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

  • N. N. J. Rommelse (a1), M. E. Altink (a2), J. Oosterlaan (a1), C. J. M. Buschgens (a2), J. Buitelaar (a2) and J. A. Sergeant (a1)...
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.

Copyright
Corresponding author
*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)
References
Hide All
APA (1994). Diagnostic and Statistical Manual for Mental Disorders (DSM-IV), 4th edn. American Psychiatric Press: Washington, DC.
Ardila A, Pineda D, Rosselli M (2000). Correlation between intelligence test scores and executive function measures. Archives of Clinical Neuropsychology 15, 3136.
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, 10531060.
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, 11071115.
Benson DF (1991). The role of frontal dysfunction in attention deficit hyperactivity disorder. Journal of Child Neurology 6, 912.
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.
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.
Boonstra AM, Oosterlaan J, Sergeant JA, Buitelaar JK (2005). Executive functioning in adult ADHD: a meta-analytic review. Psychological Medicine 35, 10971108.
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, 934953.
Bull R, Scerif G (2001). Executive functioning as a predictor of children's mathematics ability: inhibition, switching, and working memory. Developmental Neuropsychology 19, 273293.
Castellanos FX, Tannock R (2002). Neuroscience of attention-deficit/hyperactivity disorder: the search for endophenotypes. Nature Reviews Neuroscience 3, 617628.
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, 403414.
Cohen J (1988). Statistical Power Analysis for the Behavioral Sciences, 2nd edn. Erlbaum: Hillsdale, NJ.
Conners K (1996). Rating Scales in ADHD. Duke University Medical Center: Durham, NC.
Conway AR, Kane MJ, Engle RW (2003). Working memory capacity and its relation to general intelligence. Trends in Cognitive Sciences 7, 547552.
Crosbie J, Schachar R (2001). Deficient inhibition as a marker for familial ADHD. American Journal of Psychiatry 158, 18841890.
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. 204217. Swets & Zeitlinger: Lisse, The Netherlands.
` AE (2006). Executive functions in attention-deficit/hyperactivity disorder. Journal of Clinical Psychiatry 67 (Suppl. 8), 2126.
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, 11211132.
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, 774803.
Duncan J (2005). Frontal lobe function and general intelligence: why it matters. Cortex 41, 215217.
Duncan J, Burgess P, Emslie H (1995). Fluid intelligence after frontal lobe lesions. Neuropsychologia 33, 261268.
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, 257303.
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, 184195.
Engle RW (2002). Working memory capacity as executive attention. Current Directions in Psychological Science 11, 1923.
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, 616623.
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, 14491459.
Frazier TW, Demaree HA, Youngstrom EA (2004). Meta-analysis of intellectual and neuropsychological test performance in attention-deficit/hyperactivity disorder. Neuropsychology 18, 543555.
Fuster JM (1997). The Prefrontal Cortex: Anatomy, Physiology and Neuropsychology of the Frontal Lobe. Raven Press: New York.
Goodman R (1997). The strengths and difficulties questionnaire: a research note. Journal of Child Psychology and Psychiatry 1, 581586.
Gottesman II, Gould TD (2003). The endophenotype concept in psychiatry: etymology and strategic intentions. American Journal of Psychiatry 160, 636645.
Gray JR, Chabris CF, Braver TS (2003). Neural mechanisms of general fluid intelligence. Nature Neuroscience 6, 316322.
Groth-Marnat G (1997). Handbook of Psychological Assessment, 3rd edn. Wiley: New York.
Haier RJ, Jung RE, Yeo RA, Head K, Alkire MT (2004). Structural brain variation and general intelligence. NeuroImage 23, 425433.
Heilman KM, Voeller KKS, Nadeau SE (1991). A possible pathophysiological substrate of attention deficit hyperactivity disorder. Journal of Child Neurology 6, 7681.
Khan SA, Faraone SV (2006). The genetics of ADHD: a literature review of 2005. Current Psychiatry Reports 8, 393397.
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, 4147.
Lezak MD (1995). Neuropsychological Assessment. Oxford University Press: New York.
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. 189239. Academic Press: San Diego.
Logan GD, Cowan WB (1984). On the ability to inhibit thought and action: a theory of an act of control. Psychological Review 91, 295327.
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, 5265.
Mariani MA, Barkley RA (1997). Neuropsychological and academic functioning in preschool boys with attention deficit hyperactivity disorder. Developmental Neuropsychology 13, 111129.
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, 377384.
Mattes JA (1980). The role of frontal lobe dysfunction in childhood hyperkinesis. Comprehensive Psychiatry 21, 358369.
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, 462469.
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, 49100.
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, 621640.
Murphy KR, Barkley RA (1996). Parents of children with attention-deficit/hyperactivity disorder: psychological and attentional impairment. American Journal of Orthopsychiatry 66, 93102.
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, 393402.
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, 5966.
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.
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, 411425.
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, 6985.
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, 1936.
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.
Pennington BF, Ozonoff S (1996). Executive functions and developmental psychopathology. Journal of Child Psychology and Psychiatry 37, 5187.
Plomin R, Spinath FM (2005). Intelligence: genetics, genes, and genomics. Journal of Personality and Social Psychology 86, 112129.
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.
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, 582590.
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.
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, 93109.
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, 5261.
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, 252265.
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, 261282.
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, 10151024.
Sergeant JA, Geurts H, Oosterlaan J (2002). How specific is a deficit of executive functioning for attention-deficit/hyperactivity disorder? Behavioural Brain Research 130, 328.
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, 385391.
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.
Smith EE, Jonides J (1999). Storage and executive processes in the frontal lobe. Science 283, 16571661.
Stuss DT, Benson DF (1986). The Frontal Lobes. Raven Press: New York.
Tabachnick BG, Fidell LS (2001). Using Multivariate Statistics, 4th edn. Allyn and Bacon: Needham Heights, MA.
Taylor EA (1986). Childhood hyperactivity. British Journal of Psychiatry 149, 562573.
Toga AW, Thompson PM (2005). Genetics of brain structure and intelligence. Annual Review of Neuroscience 28, 123.
Waldman ID (2005). Statistical approaches to complex phenotypes: evaluating neuropsychological endophenotypes for attention-deficit/hyperactivity disorder. Biological Psychiatry 57, 13471356.
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, 1830.
Wechsler D (1944). The Measurement of Adult Intelligence. Williams and Wilkins: Baltimore.
Wechsler D (2000). WAIS-III Nederlandstalige Bewerking. Technische Handleiding. The Psychological Corporation: London.
Wechsler D (2002). WISC-III Handleiding. The Psychological Corporation: London.
Welsh MC, Pennington BF, Groisser DB (1991). A normative-developmental study of executive function: a window on prefrontal function in children. Developmental Neuropsychology 7, 131149.
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.
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