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Attention-Deficit/Hyperactivity Disorder Endophenotypes

      Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable disorder with a multifactorial pattern of inheritance. For complex conditions such as this, biologically based phenotypes that lie in the pathway from genes to behavior may provide a more powerful target for molecular genetic studies than the disorder as a whole. Although their use in ADHD is relatively new, such “endophenotypes” have aided the clarification of the etiology and pathophysiology of several other conditions in medicine and psychiatry. In this article, we review existing data on potential endophenotypes for ADHD, emphasizing neuropsychological deficits because assessment tools are cost effective and relatively easy to implement. Neuropsychological impairments, as well as measures from neuroimaging and electrophysiological paradigms, show correlations with ADHD and evidence of heritability, but the familial or genetic overlap between these constructs and ADHD remains unclear. We conclude that these endophenotypes will not be a quick fix for the field but offer potential if careful consideration is given to issues of heterogeneity, measurement and statistical power.

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      References

        • Adams J.
        • Crosbie J.
        • Wigg K.
        • Ickowicz A.
        • Pathare T.
        • Roberts W.
        • et al.
        Glutamate receptor, ionotropic, N-methyl D-aspartate 2A (GRIN2A) gene as a positional candidate for attention-deficit/hyperactivity disorder in the 16p13 region.
        Mol Psychiatry. 2004; 9: 494-499
        • Alberts-Corush J.
        • Firestone P.
        • Goodman J.T.
        Attention and impulsivity characteristics of the biological and adoptive parents of hyperactive and normal control children.
        Am J Orthopsychiatry. 1986; 56: 413-423
        • Almasy L.
        • Blangero J.
        Endophenotypes as quantitative risk factors for psychiatric disease.
        Am J Med Genet. 2001; 105: 42-44
        • Ando J.
        • Ono Y.
        • Wright M.J.
        Genetic structure of spatial and working memory.
        Behav Genet. 2001; 31: 615-624
        • Arcos-Burgos M.
        • Castellanos F.X.
        • Konecki D.
        • Lopera F.
        • Pineda D.
        • Palacio J.D.
        • et al.
        Pedigree disequilibrium test (PDT) replicates association and linkage between DRD4 and ADHD in multigenerational and extended pedigrees from a genetic isolate.
        Mol Psychiatry. 2004; 9: 252-259
        • Asarnow R.F.
        • Nuechterlein K.H.
        • Subotnik K.L.
        • Fogelson D.L.
        • Torquato R.D.
        • Payne D.L.
        • et al.
        Neurocognitive impairments in nonpsychotic parents of children with schizophrenia and attention-deficit/hyperactivity disorder.
        Arch Gen Psychiatry. 2002; 59: 1053-1060
        • Auerbach J.G.
        • Benjamin J.
        • Faroy M.
        • Geller V.
        • Ebstein R.
        DRD4 related to infant attention and information processing.
        Psychiatr Genet. 2001; 11: 31-35
        • Bakker S.
        • van der Meulen E.
        • Buitelaar J.
        • Sandkuijl L.
        • Pauls D.
        • Monsuur A.
        • et al.
        A whole-genome scan in 164 Dutch sib pairs with attention-deficit/hyperactivity disorder.
        Am J Hum Genet. 2003; 72: 1251-1260
        • Barkley R.A.
        ADHD and the nature of self-control. Guilford Press, New York1997
        • Barry R.J.
        • Clarke A.R.
        • Johnstone S.J.
        A review of electrophysiology in attention-deficit/hyperactivity disorder: I. Qualitative and quantitative electroencephalography.
        Clin Neurophysiol. 2003; 114: 171-183
        • Barry R.J.
        • Johnstone S.J.
        • Clarke A.R.
        A review of electrophysiology in attention-deficit/hyperactivity disorder: II. Event-related potentials.
        Clin Neurophysiol. 2003; 114: 184-198
        • Bartfai A.
        • Pedersen N.L.
        • Asarnow R.F.
        • Schalling D.
        Genetic factors for the span of apprehension test.
        Psychiatry Research. 1991; 38: 115-124
        • Berquin P.C.
        • Giedd J.N.
        • Jacobsen L.K.
        • Hamburger S.D.
        • Krain A.L.
        • Rapoport J.L.
        • et al.
        Cerebellum in attention-deficit hyperactivity disorder.
        Neurology. 1998; 50: 1087-1093
        • Borecki I.B.
        • Rao D.C.
        • Yaouanq J.
        • Lalouel J.M.
        Serum ferritin as a marker of affection for genetic hemochromatosis.
        Hum Hered. 1990; 40: 159-166
        • Campana A.
        • Macciardi F.
        • Gambini O.
        • Scarone S.
        The Wisconsin Card Sorting Test (WCST) performance in normal subjects.
        Neuropsychobiology. 1996; 34: 14-17
        • Carlson S.R.
        • Iacono W.G.
        • McGue M.
        P300 amplitude in adolescent twins discordant and concordant for alcohol use disorders.
        Biol Psychol. 2002; 61: 203-227
        • Carmelli D.
        • Swan G.E.
        • DeCarli C.
        • Reed T.
        Quantitative genetic modeling of regional brain volumes and cognitive performance in older male twins.
        Biol Psychol. 2002; 61: 139-155
        • Castellanos F.X.
        • Lee P.P.
        • Sharp W.
        • Jeffries N.O.
        • Greenstein D.K.
        • Clasen L.S.
        • et al.
        Developmental trajectories of brain volume abnormalities in children and adolescents with attention-deficit/hyperactivity disorder.
        JAMA. 2002; 288: 1740-1748
        • Castellanos F.X.
        • Tannock R.
        Neuroscience of attention-deficit/hyperactivity disorder.
        Nat Rev Neurosci. 2002; 3: 617-628
        • Chabot R.J.
        • Serfontein G.
        Quantitative electroencephalographic profiles of children with attention deficit disorder.
        Biol Psychiatry. 1996; 40: 951-963
        • Clarke A.
        • Barry R.
        • McCarthy R.
        • Selikowitz M.
        • Brown C.
        EEG evidence for a new conceptualisation of attention deficit hyperactivity disorder.
        Clin Neurophysiol. 2002; 113: 1036-1044
        • Denckla M.B.
        A theory and model of executive function.
        in: Lyon G.R. Krasgenor N.A. Attention, Memory and Executive Function. Paul H. Brooks, Baltimore, MD1996: 263-277
        • Dolan C.V.
        • Boomsma D.I.
        Optimal selection of sib pairs from random samples for linkage analysis of a QTL using the EDAC test.
        Behav Genet. 1998; 28: 197-206
      1. Doyle AE, Biederman J, Seidman L, Reske-Nielsen J, Faraone SV (in press-a): Neuropsychological functioning in relatives of girls with and without ADHD. Psychol Med.

        • Doyle A.E.
        • Biederman J.
        • Seidman L.
        • Weber W.
        • Faraone S.
        Diagnostic efficiency of neuropsychological test scores for discriminating boys with and without attention deficit hyperactivity disorder.
        J Consult Clin Psychol. 2000; 68: 477-488
        • Doyle A.E.
        • Faraone S.
        Familial links between ADHD, conduct disorder and bipolar disorder.
        Curr Psychiatry Rep. 2002; 4: 146-152
      2. Doyle AE, Faraone SV, Seidman LJ, Willcutt EG, Nigg JT, Waldman ID, et al (in press-b): Are endophenotypes based on measures of executive functions useful for molecular genetic studes of ADHD. J Child Psychol Psychiatry.

        • Durston S.
        • Hulshoff H.
        • Schnack H.G.
        • Buitelaar J.K.
        • Steenhuis M.P.
        • Minderaa R.B.
        • et al.
        Magnetic resonance imaging of boys with attention-deficit/hyperactivity disorder and their unaffected siblings.
        J Am Acad Child Adolesc Psychiatry. 2004; 43: 332-340
        • Eaves L.
        • Meyer J.
        Locating human quantitative trait loci.
        Behav Genet. 1994; 24: 443-455
        • Egan M.F.
        • Goldberg T.E.
        • Gscheidle T.
        • Weirich M.
        • Rawlings R.
        • Hyde T.M.
        • et al.
        Relative risk for cognitive impairments in siblings of patients with schizophrenia.
        Biol Psychiatry. 2001; 50: 98-107
        • Ernst M.
        • Liebenauer L.
        • King A.
        • Fitzgerald G.
        • Cohen R.
        • Zametkin A.
        Reduced brain metabolism in hyperactive girls.
        J Am Acad Child Adolesc Psychiatry. 1994; 33: 858-868
        • Fan J.
        • Wu Y.
        • Fosella J.A.
        • Posner M.I.
        Assessing the heritability of attentional networks.
        BMC Neurosci. 2001; 2: 14
        • Faraone S.
        • Kremen W.
        • Lyons M.
        • Pepple J.
        • Seidman L.
        • Tsuang M.
        Diagnostic accuracy and linkage analysis.
        Am J Psychiatry. 1995; 152: 1286-1290
        • Faraone S.V.
        Report from the third international meeting of the Attention-Deficit Hyperactivity Disorder Molecular Genetics Network.
        Am J Med Genet. 2002; 114: 272-276
        • Faraone S.V.
        • Biederman J.
        Neurobiology of attention-deficit hyperactivity disorder.
        Biol Psychiatry. 1998; 44: 951-958
        • Faraone S.V.
        • Biederman J.
        • Mennin D.
        • Russell R.L.
        Bipolar and antisocial disorders among relatives of ADHD children.
        Am J Med Genet. 1998; 81: 108-116
        • Faraone S.V.
        • Biederman J.
        • Monuteaux M.C.
        Toward guidelines for pedigree selection in genetic studies of attention deficit hyperactivity disorder.
        Genet Epidemiol. 2000; 18: 1-16
        • Faraone S.V.
        • Perlis R.H.
        • Doyle A.E.
        • Smoller J.W.
        • Goralnick J.
        • Holmgren M.A.
        • et al.
        Molecular genetics of attention-deficit/hyperactivity disorder.
        Biol Psychiatry. 2005; 57: 1313-1323
        • Faraone S.V.
        • Tsuang D.
        • Tsuang M.T.
        Genetics and Mental Disorders. Guilford Press, New York1999
        • Faraone S.V.
        • Tsuang M.T.
        Heterogeneity and the genetics of bipolar disorder.
        Am J Hum Genet. 2003; 123C: 1-9
        • Fisher S.E.
        • Francks C.
        • McCracken J.T.
        • McGough J.J.
        • Marlow A.J.
        • MacPhie I.L.
        • et al.
        A genomewide scan for loci involved in attention-deficit/hyperactivity disorder.
        Am J Hum Genet. 2002; 70: 1183-1196
        • Fossella J.A.
        • Sommer T.
        • Fan J.
        • Wu Y.
        • Swanson J.M.
        • Pfaff D.W.
        Assessing the molecular genetics of attention networks.
        BMC Neurosci. 2002; 4: 14
        • Freedman R.
        • Adler L.E.
        • Leonard S.
        Alternative phenotypes for the complex genetics of schizophrenia.
        Biol Psychiatry. 1999; 45: 551-558
        • Freedman R.
        • Leonard S.
        • Gault J.
        • Hopkins J.
        • Cloninger C.
        • Kaufmann C.
        • et al.
        Linkage disequilibrium for schizophrenia at the chromosome 15q13-14 locus of the alpha7-nicotinic acetylcholine receptor subunit gene (CHRNA7).
        Am J Med Genet (Neuropsychiatr Genet). 2001; 105: 20-22
        • Gainetdinov R.R.
        • Wetsel W.C.
        • Jones S.R.
        • Levin E.D.
        • Jaber M.
        • Caron M.G.
        Role of serotonin in the paradoxical calming effect of psychostimulants on hyperactivity.
        Science. 1999; 283: 397-402
        • Giedd J.
        • Blumenthal J.
        • Molloy E.
        • Castellanos F.
        Brain imaging of attention deficit/hyperactivity disorder.
        Ann N Y Acad Sci. 2001; 931: 33-49
        • Goldberg E.
        • Seidman L.J.
        Higher cortical functions in normals and in schizophrenia.
        in: Steinhauer S.R. Gruzelier J.H. Zubin J. Handbook of Schizophrenia. Volume 5: Neuropsychology, Psychophysiology and Information Processing. Elsevier Science, Amsterdam1991: 553-597
        • Goodman R.
        • Stevenson J.
        A twin study of hyperactivity: II. The aetiological role of genes, family relationships and perinatal adversity.
        J Child Psychol Psychiatry. 1989; 30: 691-709
        • Gottesman II,
        • Gould T.D.
        The endophenotype concept in psychiatry.
        Am J Psychiatry. 2003; 160: 636-645
        • Hauser E.R.
        • Watanabe R.M.
        • Duren W.L.
        • Bass M.P.
        • Langefeld C.D.
        • Boehnke M.
        Ordered subset analysis in genetic linkage mapping of complex traits.
        Genet Epidemiol. 2004; 27: 53-63
        • Hinshaw S.P.
        • Carte E.T.
        • Sarni N.
        • Treuting J.J.
        • Zupan B.
        Preadolescent girls with attention-deficit/hyperactivity disorder: II. Neuropsychological performance in relation to subtypes and individual classification.
        J Consult Clin Psychol. 2002; 70: 1099-1111
        • Holmes J.
        • Hever T.
        • Hewitt L.
        • Ball C.
        • Taylor E.
        • Rubia K.
        • Thaper A.
        A pilot twin study of psychological measures of attention deficit hyperactivity disorder.
        Behav Genet. 2002; 32: 389-395
        • Hudziak J.
        • Heath A.
        • Madden P.
        • Reich W.
        • Bucholz K.
        • Slutske W.
        • et al.
        Latent class and factor analysis of DSM-IV ADHD.
        J Am Acad Child Adolesc Psychiatry. 1998; 37: 848-857
        • Iacono W.G.
        • Carlson S.R.
        • Malone S.M.
        • McGue M.
        P3 event-related potential amplitude and the risk for disinhibitory disorders in adolescent boys.
        Arch Gen Psychiatry. 2002; 59: 750-757
        • Iacono W.G.
        • Malone S.M.
        • McGue M.
        Substance use disorders, externalizing psychopathology, and P300 event-related potential amplitude.
        Int J Psychophysiol. 2003; 48: 147-178
        • Johansen E.
        • Aase H.
        • Meyer A.
        • Sagvolden T.
        Attention-deficit/hyperactivity disorder (ADHD) behaviour explained by dysfunctioning reinforcement and extinction processes.
        Behav Brain Res. 2002; 130: 37-45
        • Joober R.
        • Gauthier J.
        • Lal S.
        • Bloom D.
        • Lalonde P.
        • Rouleau G.
        • et al.
        Catechol-O-methyltransferase Val-108/158-Met gene variants associated with performance on the Wisconsin Card Sorting Test.
        Arch Gen Psychiatry. 2002; 59: 662-663
        • Krabbendam L.
        • Marcelis M.
        • Delespaul P.
        • Jolles J.
        • van Os J.
        Single or multiple familial cognitive risk factors in schizophrenia?.
        Am J Med Genet (Neuropsychiatr Genet). 2001; 105: 183-188
        • Kuntsi J.
        • Stevenson J.
        Psychological mechanisms in hyperactivity: II. The Role of Genetic Factors.
        J Child Psychol Psychiatry. 2001; 42: 211-219
        • Kuntsi J.
        • Stevenson J.
        • Oosterlaan J.
        • Sonuga-Barke E.
        Test-retest reliability of new delay aversion task and executive function.
        Br J Dev Psychol. 2001; 19: 339-348
        • Lange C.
        • Lyon H.
        • DeMeo D.
        • Raby B.
        • Silverman E.K.
        • Weiss S.T.
        A new powerful non-parametric two-stage approach for testing multiple phenotypes in family-based association studies.
        Hum Hered. 2003; 56: 10-17
        • Langley K.
        • Marshall L.
        • van den Bree M.
        • Thomas H.
        • Owen M.
        • O’Donovan M.
        • et al.
        Association of the dopamine D4 receptor gene 7-repeat allele with neuropsychological test performance of children with ADHD.
        Am J Psychiatry. 2004; 161: 133-138
        • Leboyer M.
        • Bellivier F.
        • Nosten-Bertrand M.
        • Jouvent R.
        • Pauls D.
        • Mallet J.
        Psychiatric genetics.
        Trends Neurosci. 1998; 21: 102-105
        • Logan G.D.
        • Schachar R.J.
        • Tannock R.
        Impulsivity and inhibitory control.
        Psychol Sci. 1997; 8: 60-64
        • Lopez R.E.
        Hyperactivity in twins.
        Can Psychiatr Assoc J. 1965; 10: 421-426
        • Lyon G.R.
        • Krasnegor N.A.
        Attention, Memory, and Executive Function. Paul H. Brookes, Baltimore, MD1996
        • MacDonald III, A.W.
        • Carter C.S.
        Cognitive experimental approaches to investigating impaired cognition in schizophrenia.
        J Clin Neuropsychol. 2002; 24: 873-882
        • Malhotra A.K.
        • Kestler L.J.
        • Mazzanti C.
        • Bates J.A.
        • Goldberg T.
        • Goldman D.
        A functional polymorphism in the COMT gene and performance on a test of prefrontal cognition.
        Am J Psychiatry. 2002; 159: 652-654
        • Manor I.
        • Corbex M.
        • Eisenberg J.
        • Gritsenkso I.
        • Bachner-Melman R.
        • Tyano S.
        • et al.
        Association of the dopamine D5 receptor with attention deficit hyperactivity disorder (ADHD) and scores on a continuous performance test (TOVA).
        Am J Med Genet. 2004; 127B: 73-77
        • Manor I.
        • Tyano S.
        • Eisenberg J.
        • Bachner-Melman R.
        • Kotler M.
        • Ebstein R.P.
        The short DRD4 repeats confer risk to attention deficit hyperactivity disorder in a family-based design and impair performance on a continuous performance test (TOVA).
        Mol Psychiatry. 2002; 7: 790-794
        • Mattes J.A.
        The role of frontal lobe dysfunction in childhood hyperkinesis.
        Compr Psychiatry. 1980; 21: 358-369
        • McCracken J.T.
        • Smalley S.L.
        • McGough J.J.
        • Crawford L.
        • Del’Homme M.
        • Cantor R.M.
        • et al.
        Evidence for linkage of a tandem duplication polymorphism upstream of the dopamine D4 receptor gene (DRD4) with attention deficit hyperactivity disorder (ADHD).
        Mol Psychiatry. 2000; 5: 531-536
        • Mills S.
        • Langley K.
        • Van Den Bree M.
        • Street E.
        • Turic D.
        • Owen M.J.
        • et al.
        No evidence of association between catechol-O-methyltransferase (COMT) Val158Met genotype and performance on neuropsychological tasks in children with ADHD.
        BMC Psychiatry. 2004; 4: 15
        • Mostofsky S.
        • Reiss A.L.
        • Lockhart P.
        • Denckla M.B.
        Evaluation of cerebellar size in attention-deficit hyperactivity disorder.
        J Child Neurol. 1998; 13: 434-439
        • Mostofsky S.
        • Cooper K.
        • Kates W.
        • Denckla M.
        • Kaufmann W.
        Smaller prefrontal and premotor volumes in boys with attention-deficit/hyperactivity disorder.
        Biol Psychiatry. 2002; 52: 785-794
        • Murphy K.R.
        • Barkley R.A.
        Parents of children with attention-deficit/hyperactivity disorder.
        Am J Orthopsychiatry. 1996; 66: 93-102
        • Murphy K.R.
        • Barkley R.A.
        Parents of children with attention-deficit/hyperactivity disorder.
        Am J Orthopsychiatry. 1996; 66: 93-102
        • Myles-Worsley M.
        • Coon H.
        Genetic and developmental factors in spontaneous selective attention.
        Psychiatr Res. 1997; 71: 163-174
        • Nigg J.T.
        Is ADHD a disinhibitory disorder?.
        Psychol Bull. 2001; 127: 571-598
        • Nigg J.T.
        • Blaskey L.
        • Stawikcki J.
        • Sachek J.
        Evaluating endophenotype model of ADHD neuropsychological deficit.
        J Abnorm Psychol. 2004; 113: 614-625
        • Nigg J.T.
        • Swanson J.M.
        • Hinshaw S.P.
        Covert visual spatial attention in boys with attention deficit hyperactivity disorder.
        Neuropsychologia. 1997; 35: 165-176
        • Nigg J.T.
        • Willcutt E.G.
        • Doyle A.E.
        • Sonuga-Barke E.
        Causal heterogeneity in attention-deficit/hyperactivity disorder.
        Biol Psychiatry. 2005; 57: 1224-1230
        • Ogdie M.
        • Macphie I.
        • Minassian S.
        • Yang M.
        • Fisher S.
        • Francks C.
        • et al.
        A genomewide scan for attention-deficit/hyperactivity disorder in an extended sample.
        Am J Hum Genet. 2002; 72: 1268-1279
        • Pennington B.F.
        • Bennetto L.
        • McAleer O.K.
        • Roberts Jr, R.J.
        Executive functions and working memory.
        in: Lyon G.R. Krasnegor N.A. Attention, Memory and Executive Function. Paul H. Brookes Publishing Co, Baltimore, MD1996: 327-348
        • Pennington B.F.
        • Filipek P.A.
        • Lefly D.
        • Chhabildas N.
        • Kennedy D.N.
        • Simon J.H.
        • et al.
        A twin MRI study of size variations in human brain.
        J Cogn Neurosci. 2000; 12: 223-232
        • Pennington B.F.
        • Ozonoff S.
        Executive functions and developmental psychopathology.
        J Child Psychol Psychiatry. 1996; 37: 51-87
        • Plomin R.
        Genetics and general cognitive ability.
        Nature. 1999; 402: C25-C29
        • Polich J.
        • Pollock V.E.
        • Bloom F.E.
        Meta-analysis of P300 amplitude from males at risk for alcoholism.
        Psychol Bull. 1994; 115: 55-73
        • Posthuma D.
        • de Geus E.J.
        • Neale M.C.
        • Hulshoff Pol H.E.
        • Baare W.E.C.
        • Kahn R.S.
        • et al.
        Multivariate genetic analysis of brain structure in an extended twin design.
        Behav Genet. 2000; 30: 311-319
        • Rasmussen E.
        • Neuman R.
        • Heath A.
        • Levy F.
        • Hay D.
        • Todd R.
        Replication of the latent class structure of attention-deficit/hyperactivity disorder (ADHD) subtypes in a sample of Australian twins.
        J Child Psychol Psychiatry. 2002; 43: 1018-1028
        • Rhee S.H.
        • Waldman I.D.
        • Hay D.A.
        • Levy F.
        Sex differences in genetic and environmental influences on DSM-III-R attention-deficit/hyperactivity disorder.
        J Abnorm Psychol. 1999; 108: 24-41
        • Rice J.
        • Todorov A.
        Stability of diagnosis.
        Schizophr Bull. 1994; 20: 185-190
        • Risch N.
        Linkage strategies for genetically complex traits. I. Multilocus models.
        Am J Hum Genet. 1990; 46: 222-228
        • Risch N.
        Linkage strategies for genetically complex traits. II. The power of affected relative pairs.
        Am J Hum Genet. 1990; 46: 229-241
        • Risch N.
        • Zhang H.
        Extreme discordant sib pairs for mapping quantitative trait loci in humans.
        Science. 1995; 268: 1584-1589
        • Rowe D.C.
        • Stever C.
        • Giedinghagen L.N.
        • Gard J.M.
        • Cleveland H.H.
        • Terris S.T.
        • et al.
        Dopamine DRD4 receptor polymorphism and attention deficit hyperactivity disorder.
        Mol Psychiatry. 1998; 3: 419-426
        • Rubinstein M.
        • Phillips T.J.
        • Bunzow J.R.
        • Falzone T.L.
        • Dziewczapolski G.
        • Zhang G.
        • et al.
        Mice lacking dopamine D4 receptors are supersensitive to ethanol, cocaine, and methamphetamine.
        Cell. 1997; 90: 991-1001
        • Sagvolden T.
        • Aase H.
        • Zeiner P.
        • Berger D.
        Altered reinforcement mechanisms in attention-deficit/hyperactivity disorder.
        Behav Brain Res. 1998; 94: 61-71
        • Schachar R.
        • Tannock R.
        • Marriott M.
        • Logan G.
        Deficient inhibitory control in attention deficit hyperactivity disorder.
        J Abnorm Child Psychol. 1995; 23: 411-437
        • Seidman L.
        • Biederman J.
        • Monuteaux M.
        • Weber W.
        • Faraone S.V.
        Neuropsychological functioning in nonreferred siblings of children with attention deficit hyperactivity disorder.
        J Abnorm Psychol. 2000; 109: 252-265
        • Seidman L.J.
        • Doyle A.
        • Fried R.
        • Valera E.
        • Crum K.
        • Matthews L.
        Neuropsychological function in adults with attention-deficit/hyperactivity disorder.
        Psychiatr Clin North Am. 2004; 27: 261-282
        • Seidman L.
        • Valera E.
        The ADHD brain.
        in: Biederman J. ADHD Current Understanding of Etiology, Diagnosis, and Neurobiology. Veritas Institute for Medical Education, Boston2002: 44
        • Seidman L.
        • Valera E.
        • Makris N.
        Structural brain imaging of attention-deficit/hyperactivity disorder.
        Biol Psychiatry. 2004; 57: 1263-1272
        • Seidman L.J.
        • Faraone S.V.
        • Goldstein J.M.
        • Goodman J.M.
        • Kremen W.S.
        • Toomey R.
        • et al.
        Thalamic and amygdala-hippocampal volume reductions in first-degree relatives of patients with schizophrenia.
        Biol Psychiatry. 1999; 46: 941-954
        • Sergeant J.
        The cognitive-energetic model.
        Neurosci Biobehav Rev. 2000; 24: 7-12
        • Sergeant J.
        Modeling attention-defict/hyperactivity disorder.
        Biol Psychiatry. 2005; 57: 1248-1255
        • Sergeant J.A.
        • Geurts H.
        • Oosterlaan J.
        How specific is a deficit of executive functioning for attention-deficit/hyperactivity disorder?.
        Behav Brain Res. 2002; 130: 3-28
        • Sherman D.
        • Iacono W.
        • McGue M.
        Attention deficit hyperactivity disorder dimensions.
        J Am Acad Child Adolesc Psychiatry. 1997; 36: 745-753
        • Skuse D.H.
        Endophenotypes and child psychiatry.
        Br J Psychiatry. 2001; 178: 395-396
        • Slaats-Willemse D.
        • Swaab-Barneveld H.
        • de Sonneville L.
        • van der Meulen E.
        • Buitelaar J.
        Deficient response inhibition as a cognitive endophenotype of ADHD.
        J Am Acad Child and Adolesc Psychiatry. 2003; 42: 1242-1248
        • Solanto M.
        • Abikoff H.
        • Sonuga-Barke E.
        • Schachar R.
        • Logan G.
        • Wigal T.
        • et al.
        The ecological validity of delay aversion and response inhibition as measures of impulsivity in AD/HD.
        J Abnorm Child Psychol. 2001; 29: 215-228
        • Sonuga-Barke E.J.
        Psychological heterogeneity in AD/HD—a dual pathway model of behaviour and cognition.
        Behav Brain Res. 2002; 130: 29-36
        • Sonuga-Barke E.J.
        The dual pathway model of AD/HD.
        Neurosci Biobehav Rev. 2003; 27: 593-604
        • Sonuga-Barke E.J.
        Casual models of attention-deficit/hyperactivity disorder.
        Biol Psychiatry. 2005; 57: 1231-1238
        • Sonuga-Barke E.J.
        • Dalen L.
        • Remington B.
        Do executive deficits and delay aversion make independent contributions to preschool attention-deficit/hyperactivity disorder symptoms?.
        J Am Acad Child Adolesc Psychiatry. 2003; 42: 1335-1342
        • Sonuga-Barke E.J.
        • Williams E.
        • Hall M.
        • Saxton T.
        Hyperactivity and delay aversion. III: The effect on cognitive style of imposing delay after errors.
        J Child Psychol Psychiatry. 1996; 37: 189-194
        • Suarez B.K.
        • Hampe C.L.
        • Van Eerdewegh P.
        Problems of replicating linkage claims in psychiatry.
        in: Gershon E.S. Cloninger C.R. Barrett J.E. Genetic Approaches in Mental Disorders. American Psychiatric Press, Washington, DC1994: 23-46
        • Swanson J.
        • Oosterlaan J.
        • Murias M.
        • Schuck S.
        • Flodman P.
        • Spence M.A.
        • et al.
        Attention deficit/hyperactivity disorder children with a 7-repeat allele of the dopamine receptor D4 gene have extreme behavior but normal performance on critical neuropsychological tests of attention.
        Proc Natl Acad Sci U S A. 2000; 97: 4754-4759
        • Thompson P.M.
        • Cannon T.D.
        • Narr K.R.
        • van Erp T.
        • Poutanen V.-P.
        • Huttunen M.
        • et al.
        Genetic influences on brain structure.
        Nat Neurosci. 2001; 4: 1253-1258
        • Todd R.D.
        Genetics of attention deficit/hyperactivity disorder.
        Am J Med Genet (Neuropsychiatr Genet). 2000; 96: 241-243
        • Todd R.D.
        • Neuman R.J.
        • Lobos E.A.
        • Jong Y.J.
        • Reich W.
        • Heath A.C.
        Lack of association of dopamine D4 receptor gene polymorphisms with ADHD subtypes in a population sample of twins.
        Am J Med Genet (Neuropsychiatr Genet). 2001; 105: 432-438
        • Tsuang M.T.
        • Faraone S.V.
        The case for heterogeneity in the etiology of schizophrenia.
        Schizophr Res. 1995; 17: 161-175
        • van Beijsterveldt C.E.
        • van Baal G.C.
        Twin and family studies of the human electroencephalogram.
        Biol Psychol. 2002; 61: 111-138
        • Waldman I.D.
        • Rowe D.C.
        • Abramowitz A.
        • Kozel S.T.
        • Mohr J.H.
        • Sherman S.L.
        • et al.
        Association and linkage of the dopamine transporter gene and attention-deficit hyperactivity disorder in children.
        Am J Hum Genet. 1998; 63: 1767-1776
        • Willcutt E.G.
        • Doyle A.E.
        • Nigg J.T.
        • Faraone S.V.
        • Pennington B.F.
        Validity of the executive function theory of ADHD.
        Biol Psychiatry. 2005; 57: 1336-1346
        • Zametkin A.J.
        • Nordahl T.E.
        • Gross M.
        • King A.C.
        • Semple W.E.
        • Rumsey J.
        • et al.
        Cerebral glucose metabolism in adults with hyperactivity of childhood onset.
        N Eng J Med. 1990; 323: 1361-1366