cox, M, Kelly, SP, Dáibhis, A, Daly, M, Keavey, M, Watchorn, A, Fitzgerald, M, McNicholas, F, Kirley, A, Robertson, IH, Gill, M (2008). Dissociation in response to methylphenidate on response variability in a group of medication naïve children with ADHD. Neuropsychologia 46, 1532–1541.CrossRefGoogle Scholar
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? Behavior and Brain Functioning 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 124B, 41–47.CrossRefGoogle ScholarPubMed
Kuntsi, J, Rogers, H, Swinard, G, Borger, N, van der Meere, J, Rijsdijk, F, Asherson, P (2006). Reaction time, inhibition, working memory and ‘delay aversion’ performance: genetic influences and their interpretation. Psychological Medicine 36, 1613–1624.CrossRefGoogle ScholarPubMed
Kuntsi, J, Wood, AC, Rijsdijk, F, Andreou, P, Christiansen, H, Gabriels, I, Marco, R, Meidad, S, Mueller, U, Mulligan, A, Uebel, H, van der Meere, JJ, Banaschewski, T, Gill, M, Manor, I, Miranda, A, Mulas, F, Oades, R, Roeyers, H, Rothenberger, A, Steinhausen, HC, Faraone, S, Asherson, P (in press). The independent vs. shared etiology of cognitive process associated with ADHD: multivariate model fitting to large samples of ADHD and control sibling pairs. Archives of General Psychiatry.Google Scholar
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
Loo, SK, Hale, TS, Macion, J, Hanada, G, McGough, J, McCracken, JT, Smalley, SL (2009). Cortical activity patterns in ADHD during arousal, activation and sustained attention. Neuropsychologia 47, 2114–2119.CrossRefGoogle ScholarPubMed
Marco, R, Miranda, A, Schlotz, W, Melia, A, Mulligan, A, Muller, U, Andreou, P, Butler, L, Christiansen, H, Gabriels, I, Medad, S, Albrecht, B, Uebel, H, Asherson, P, Banaschewski, T, Gill, M, Kuntsi, J, Mulas, F, Oades, R, Roeyers, H, Steinhausen, HC, Rothenberger, A, Faraone, SV, Sonuga-Barke, EJ (2009). Delay and reward choice in ADHD: an experimental test of the role of delay aversion. Neuropsychology 23, 367–380.CrossRefGoogle ScholarPubMed
Neale, MC, Boker, S, Xie, G, Maes, H (2006). Mx: Statistical Modeling. Department of Psychiatry, Medical College of Virginia: Richmond, VA.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
Paloyelis, Y, Asherson, P, Kuntsi, J (2009). Are ADHD symptoms associated with delay aversion or choice impulsivity? A general population study. Journal of the American Academy of Child and Adolescent Psychiatry 48, 837–846.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
Rijsdijk, FV, van Haren, NEM, Picchioni, M, McDonald, C, Toulopoulou, T, Hulshoff Pol, HE, Kahn, RS, Murray, R, Sham, P (2005). Brain MRI abnormalities in schizophrenia: same genes or same environment? Psychological Medicine 35, 1399–1409.CrossRefGoogle ScholarPubMed
Rommelse, NN (2008). Endophenotypes in the genetic research of ADHD over the last decade: have they lived up to their expectations? Expert Reviews in Neurotherapy 8, 1425–1429.CrossRefGoogle ScholarPubMed
Rommelse, NN, Altink, ME, Oosterlaan, J, Buschgens, CJ, Buitelaar, J, Sergeant, JA (2008). Support for an independent familial segregation of executive and intelligence endophenotypes in ADHD families. Psychological Medicine 38, 1595–1606.CrossRefGoogle ScholarPubMed
Sattler, JM (1992). Assessment of Children. WISC-III and WPPSI-R Supplement. Jerome M. Sattler Publishing, Inc.: San Diego, CA.Google Scholar
Schachar, RJ, Crosbie, J, Barr, CL, Ornstein, TJ, Kennedy, J, Malone, M, Roberts, W, Ickowicz, A, Tannock, R, Chen, S, Pathare, T (2005). Inhibition of motor responses in siblings concordant and discordant for attention deficit hyperactivity disorder. American Journal of Psychiatry 162, 1076–1082.CrossRefGoogle ScholarPubMed
Slaats-Willemse, D, Swaab-Barneveld, H, de Sonneville, L, van der Meulen, E, Buitelaar, J (2003). Deficient response inhibition as a cognitive endophenotype of ADHD. Journal of the American Academy of Child and Adolescent Psychiatry 42, 1242–1248.CrossRefGoogle ScholarPubMed
Sonuga-Barke, EJS (2005). Causal models of ADHD: from simple single deficits to multiple developmental pathways. Biological Psychiatry 57, 1231–1238.CrossRefGoogle Scholar
Taylor, E, Everitt, B, Thorley, G, Schachar, R, Rutter, M, Wieselberg, M (1986). Conduct disorder and hyperactivity: II. A cluster analytic approach to the identification of a behavioural syndrome. British Journal of Psychiatry 149, 768–777.CrossRefGoogle Scholar
Uebel, H, Albrecht, B, Asherson, P, Borger, NA, van der Meere, JJ, Butler, L, Chen, W, Christiansen, H, Heise, A, Kuntsi, J (2010). Performance variability, impulsivity errors and the impact of incentives as gender-independent endophenotypes for ADHD. Journal of Child Psychology and Psychiatry, and Allied Disciplines 51, 210–218.CrossRefGoogle ScholarPubMed
Waldman, ID, Nigg, JT, Gizer, IR, Park, L, Rappley, MD, Friderici, K (2006). The adrenergic receptor alpha-2A gene (ADRA2A) and neuropsychological executive functions as putative endophenotypes for childhood ADHD. Cognitive, Affective and Behavioral Neuroscience 6, 18–30.CrossRefGoogle ScholarPubMed
Wechsler, D (1991). Wechsler Intelligence Scale for Children. Psychological Corporation: San Antonio, TX.Google Scholar
Wechsler, D (1997). WAIS III: Wechsler Adult Intelligence Scale, 3rd edn. The Psychological Corporation: San Antonio, TX.Google Scholar
Willcutt, EG, Doyle, AE, Nigg, JT, Faraone, SV, Pennington, BF (2005). Validity of the executive function theory of attention-deficit/hyperactivity disorder: a meta-analytic review. Biological Psychiatry 57, 1336–1346.CrossRefGoogle ScholarPubMed
Wood, AC, Asherson, P, Rijsdijk, F, Kuntsi, J (2009 a). Is overactivity a core feature in ADHD? Familial and receiver operating characteristic curve analysis of mechanically assessed activity level. Journal of the American Academy of Child and Adolescent Psychiatry 48, 1023–1030.CrossRefGoogle ScholarPubMed
Wood, AC, Asherson, P, van der Meere, JJ, Kuntsi, J (2009 b). Separation of genetic influences on attention deficit hyperactivity disorder symptoms and reaction time performance from those on IQ. Psychological Medicine. Published online: 15 September 2009. doi:10.1017/S003329170999119X.Google ScholarPubMed