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Support for an independent familial segregation of executive and intelligence endophenotypes in ADHD families

Published online by Cambridge University Press:  08 February 2008

N. N. J. Rommelse ,
M. E. Altink ,
J. Oosterlaan ,
C. J. M. Buschgens ,
J. Buitelaar  and
J. A. Sergeant
N. N. J. Rommelse*
Affiliation:
Department of Clinical Neuropsychology, VU University Amsterdam, Amsterdam, The Netherlands
M. E. Altink
Affiliation:
Department of Psychiatry, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
J. Oosterlaan
Affiliation:
Department of Clinical Neuropsychology, VU University Amsterdam, Amsterdam, The Netherlands
C. J. M. Buschgens
Affiliation:
Department of Psychiatry, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
J. Buitelaar
Affiliation:
Department of Psychiatry, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
J. A. Sergeant
Affiliation:
Department of Clinical Neuropsychology, VU University Amsterdam, Amsterdam, The Netherlands
*
*Address for correspondence: N. N. J. Rommelse, M.S., VU University Amsterdam, Department of Clinical Neuropsychology, Van der Boechorststraat 1, 1081 BT Amsterdam, The Netherlands. (Email: nnj.rommelse@psy.vu.nl)
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Abstract

Background

Impairments in executive functioning (EF) and intelligence quotient (IQ) are frequently observed in children with attention deficit hyperactivity disorder (ADHD). The aim of this paper was twofold: first, to examine whether both domains are viable endophenotypic candidates for ADHD and second to investigate whether deficits in both domains tend to co-segregate within families.

Method

A large family-based design was used, including 238 ADHD families (545 children) and 147 control families (271 children). Inhibition, visuospatial and verbal working memory, and performance and verbal IQ were analysed.

Results

Children with ADHD, and their affected and non-affected siblings were all impaired on the EF measures and verbal IQ (though unimpaired on performance IQ) and all measures correlated between siblings. Correlations and sibling cross-correlations were not significant between EF and IQ, though they were significant between the measures of one domain. Group differences on EF were not explained by group differences on IQ and vice versa. The discrepancy score between EF and IQ correlated between siblings, indicating that siblings resembled each other in their EF–IQ discrepancy instead of having generalized impairments across both domains. Siblings of probands who had an EF but not IQ impairment, showed a comparable disproportionate lower EF score in relation to IQ score. The opposite pattern was not significant.

Conclusions

The results supported the viability of EF and IQ as endophenotypic candidates for ADHD. Most findings support an independent familial segregation of both domains. Within EF, similar familial factors influenced inhibition and working memory. Within IQ, similar familial factors influenced verbal and performance IQ.

Keywords

Attention deficit hyperactivity disorderendophenotypeexecutive functionsintelligencesibling
Type
Original Articles
Information
Psychological Medicine , Volume 38 , Issue 11 , November 2008 , pp. 1595 - 1606
Copyright
Copyright © 2008 Cambridge University Press

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References

APA (1994). Diagnostic and Statistical Manual for Mental Disorders (DSM-IV), 4th edn. American Psychiatric Press: Washington, DC.Google Scholar
Ardila, A, Pineda, D, Rosselli, M (2000). Correlation between intelligence test scores and executive function measures. Archives of Clinical Neuropsychology 15, 31–36.Google Scholar
Asarnow, RF, Nuechterlein, KH, Subotnik, KL, Fogelson, DL, Torquato, RD, Payne, DL, Asamen, J, Mintz, J, Guthrie, D (2002). Neurocognitive impairments in nonpsychotic parents of children with schizophrenia and attention-deficit/hyperactivity disorder. Archives of General Psychiatry 59, 1053–1060.CrossRefGoogle ScholarPubMed
Barnett, R, Maruff, P, Vance, A, Luk, ESL, Costin, J, Wood, C, Pantelis, C (2001). Abnormal executive functioning in attention deficit hyperactivity disorder: the effect of stimulant medication and age on spatial working memory. Psychological Medicine 31, 1107–1115.CrossRefGoogle ScholarPubMed
Benson, DF (1991). The role of frontal dysfunction in attention deficit hyperactivity disorder. Journal of Child Neurology 6, 9–12.Google Scholar
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
Boonstra, AM, Kooij, JJS, Buitelaar, JK, Oosterlaan, J, Sergeant, JA, Heister, JGAMA, Franke, B (2007). An exploratory study of the relationship between four candidate genes and neurocognitive performance in adult ADHD. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics. Published online: 20 September 2007. doi:10.1002/ajmg.b.30595.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.CrossRefGoogle ScholarPubMed
Brookes, K, Xu, X, Chen, W, Zhou, K, Neale, B, Lowe, N, Aneey, R, Franke, B, Gill, M, Ebstein, R, Buitelaar, J, Sham, P, Campbell, D, Knight, J, Andreou, P, Altink, M, Arnold, R, Boer, F, Buschgens, C, Butler, L, Christiansen, H, Feldman, L, Fleischman, K, Fliers, E, Howe-Forbes, R, Goldfarb, A, Heise, A, Gabriels, I, Korn-Lubetzki, I, Marco, R, Medad, S, Minderaa, R, Mulas, F, Muller, U, Mulligan, A, Rabin, K, Rommelse, N, Sethna, V, Sorohan, J, Uebel, H, Psychogiou, L, Weeks, A, Barrett, R, Craig, I, Banaschewski, T, Sonuga-Barke, E, Eisenberg, J, Kuntsi, J, Manor, I, McGuffin, P, Miranda, A, Oades, R, Plomin, R, Roeyers, H, Rothenberger, A, Sergeant, J, Steinhausen, H, Taylor, E, Thompson, M, Faraone, S, Asherson, P, Johansson, L (2006). The analysis of 51 genes in DSM-IV combined type attention deficit hyperactivity disorder: association signals in DRD4, DAT1 and 16 other genes. Molecular Psychiatry 11, 934–953.CrossRefGoogle ScholarPubMed
Bull, R, Scerif, G (2001). Executive functioning as a predictor of children's mathematics ability: inhibition, switching, and working memory. Developmental Neuropsychology 19, 273–293.Google Scholar
Castellanos, FX, Tannock, R (2002). Neuroscience of attention-deficit/hyperactivity disorder: the search for endophenotypes. Nature Reviews Neuroscience 3, 617–628.CrossRefGoogle ScholarPubMed
Clark, C, Prior, M, Kinsella, GJ (2000). Do executive function deficits differentiate between adolescents with ADHD and oppositional defiant/conduct disorder? A neuropsychological study using the Six Elements Test and Hayling Sentence Completion Test. Journal of Abnormal Child Psychology 28, 403–414.Google Scholar
Cohen, J (1988). Statistical Power Analysis for the Behavioral Sciences, 2nd edn. Erlbaum: Hillsdale, NJ.Google Scholar
Conners, K (1996). Rating Scales in ADHD. Duke University Medical Center: Durham, NC.Google ScholarPubMed
Conway, AR, Kane, MJ, Engle, RW (2003). Working memory capacity and its relation to general intelligence. Trends in Cognitive Sciences 7, 547–552.CrossRefGoogle ScholarPubMed
Crosbie, J, Schachar, R (2001). Deficient inhibition as a marker for familial ADHD. American Journal of Psychiatry 158, 1884–1890.Google Scholar
De Sonneville, LMJ (1999). Amsterdam Neuropsychological Task: a computer-aided assessment program. In Cognitive Ergonomics, Clinical Assessment and Computer-Assisted Learning: Computers in Psychology, vol. 6 (ed. Den Brinker, B. P. L. M., Beek, P. J., Brand, A. N., Maarse, S. J. and Mulder, L. J. M.), pp. 204–217. Swets & Zeitlinger: Lisse, The Netherlands.Google Scholar
`, AE (2006). Executive functions in attention-deficit/hyperactivity disorder. Journal of Clinical Psychiatry 67 (Suppl. 8), 21–26.Google ScholarPubMed
Doyle, AE, Biederman, J, Seidman, LJ, Reske-Nielsen, JJ, Faraone, SV (2005 a). Neuropsychological functioning in relatives of girls with and without ADHD. Psychological Medicine 35, 1121–1132.Google Scholar
Doyle, AE, Faraone, SV, Seidman, LJ, Willcutt, EG, Nigg, JT, Waldman, ID, Pennington, BF, Peart, J, Biederman, J (2005 b). Are endophenotypes based on measures of executive functions useful for molecular genetic studies of ADHD? Journal of Child Psychology and Psychiatry 46, 774–803.CrossRefGoogle ScholarPubMed
Duncan, J (2005). Frontal lobe function and general intelligence: why it matters. Cortex 41, 215–217.Google Scholar
Duncan, J, Burgess, P, Emslie, H (1995). Fluid intelligence after frontal lobe lesions. Neuropsychologia 33, 261–268.Google Scholar
Duncan, J, Emslie, H, Williams, P, Johnson, R, Freer, C (1996). Intelligence and the frontal lobe: the organization of goal-directed behavior. Cognitive Psychology 30, 257–303.Google Scholar
Durston, S (2003). A review of the biological basis of ADHD. What have we learned from imaging studies? Mental Retardation and Developmental Disabilities Research Reviews 9, 184–195.Google Scholar
Engle, RW (2002). Working memory capacity as executive attention. Current Directions in Psychological Science 11, 19–23.Google Scholar
Faraone, SV, Biederman, J, Lehman, BK, Spencer, T, Norman, D, Seidman, LJ, Kraus, I, Perrin, J, Chen, WJ, Tsuang, MT (1993). Intellectual performance and school failure in children with attention deficit hyperactivity disorder and in their siblings. Journal of Abnormal Psychology 102, 616–623.CrossRefGoogle ScholarPubMed
Faraone, SV, Biederman, J, Mennin, D, Gershon, J, Tsuang, MT (1996). A prospective four-year follow-up study of children at risk for ADHD: psychiatric, neuropsychological, and psychosocial outcome. Journal of the American Academy of Child Adolescent Psychiatry 35, 1449–1459.CrossRefGoogle ScholarPubMed
Frazier, TW, Demaree, HA, Youngstrom, EA (2004). Meta-analysis of intellectual and neuropsychological test performance in attention-deficit/hyperactivity disorder. Neuropsychology 18, 543–555.Google Scholar
Fuster, JM (1997). The Prefrontal Cortex: Anatomy, Physiology and Neuropsychology of the Frontal Lobe. Raven Press: New York.Google Scholar
Goodman, R (1997). The strengths and difficulties questionnaire: a research note. Journal of Child Psychology and Psychiatry 1, 581–586.Google Scholar
Gottesman, II, Gould, TD (2003). The endophenotype concept in psychiatry: etymology and strategic intentions. American Journal of Psychiatry 160, 636–645.Google Scholar
Gray, JR, Chabris, CF, Braver, TS (2003). Neural mechanisms of general fluid intelligence. Nature Neuroscience 6, 316–322.Google Scholar
Groth-Marnat, G (1997). Handbook of Psychological Assessment, 3rd edn. Wiley: New York.Google Scholar
Haier, RJ, Jung, RE, Yeo, RA, Head, K, Alkire, MT (2004). Structural brain variation and general intelligence. NeuroImage 23, 425–433.Google Scholar
Heilman, KM, Voeller, KKS, Nadeau, SE (1991). A possible pathophysiological substrate of attention deficit hyperactivity disorder. Journal of Child Neurology 6, 76–81.Google Scholar
Khan, SA, Faraone, SV (2006). The genetics of ADHD: a literature review of 2005. Current Psychiatry Reports 8, 393–397.Google 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 Neuropsychiatric Genetics 124B, 41–47.CrossRefGoogle ScholarPubMed
Lezak, MD (1995). Neuropsychological Assessment. Oxford University Press: New York.Google Scholar
Logan, GD (1994). On the ability to inhibit thought and action: a users' guide to the stop signal paradigm. In Inhibitory Processes in Attention, Memory, and Language (ed. Dagenbach and, D.Carr, T. H.), pp. 189–239. Academic Press: San Diego.Google Scholar
Logan, GD, Cowan, WB (1984). On the ability to inhibit thought and action: a theory of an act of control. Psychological Review 91, 295–327.Google Scholar
Mahone, EM, Hagelthorn, KM, Cutting, LE, Schuerholz, LJ, Pelletier, SF, Rawlins, C, Singer, HS, Denckla, MB (2002). Effects of IQ on executive function measures in children with ADHD. Child Neuropsychology 8, 52–65.Google Scholar
Mariani, MA, Barkley, RA (1997). Neuropsychological and academic functioning in preschool boys with attention deficit hyperactivity disorder. Developmental Neuropsychology 13, 111–129.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
Mattes, JA (1980). The role of frontal lobe dysfunction in childhood hyperkinesis. Comprehensive Psychiatry 21, 358–369.CrossRefGoogle ScholarPubMed
Mill, J, Caspi, A, Williams, BS, Craig, I, Taylor, A, Polo-Tomas, M, Berridge, CW, Poulton, R, Moffitt, TE (2006). Prediction of heterogeneity in intelligence and adult prognosis by genetic polymorphisms in the dopamine system among children with attention-deficit/hyperactivity disorder. Archives of General Psychiatry 63, 462–469.CrossRefGoogle ScholarPubMed
Miyake, A, Friedman, NP, Emerson, MJ, Witzki, AH, Howerter, A (2000). The unity and diversity of executive functions and their contributions to complex ‘frontal lobe’ tasks: a latent variable analysis. Cognitive Psychology 41, 49–100.CrossRefGoogle ScholarPubMed
Miyake, A, Friedman, NP, Rettinger, DA, Shah, P, Hegarty, M (2001). How are visuospatial working memory, executive functioning, and spatial abilities related? A latent-variable analysis. Journal of Experimental Psychology 130, 621–640.CrossRefGoogle ScholarPubMed
Murphy, KR, Barkley, RA (1996). Parents of children with attention-deficit/hyperactivity disorder: psychological and attentional impairment. American Journal of Orthopsychiatry 66, 93–102.Google Scholar
Nigg, JT (1999). The ADHD response-inhibition deficit as measured by the stop task: replication with DSM–IV combined type, extension, and qualification. Journal of Abnormal Child Psychology 27, 393–402.Google Scholar
Nigg, JT, Blaskey, LG, Huang-Pollock, CL, Rappley, MD (2002). Neuropsychological executive functions and DSM-IV ADHD subtypes. Journal of the American Academy of Child and Adolescent Psychiatry 41, 59–66.CrossRefGoogle ScholarPubMed
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
Oosterlaan, J, Logan, GD, Sergeant, JA (1998). Response inhibition in AD/HD, CD, comorbid AD/HD+CD, anxious, and control children: a meta-analysis of studies with the stop task. Journal of Child Psychology and Psychiatry 39, 411–425.Google ScholarPubMed
Oosterlaan, J, Scheres, A, Sergeant, JA (2005). Which executive functioning deficits are associated with AD/HD, ODD/CD and comorbid AD/HD+ODD/CD? Journal of Abnormal Child Psychology 33, 69–85.Google Scholar
Oosterlaan, J, Sergeant, JA (1996). Inhibition in ADHD, anxious and aggressive children: a biologically based model of child psychology. Journal of Abnormal Child Psychology 24, 19–36.Google Scholar
Pelham, WE, Aronoff, HR, Midlam, JK, Shapiro, CJ, Gnagy, EM, Chronis, AM, Onyango, AN, Forehand, G, Nguyen, A, Waxmonsky, J (1999). A comparison of ritalin and adderall: efficacy and time-course in children with attention-deficit/hyperactivity disorder. Pediatrics 103, e43.CrossRefGoogle ScholarPubMed
Pennington, BF, Ozonoff, S (1996). Executive functions and developmental psychopathology. Journal of Child Psychology and Psychiatry 37, 51–87.Google Scholar
Plomin, R, Spinath, FM (2005). Intelligence: genetics, genes, and genomics. Journal of Personality and Social Psychology 86, 112–129.CrossRefGoogle Scholar
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
Rommelse, NNJ, Oosterlaan, J, Buitelaar, J, Faraone, SV, Sergeant, JA (2007). Time reproduction in children with ADHD and their non-affected siblings. Journal of the American Academy of Child and Adolescent Psychiatry 46, 582–590.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.Google Scholar
Scheres, A, Oosterlaan, J, Sergeant, JA (2006). Speed of inhibition predicts teacher-rated medication response in boys with attention deficit hyperactivity disorder. Journal of Disability, Development and Education 1, 93–109.CrossRefGoogle Scholar
Schretlen, D, Pearlson, GD, Anthony, JC, Aylward, EH, Augustine, AM, Davis, A, Barta, P (2000). Elucidating the contributions of processing speed, executive ability, and frontal lobe volume to normal age-related differences in fluid intelligence. Journal of the International Neuropsychological Society 6, 52–61.CrossRefGoogle ScholarPubMed
Seidman, L, Biederman, J, Monuteaux, M, Weber, W, Faraone, SV (2000). Neuropsychological functioning in nonreferred siblings of children with attention deficit hyperactivity disorder. Journal of Abnormal Psychology 109, 252–265.Google Scholar
Seidman, L, Doyle, A, Fried, R, Valera, E, Crum, K, Matthews, L (2004). Neuropsychological functioning in adults with attention-deficit/hyperactivity disorder. Psychiatric Clinics of North America 27, 261–282.Google Scholar
Seidman, LJ, Biederman, J, Faraone, SV, Milberger, S, Norman, D, Seiverd, K, Benedict, K, Guite, J, Mick, E, Kiley, K (1995). Effects of family history and co-morbidity on the neuropsychological performance of children with ADHD: preliminary findings. Journal of the American Academy of Child and Adolescent Psychiatry 34, 1015–1024.CrossRefGoogle ScholarPubMed
Sergeant, JA, Geurts, H, Oosterlaan, J (2002). How specific is a deficit of executive functioning for attention-deficit/hyperactivity disorder? Behavioural Brain Research 130, 3–28.CrossRefGoogle ScholarPubMed
Slaats-Willemse, D, Swaab-Barneveld, H, De Sonneville, L, Buitelaar, J (2005). Familial clustering of executive functioning in affected sibling pair families with ADHD. Journal of the American Academy of Child and Adolescent Psychiatry 44, 385–391.Google Scholar
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
Smith, EE, Jonides, J (1999). Storage and executive processes in the frontal lobe. Science 283, 1657–1661.Google Scholar
Stuss, DT, Benson, DF (1986). The Frontal Lobes. Raven Press: New York.Google Scholar
Tabachnick, BG, Fidell, LS (2001). Using Multivariate Statistics, 4th edn. Allyn and Bacon: Needham Heights, MA.Google Scholar
Taylor, EA (1986). Childhood hyperactivity. British Journal of Psychiatry 149, 562–573.Google Scholar
Toga, AW, Thompson, PM (2005). Genetics of brain structure and intelligence. Annual Review of Neuroscience 28, 1–23.CrossRefGoogle ScholarPubMed
Waldman, ID (2005). Statistical approaches to complex phenotypes: evaluating neuropsychological endophenotypes for attention-deficit/hyperactivity disorder. Biological Psychiatry 57, 1347–1356.CrossRefGoogle ScholarPubMed
Waldman, ID, Nigg, JT, Gizer, IR, Park, L, Rappley, MD, Friderici, K (2006). The adrenergic receptor α-2A gene (ADRA2A) and neuropsychological executive functions as putative endophenotypes for childhood ADHD. Cognitive, Affective, and Behavioral Neuroscience 6, 18–30.Google Scholar
Wechsler, D (1944). The Measurement of Adult Intelligence. Williams and Wilkins: Baltimore.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, Groisser, DB (1991). A normative-developmental study of executive function: a window on prefrontal function in children. Developmental Neuropsychology 7, 131–149.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