Abstract
Endophenotypes are neurobiological markers cosegregating and associated with illness. These biomarkers represent a promising strategy to dissect ADHD biological causes. This study was aimed at contrasting the genetics of neuropsychological tasks for intelligence, attention, memory, visual-motor skills, and executive function in children from multigenerational and extended pedigrees that cluster ADHD in a genetic isolate. In a sample of 288 children and adolescents, 194 (67.4%) ADHD affected and 94 (32.6%) unaffected, a battery of neuropsychological tests was utilized to assess the association between genetic transmission and the ADHD phenotype. We found significant differences between affected and unaffected children in the WISC block design, PIQ and FSIQ, continuous vigilance, and visual-motor skills, and these variables exhibited a significant heritability. Given the association between these neuropsychological variables and ADHD, and also the high genetic component underlying their transmission in the studied pedigrees, we suggest that these variables be considered as potential cognitive endophenotypes suitable as quantitative trait loci (QTLs) in future studies of linkage and association.
Similar content being viewed by others
References
Arcos-Burgos M, Muenke M (2002) Genetics of population isolates. Clin Genet 61:233–247
Ardila A, Bernal B (2007) What can be localized in the brain? Toward a “factor” theory on brain organization of cognition. Int J Neurosci 117:935–969
Cabeza R, Nyberg L (2000) Imaging cognition II: an empirical review of 275 PET and fMRI studies. J Cogn Neurosci 12:1–47
Castellanos FX, Tannock R (2002) Neuroscience of attention-deficit hyperactivity disorder: the search for endophenotypes. Nat Rev Neurosci 3:617–628
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. J Abnorm Child Psychol 28:403–414
Clark C, Prior M, Kinsella G (2002) The relationship between executive function abilities, adaptive behaviour, and academic achievement in children with externalising behaviour problems. J Child Psychol Psychiat Allied Discipl 43:785–796
De Renzi E, Faglioni P (1978) Normative data and screening power of a shortened version of the token test. Cortex 14:41–49
Denckla MB (1996a) Biological correlates of learning and attention: what is relevant to learning disability and attention-deficit hyperactivity disorder? J Dev Behav Pediatr 17:114–119
Denckla MB (1996b) A theory and model of executive function. A neuropsychological perspective. In: Lyon GR, Krasnegor NA (eds) Attention, memory, and executive function. Baltimore, MD, Paul H. Brookes Publishing Co., pp 263–278
Doyle AE, Ferreira MA, Sklar PB, Lasky-Su J, Petty C, Fusillo SJ, Seidman LJ, Willcutt EG, Smoller JW, Purcell S, Biederman J, Faraone SV (2008) Multivariate genomewide linkage scan of neurocognitive traits and ADHD symptoms: suggestive linkage to 3q13. Am J Med Genet B Neuropsychiatr Genet 147B:1399–1411
Elston RC, Gray-McGuire C (2004) A review of the ‘statistical analysis for genetic epidemiology’ (SAGE) software package. Hum Genomics 1:456–459
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. J Abnorm Psychol 102:616–623
Fischer M, Barkley RA, Smallish L, Fletcher K (2005) Executive functioning in hyperactive children as young adults: attention, inhibition, response perseveration, and the impact of comorbidity. Dev Neuropsychol 27:107–133
Frazier TW, Demaree HA, Youngstrom EA (2004) Meta-analysis of intellectual and neuropsychological test performance in attention-deficit/hyperactivity disorder. Neuropsychol 18:543–555
Fristad MA, Cummins J, Verducci JS, Teare M, Weller EB, Weller RA (1998) Study IV: concurrent validity of the DSM-IV revised Children’s Interview for Psychiatric Syndromes (ChIPS). J Child Adolesc Psychopharmacol 8:227–236
Gottesman II, Gould TD (2003) The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry 160:636–645
Gottesman II, Shields J (1973) Genetic theorizing and schizophrenia. Br J Psychiatry 122:15–30
Heaton RK (1981) Wisconsin card sorting test (WCST). Manual Psychological Assessment Resources, Odessa, FL
Lezak MD (1994) Domains of behavior from a neuropsychological perspective: the whole story. Neb Symp Motiv 41:23–55
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? J Abnorm Psychol 114:216–222
Matier K, Wolf L, Halperin J (1994) The psychometric properties and clinical utility of a cancellation test in children. Dev Neuropsychol 10:165–177
Osterrieth PA (1944) Le teste de copie d’une figure complexe [The complex figure copy test]. Arch Psychol 30:206–256
Ostrosky-Solis F, Esther Gomez-Perez M, Matute E, Rosselli M, Ardila A, Pineda D (2007) NEUROPSI attention and memory: a neuropsychological test battery in Spanish with norms by age and educational level. Appl Neuropsychol 14:156–170
Palacio JD, Castellanos FX, Pineda DA, Lopera F, Arcos-Burgos M, Quiroz YT, Henao GC, Puerta IC, Ramirez DL, Rapoport JL, Bailey-Wilson J, Berg K, Muenke M (2004) Attention-deficit/hyperactivity disorder and comorbidities in 18 Paisa Colombian multigenerational families. J Am Acad Child Adolesc Psychiatry 43:1506–1515
Pineda D, Ardila A, Rosselli M (1999) Neuropsychological and behavioral assessment of ADHD in seven- to twelve-year-old children: a discriminant analysis. J Learn Disabil 32:159–173
Pineda DA, Puerta IC, Aguirre DC, Garcia-Barrera MA, Kamphaus RW (2007) The role of neuropsychologic tests in the diagnosis of attention deficit hyperactivity disorder. Pediatr Neurol 36:373–381
Quintana MI, Andreoli SB, Jorge MR, Gastal FL, Miranda CT (2004) The reliability of the Brazilian version of the composite international diagnostic interview (CIDI 2.1). Braz J Med Biol Res 37:1739–1745
Quintana MI, Gastal FL, Jorge MR, Miranda CT, Andreoli SB (2007) Validity and limitations of the Brazilian version of the composite international diagnostic interview (CIDI 2.1). Rev Bras Psiquiatr 29:18–22
Reich W (2000) Diagnostic interview for children and adolescents (DICA). J Am Acad Child Adolesc Psychiatry 39:59–66
Renou S, Hergueta T, Flament M, Mouren-Simeoni MC, Lecrubier Y (2004) Diagnostic structured interviews in child and adolescent’s psychiatry. Encephale 30:122–134
Rey A (1941) L’examen psychologique dans le cas d’encephalopathie traumatique. Arch Psychol 28:286–340
Rey A (1994) Test de copia de una figura compleja. TEA Ediciones, Madrid
Riccio CA, Hynd GW, Cohen MJ, Hall J, Molt L (1994) Comorbidity of central auditory processing disorder and attention-deficit hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 33:849–857
Rommelse NN, Arias-Vasquez A, Altink ME, Buschgens CJ, Fliers E, Asherson P, Faraone SV, Buitelaar JK, Sergeant JA, Oosterlaan J, Franke B (2008) Neuropsychological endophenotype approach to genome-wide linkage analysis identifies susceptibility loci for ADHD on 2q21.1 and 13q12.11. Am J Hum Genet 83:99–105
Rosselli M, Ardila A, Bateman JR, Guzman M (2001) Neuropsychological test scores, academic performance, and developmental disorders in Spanish-speaking children. Dev Neuropsychol 20:355–373
Rubio-Stipec M, Peters L, Andrews G (1999) Test-retest reliability of the computerized CIDI (CIDI-Auto): substance abuse modules. Subst Abus 20:263–272
Seidman LJ, Biederman J, Monuteaux MC, Weber W, Faraone SV (2000) Neuropsychological functioning in nonreferred siblings of children with attention deficit/hyperactivity disorder. J Abnorm Psychol 109:252–265
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? Dev Neuropsychol 27:79–105
Tannock R (1998) Etiology/risk factors for ADHD—cognitive and behavioral correlates. NIH consensus development conference on diagnosis and treatment of attention deficit hyperactivity disorder. William H. Natcher Conference Center, National Institutes of Health, Bethesda, MD
Wechsler D (1949) Wechsler intelligence scale for children. The Psychological Corporation, New York
Wechsler D (1974) Manual for the Wechsler intelligence scale for children—revised. The Psychological Corporation, New York
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. Biol Psychiatry 57:1336–1346
Acknowledgments
This research was funded by COLCIENCIAS, University of Antioquia, University of San Buenaventura and the NHGRI-NIH, who granted the Project: “Genética del Trastorno de Atención-Hiperactividad: los fenotipos complejos, los endofenotipos y la asociación con genes mayores y de susceptibilidad”. Code: 1115-04-18083, Contract: 459-2005.
Conflicts of interest
None to declare.
Author information
Authors and Affiliations
Corresponding authors
Rights and permissions
About this article
Cite this article
Pineda, D.A., Lopera, F., Puerta, I.C. et al. Potential cognitive endophenotypes in multigenerational families: segregating ADHD from a genetic isolate. ADHD Atten Def Hyp Disord 3, 291–299 (2011). https://doi.org/10.1007/s12402-011-0061-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12402-011-0061-3