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Attention deficit hyperactivity disorder (ADHD) and executive functioning in affected and unaffected adolescents and their parents: challenging the endophenotype construct

Published online by Cambridge University Press:  31 May 2013

A. J. A. M. Thissen ,
N. N. J. Rommelse ,
P. J. Hoekstra ,
C. Hartman ,
D. Heslenfeld ,
M. Luman ,
M. van Lieshout ,
B. Franke ,
J. Oosterlaan  and
J. K. Buitelaar
A. J. A. M. Thissen*
Affiliation:
Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, The Netherlands Karakter Child and Adolescent Psychiatry University Centre, Nijmegen, The Netherlands
N. N. J. Rommelse
Affiliation:
Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, The Netherlands Karakter Child and Adolescent Psychiatry University Centre, Nijmegen, The Netherlands
P. J. Hoekstra
Affiliation:
Department of Psychiatry, University Medical Centre Groningen, University of Groningen, The Netherlands
C. Hartman
Affiliation:
Department of Psychiatry, University Medical Centre Groningen, University of Groningen, The Netherlands
D. Heslenfeld
Affiliation:
VU University, Amsterdam, The Netherlands
M. Luman
Affiliation:
VU University, Amsterdam, The Netherlands
M. van Lieshout
Affiliation:
VU University, Amsterdam, The Netherlands
B. Franke
Affiliation:
Departments of Human Genetics and Psychiatry, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
J. Oosterlaan
Affiliation:
VU University, Amsterdam, The Netherlands
J. K. Buitelaar
Affiliation:
Karakter Child and Adolescent Psychiatry University Centre, Nijmegen, The Netherlands Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, The Netherlands
*
* Address for correspondence: Ms. A. J. A. M. Thissen, Reinier Postlaan 12, 6525 GC Nijmegen, The Netherlands. (Email: A.Thissen@psy.umcn.nl)
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Abstract

Background

The results of twin and sibling studies suggest that executive functioning is a prime candidate endophenotype in attention deficit hyperactivity disorder (ADHD). However, studies have not assessed the co-segregation of executive function (EF) deficits from parents to offspring directly, and it is unclear whether executive functioning is an ADHD endophenotype in adolescents, given the substantial changes in prefrontal lobe functioning, EF and ADHD symptoms during adolescence.

Method

We recruited 259 ADHD and 98 control families with an offspring average age of 17.3 years. All participants were assessed for ADHD and EF [inhibition, verbal (VWM) and visuospatial working memory (VsWM)]. Data were analysed using generalized estimating equations (GEEs).

Results

Parental ADHD was associated with offspring ADHD and parental EF was associated with offspring EF but there were no cross-associations (parental ADHD was not associated with offspring EF or vice versa). Similar results were found when siblings were compared. EF deficits were only found in affected adolescents and not in their unaffected siblings or (un)affected parents.

Conclusions

The core EFs proposed to be aetiologically related to ADHD, that is working memory and inhibition, seem to be aetiologically independent of ADHD in adolescence. EF deficits documented in childhood in unaffected siblings were no longer present in adolescence, suggesting that children ‘grow out’ of early EF deficits. This is the first study to document ADHD and EF in a large family sample with adolescent offspring. The results suggest that, after childhood, the majority of influences on ADHD are independent from those on EF. This has potential implications for current aetiological models of causality in ADHD.

Keywords

ADHDadolescentsendophenotypeexecutive functioning
Type
Original Articles
Information
Psychological Medicine , Volume 44 , Issue 4 , March 2014 , pp. 881 - 892
Copyright
Copyright © Cambridge University Press 2013 

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References

APA (2000). Diagnostic and Statistical Manual of Mental Disorders, 4th edn, text revision (DSM-IV-TR). American Psychiatric Association: Washington, DC.Google Scholar
Best, JR, Miller, PH, Jones, LL (2009). Executive functions after age 5: changes and correlates. Developmental Review 29, 180–200.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.Google Scholar
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
Blakemore, SJ, Choudhury, S (2006). Development of the adolescent brain: implications for executive function and social cognition. Journal of Child Psychology and Psychiatry 47, 296–312.Google Scholar
Boomsma, DI, Saviouk, V, Hottenga, JJ, Distel, MA, de Moor, MH, Vink, JM, Geels, LM, van Beek, JH, Bartels, M, de Geus, EJ, Willemsen, G (2010). Genetic epidemiology of attention deficit hyperactivity disorder (ADHD index) in adults. PLoS One 5, e10621.Google Scholar
Boonstra, AM, Oosterlaan, J, Sergeant, JA, Buitelaar, JK (2005). Executive functioning in adult ADHD: a meta-analytic review. Psychological Medicine 35, 1097–1108.Google Scholar
Coghill, D, Nigg, J, Rothenberger, A, Sonuga-Barke, E, Tannock, R (2005). Whither causal models in the neuroscience of ADHD? Developmental Science 8, 105–114.Google Scholar
Conners, CK, Erhardt, D, Sparrow, EP (1999). Conners’ Adult ADHD Rating Scales: CAARS. Multi-Health Systems: North Tonawanda, NY.Google Scholar
Crosbie, J, Arnold, P, Paterson, A, Swanson, J, Dupuis, A, Li, X, Shan, J, Goodale, T, Tam, C, Strug, LJ, Schachar, RJ (2013). Response inhibition and ADHD traits: correlates and heritability in a community sample. Journal of Abnormal Child Psychology 41, 497–507.CrossRefGoogle Scholar
Cummins, TD, Hawi, Z, Hocking, J, Strudwick, M, Hester, R, Garavan, H, Wagner, J, Chambers, CD, Bellgrove, MA (2012). Dopamine transporter genotype predicts behavioural and neural measures of response inhibition. Molecular Psychiatry 17, 1086–1092.CrossRefGoogle ScholarPubMed
De Luca, CR, Wood, SJ, Anderson, V, Buchanan, JA, Proffitt, TM, Mahony, K, Pantelis, C (2003). Normative data from the CANTAB. I: Development of executive function over the lifespan. Journal of Clinical and Experimental Neuropsychology 25, 242–254.Google Scholar
Dumontheil, I, Klingberg, T (2012). Brain activity during a visuospatial working memory task predicts arithmetical performance 2 years later. Cerebral Cortex 22, 1078–1085.Google Scholar
Durston, S, Tottenham, NT, Thomas, KM, Davidson, MC, Eigsti, IM, Yang, Y, Ulug, AM, Casey, BJ (2003). Differential patterns of striatal activation in young children with and without ADHD. Biological Psychiatry 53, 871–878.Google Scholar
Fair, DA, Bathula, D, Nikolas, MA, Nigg, JT (2012). Distinct neuropsychological subgroups in typically developing youth inform heterogeneity in children with ADHD. Proceedings of the National Academy of Sciences USA 109, 6769–6774.CrossRefGoogle ScholarPubMed
Gilsbach, S, Neufang, S, Scherag, S, Vloet, TD, Fink, GR, Herpertz-Dahlmann, B, Konrad, K (2012). Effects of the DRD4 genotype on neural networks associated with executive functions in children and adolescents. Developmental Cognitive Neuroscience 2, 417–427.Google Scholar
Goos, LM, Crosbie, J, Payne, S, Schachar, R (2009). Validation and extension of the endophenotype model in ADHD patterns of inheritance in a family study of inhibitory control. American Journal of Psychiatry 166, 711–717.CrossRefGoogle Scholar
Greven, CU, Asherson, P, Rijsdijk, FV, Plomin, R (2011). A longitudinal twin study on the association between inattentive and hyperactive-impulsive ADHD symptoms. Journal of Abnormal Child Psychology 39, 623–632.Google Scholar
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 49, 958–966.Google Scholar
Hervey, AS, Epstein, JN, Curry, JF (2004). Neuropsychology of adults with attention-deficit/hyperactivity disorder: a meta-analytic review. Neuropsychology 18, 485–503.Google Scholar
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.Google Scholar
Johnson, MH (2012). Executive function and developmental disorders: the flip side of the coin. Trends in Cognitive Sciences 16, 454–457.Google Scholar
Kasper, LJ, Alderson, RM, Hudec, KL (2012). Moderators of working memory deficits in children with attention-deficit/hyperactivity disorder (ADHD): a meta-analytic review. Clinical Psychology Review 32, 605–617.CrossRefGoogle ScholarPubMed
Kaufman, J, Birmaher, B, Brent, D, Rao, U, Flynn, C, Moreci, P, Williamson, D, Ryan, N (1997). Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL): initial reliability and validity data. Journal of the American Academy of Child and Adolescent Psychiatry 36, 980–988.Google Scholar
Klingberg, T, Forssberg, H, Westerberg, H (2002). Training of working memory in children with ADHD. Journal of Clinical and Experimental Neuropsychology 24, 781–791.Google Scholar
Kooij, JJ, Buitelaar, JK, van den Oord, EJ, Furer, JW, Rijnders, CA, Hodiamont, PP (2005). Internal and external validity of attention-deficit hyperactivity disorder in a population-based sample of adults. Psychological Medicine 35, 817–827.Google Scholar
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
Leon-Carrion, J, Garcia-Orza, J, Perez-Santamaria, FJ (2004). Development of the inhibitory component of the executive functions in children and adolescents. International Journal of Neuroscience 114, 1291–1311.Google Scholar
Lijffijt, M, Kenemans, JL, Verbaten, MN, van Engeland, H (2005). A meta-analytic review of stopping performance in attention-deficit/hyperactivity disorder: deficient inhibitory motor control? Journal of Abnormal Psychology 114, 216–222.Google Scholar
Logan, GD, Cowan, WB, Davis, KA (1984). On the ability to inhibit simple and choice reaction time responses: a model and a method. Journal of Experimental Psychology. Human Perception and Performance 10, 276–291.Google Scholar
Luciana, M, Conklin, HM, Hooper, CJ, Yarger, RS (2005). The development of nonverbal working memory and executive control processes in adolescents. Child Development 76, 697–712.CrossRefGoogle ScholarPubMed
Luna, B, Garver, KE, Urban, TA, Lazar, NA, Sweeney, JA (2004). Maturation of cognitive processes from late childhood to adulthood. Child Development 75, 1357–1372.Google Scholar
Martinussen, R, Hayden, J, Hogg-Johnson, S, Tannock, R (2005). A meta-analysis of working memory impairments in children with attention-deficit/hyperactivity disorder. Journal of the American Academy of Child and Adolescent Psychiatry 44, 377–384.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.Google Scholar
Nigg, JT, Willcutt, EG, Doyle, AE, Sonuga-Barke, EJS (2005). Causal heterogeneity in attention-deficit/hyperactivity disorder: do we need neuropsychologically impaired subtypes? Biological Psychiatry 57, 1224–1230.Google Scholar
Nijmeijer, JS, Hoekstra, P, Minderaa, R, Buitelaar, J, Altink, M, Buschgens, CJM, Fliers, E, Rommelse, NNJ, Sergeant, J, Hartman, CA (2009). PDD symptoms in ADHD, an independent familial trait? Journal of Abnormal Child Psychology 37, 443–453.Google Scholar
Preacher, KJ, Hayes, AF (2004). SPSS and SAS procedures for estimating indirect effects in simple mediation models. Behaviour Research Methods, Instruments, and Computers 36, 717–731.Google Scholar
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.Google Scholar
Rommelse, NNJ, Altink, ME, Oosterlaan, J, Buschgens, CJM, Buitelaar, J, Sergeant, JA (2008). Support for an independent familial segregation of executive and intelligence endophenotypes in ADHD families. Psychological Medicine 38, 1595–1606.Google Scholar
Rubia, K, Russell, T, Overmeyer, S, Brammer, MJ, Bullmore, ET, Sharma, T, Simmons, A, Williams, SCR, Giampietro, V, Andrew, CM, Taylor, E (2001). Mapping motor inhibition: conjunctive brain activations across different versions of go/no-go and stop tasks. NeuroImage 13, 250–261.Google Scholar
Rubia, K, Smith, AB, Brammer, MJ, Taylor, E (2003). Right inferior prefrontal cortex mediates response inhibition while mesial prefrontal cortex is responsible for error detection. NeuroImage 20, 351–358.Google Scholar
Rutter, M, Moffitt, TE, Caspi, A (2006). Gene-environment interplay and psychopathology: multiple varieties but real effects. Journal of Child Psychology and Psychiatry 47, 226–261.Google Scholar
Seidman, LJ, Biederman, J, Monuteaux, MC, Valera, E, Doyle, AE, Faraone, SV (2005). Impact of gender and age on executive functioning: do girls and boys with and without attention deficit hyperactivity disorder differ neuropsychologically in preteen and teenage years? Developmental Neuropsychology 27, 79–105.Google Scholar
Shaw, P, Eckstrand, K, Sharp, W, Blumenthal, J, Lerch, JP, Greenstein, D, Clasen, L, Evans, A, Giedd, J, Rapoport, JL (2007). Attention-deficit/hyperactivity disorder is characterized by a delay in cortical maturation. Proceedings of the National Academy of Sciences USA 104, 19649–19654.Google Scholar
Silverstein, AB (1975). Validity of WISC-R short forms. Journal of Clinical Psychology 31, 696–697.Google Scholar
Silverstein, AB (1982). 2-Subtest and 4-subtest short forms of the Wechsler Adult Intelligence Scale-Revised. Journal of Consulting and Clinical Psychology 50, 415–418.Google Scholar
Thissen, AJ, Rommelse, NN, Altink, ME, Oosterlaan, J, Buitelaar, JK (2012). Parent-of-origin effects in ADHD: distinct influences of paternal and maternal ADHD on neuropsychological functioning in offspring. Journal of Attention Disorders. Published online: 24 May 2012 . doi: 10.1177/1087054712443159.Google ScholarPubMed
Torralva, T, Gleichgerrcht, E, Lischinsky, A, Roca, M, Manes, F (2013). ‘Ecological’ and highly demanding executive tasks detect real-life deficits in high-functioning adult ADHD patients. Journal of Attention Disorders 17, 11–19.Google Scholar
van Ewijk, H, Heslenfeld, DJ, Luman, M, Rommelse, NN, Hartman, CA, Hoekstra, P, Franke, B, Buitelaar, JK, Oosterlaan, J (2013). Visuospatial working memory in ADHD patients, unaffected siblings, and healthy controls. Journal of Attention Disorders. Published online: 8 April 2013 . doi: 10.1177/1087054713482582.Google Scholar
van Lieshout, M, Luman, M, Buitelaar, J, Rommelse, NN, Oosterlaan, J (2013). Does neurocognitive functioning predict future or persistence of ADHD? A systematic review. Clinical Psychology Review 33, 539–560.Google Scholar
van Steijn, DJ, Richards, JS, Oerlemans, AM, de Ruiter, SW, van Aken, MA, Franke, B, Buitelaar, JK, Rommelse, NN (2012). The co-occurrence of autism spectrum disorder and attention-deficit/hyperactivity disorder symptoms in parents of children with ASD or ASD with ADHD. Journal of Child Psychology and Psychiatry 53, 954–963.Google Scholar
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.Google Scholar
Walters, JT, Owen, MJ (2007). Endophenotypes in psychiatric genetics. Molecular Psychiatry 12, 886–890.Google Scholar
Wechsler, D (2000). WAIS-III Nederlandstalige bewerking. Technische Handleiding . The Psychological Corporation: London.Google Scholar
Wechsler, D (2002). WISC-III Handleiding. The Psychological Corporation: London.Google Scholar
Welsh, MC, Pennington, BF (1988). Assessing frontal-lobe functioning in children: views from developmental psychology. Developmental Neuropsychology 4, 199–230.Google Scholar
Westerberg, H, Hirvikoski, T, Forssberg, H, Klingberg, T (2004). Visuo-spatial working memory span: a sensitive measure of cognitive deficits in children with ADHD. Child Neuropsychology 10, 155–161.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.Google Scholar
Woods, SP, Lovejoy, DW, Ball, JD (2002). Neuropsychological characteristics of adults with ADHD: a comprehensive review of initial studies. Clinical Neuropsychologist 16, 12–34.Google Scholar