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

  • A. C. Wood (a1) (a2), F. Rijsdijk (a1), K. A. Johnson (a3) (a4), P. Andreou (a1), B. Albrecht (a5), A. Arias-Vasquez (a6) (a7), J. K. Buitelaar (a6), G. McLoughlin (a1), N. N. J. Rommelse (a6), J. A. Sergeant (a8), E. J. S. Sonuga-Barke (a9) (a10), H. Uebel (a5), J. J. van der Meere (a11), T. Banaschewski (a12), M. Gill (a3), I. Manor (a13), A. Miranda (a14), F. Mulas (a15), R. D. Oades (a16), H. Roeyers (a10), A. Rothenberger (a5), H. C. Steinhausen (a17) (a18) (a19), S. V. Faraone (a20) (a21), P. Asherson (a1) and J. Kuntsi (a1)...
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.

Copyright
Corresponding author
*Address for correspondence: Dr A. C. Wood, RPHB 230P, 1530 3rd Avenue South, Birmingham, AL 35294-0022, USA. (Email: lekki.wood@googlemail.com)
References
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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, 17031715.
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, 514521.
Bidwell LC, Willcutt EG, Defries JC, Pennington BF (2007). Testing for neuropsychological endophenotypes in siblings discordant for attention-deficit/hyperactivity disorder. Biological Psychiatry 62, 991998.
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, 446456.
Borger N, van der Meere JJ (2000). Motor control and state regulation in children with ADHD: a cardiac response study. Biological Psychology 51, 247267.
Burt SA (2009). Rethinking environmental contributions to child and adolescent psychopathology: a meta-analysis of shared environmental influences. Psychological Bulletin 135, 608637.
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, 14501460.
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, 279291.
Gottesman II, Gould TD (2003). The endophenotype concept in psychiatry: etymology and strategic intentions. American Journal of Psychiatry 160, 636645.
Gottesman II, Shields J (1973). Genetic theorizing and schizophrenia. British Journal of Psychiatry 122, 1530.
Halperin JM, Schulz KP (2006). Revisiting the role of the prefrontal cortex in the pathophysiology of attention-deficit/hyperactivity disorder. Psychological Bulletin 132, 560581.
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, 958966.
Jester JM, Nigg JT, Puttler LI, Long JC, Fitzgerald HE, Zucker RA (2009). Intergenerational transmission of neuropsychological executive functioning. Brain and Cognition 70, 145153.
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, 15321541.
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, 630638.
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.
Klein C, Wendling K, Huettner P, Ruder H, Peper M (2006). Intra-subject variability in attention-deficit hyperactivity disorder. Biological Psychiatry 60, 10881097.
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.
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, 4147.
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, 16131624.
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.
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, 570579.
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, 21142119.
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, 367380.
Neale MC, Boker S, Xie G, Maes H (2006). Mx: Statistical Modeling. Department of Psychiatry, Medical College of Virginia: Richmond, VA.
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, 614625.
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, 13791390.
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, 837846.
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, 191207.
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, 13991409.
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, 14251429.
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, 15951606.
Sattler JM (1992). Assessment of Children. WISC-III and WPPSI-R Supplement. Jerome M. Sattler Publishing, Inc.: San Diego, CA.
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, 10761082.
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, 12421248.
Sonuga-Barke EJS (2005). Causal models of ADHD: from simple single deficits to multiple developmental pathways. Biological Psychiatry 57, 12311238.
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, 768777.
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, 210218.
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, 1830.
Wechsler D (1991). Wechsler Intelligence Scale for Children. Psychological Corporation: San Antonio, TX.
Wechsler D (1997). WAIS III: Wechsler Adult Intelligence Scale, 3rd edn. The Psychological Corporation: San Antonio, TX.
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, 13361346.
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, 10231030.
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.
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