The role of age in association analyses of ADHD and related neurocognitive functioning: A proof of concept for dopaminergic and serotonergic genes

American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics

Volumn 168, Issue 6, 2015, Pages 471-479

  Thissen, Andrieke J A M ^a,b   Bralten, Janita ^a,c   Rommelse, Nanda N J ^a,b   Arias Vasquez, Alejandro ^a,c   Greven, Corina U ^a,b,d   Heslenfeld, Dirk ^e   Luman, Marjolein ^e   Oosterlaan, Jaap ^e   Hoekstra, Pieter J ^f   Hartman, Catharina ^f   Franke, Barbara ^a,c   Buitelaar, Jan K ^a,b  

^a RADBOUD UNIVERSITY   (Netherlands)

^b RADBOUD UNIVERSITY NIJMEGEN   (Netherlands)

^c RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

^d KING'S COLLEGE LONDON   (United Kingdom)

^e VU UNIVERSITY AMSTERDAM   (Netherlands)

^f UNIVERSITY MEDICAL CENTER GRONINGEN   (Netherlands)

Author keywords

ADHD; Age; Dopamine; Neuropsychology; Serotonin

Indexed keywords

5 HTT GENE; ADOLESCENT; ADULT; AGE; ALLELE; ARTICLE; ATTENTION DEFICIT DISORDER; CHILD; COGNITION; CONTROLLED STUDY; DAT1 GENE; DRD4 GENE; FEMALE; GENE; GENE INTERACTION; GENETIC ASSOCIATION; GENETIC RISK; GENOTYPE PHENOTYPE CORRELATION; HOMOZYGOTE; HUMAN; INHIBITION (PSYCHOLOGY); MAJOR CLINICAL STUDY; MALE; MENTAL TASK; PRIORITY JOURNAL; RISK ASSESSMENT; RISK FACTOR; SYMPTOM; TASK PERFORMANCE; WORKING MEMORY; YOUNG ADULT;

EID: 84939562608     PISSN: 15524841     EISSN: 1552485X     Source Type: Journal    
DOI: 10.1002/ajmg.b.32290     Document Type: Article

References (80)

1. Altink ME, Rommelse NN, Slaats-Willemse DI, Vasquez AA, Franke B, Buschgens CJ, Fliers EA, Faraone SV, Sergeant JA, Oosterlaan J, et al. 2012. The dopamine receptor D4 7-repeat allele influences neurocognitive functioning, but this effect is moderated by age and ADHD status: an exploratory study. World J Biol Psychiatry 13(4):293-305.
2. Anderson DE, Bell TA, Awh E. 2012. Polymorphisms in the 5-HTTLPR gene mediate storage capacity of visual working memory. J Cogn Neurosci 24(5):1069-1076.
3. Azmitia EC. 2001. Modern views on an ancient chemical: serotonin effects on cell proliferation, maturation, and apoptosis. Brain Res Bull 56(5):413-424.
4. Banaschewski T, Becker K, Scherag S, Franke B, Coghill D. 2010. Molecular genetics of attention-deficit/hyperactivity disorder: An overview. Eur Child Adolesc Psychiatry 19(3):237-257.
5. Beitchman JH, Davidge KM, Kennedy JL, Atkinson L, Lee V, Shapiro S, Douglas L. 2003. The serotonin transporter gene in aggressive children with and without ADHD and nonaggressive matched controls. Ann N Y Acad Sci 1008:248-251.
6. Bellgrove MA, Hawi Z, Kirley A, Gill M, Robertson IH. 2005. Dissecting the attention deficit hyperactivity disorder (ADHD) phenotype: sustained attention, response variability and spatial attentional asymmetries in relation to dopamine transporter (DAT1) genotype. Neuropsychologia 43(13):1847-1857.
7. Biederman J, Mick E, Faraone SV. 2000. Age-dependent decline of symptoms of attention deficit hyperactivity disorder: Impact of remission definition and symptom type. Am J Psychiatry 157(5):816-818.
8. Boomsma D, Busjahn A, Peltonen L. 2002. Classical twin studies and beyond. Nat Rev Genet 3(11):872-882.
9. Boonstra AM, Kooij JJ, Buitelaar JK, Oosterlaan J, Sergeant JA, Heister JG, Franke B. 2008. An exploratory study of the relationship between four candidate genes and neurocognitive performance in adult ADHD. Am J Med Genet B Neuropsychiatr Genet 147(3):397-402.
10. Brookes K, Xu X, Chen W, Zhou K, Neale B, Lowe N, Anney R, Franke B, Gill M, Ebstein R, et al. 2006. The analysis of 51 genes in DSM-IV combined type attention deficit hyperactivity disorder: Association signals in DRD4, DAT1 and 16 other genes. Mol Psychiatry 11(10):934-953.
11. Carrasco X, Rothhammer P, Moraga M, Henríquez H, Chakraborty R, Aboitiz F, Rothhammer F. 2006. Genotypic interaction between DRD4 and DAT1 loci is a high risk factor for attention-deficit/hyperactivity disorder in Chilean families. Am J Med Genet B Neuropsychiatr Genet. 141B(1):51-54.
12. Castellanos FX, Tannock R. 2002. Neuroscience of attention-deficit/hyperactivity disorder: the search for endophenotypes. Nat Rev Neurosci 3(8):617-628.
13. Coghill DR, Hayward D, Rhodes SM, Grimmer C, Mathhews K. 2014. A longitudinal examantion of neuropsychological and clinical functioning in boys with attention deficit hyperactivity disorder (ADHD): Improvements in executive functioning do not explain clinical improvement. Psychol Med. 44(5):1087-1099.
14. Congdon E, Lesch KP, Canli T. 2008. Analysis of DRD4 and DAT polymorphisms and behavioral inhibition in healthy adults: Implications for impulsivity. Am J Med Genet B Neuropsychiatr Genet 147B(1):27-32.
15. Conners CK, Erhardt D, Sparrow EP. 1999. Conner's Adult ADHD Rating Scales: CAARS. North Tonawanda, NY: Multi-Health Systems.
16. Crosbie J, Arnold P, Paterson A, Swanson J, Dupuis A, Li X, Shan J, Goodale T, Tam C, Strug LJ, et al. 2013. Response inhibition and ADHD traits: Correlates and heritability in a community sample. J Abnormal Child Psychol 41(3):497-507.
17. Crosbie J, Perusse D, Barr CL, Schachar RJ. 2008. Validating psychiatric endophenotypes: Inhibitory control and attention deficit hyperactivity disorder. Neurosci Biobehav Rev 32(1):40-55.
18. Del Campo N, Chamberlain SR, Sahakian BJ, Robbins TW. 2011. The roles of dopamine and noradrenaline in the pathophysiology and treatment of attention-deficit/hyperactivity disorder. Biol Psychiatry 69(12):e145-e157.
19. DSM-5 A . 2013. Diagnostic and statistical manual of mental health disorders: DSM-5. 5th ed.. Washington, DC: American Psychiatric Publishing.
20. Durston S, Fossella JA, Casey BJ, Hulshoff Pol, Galvan HE, Schnack A, Steenhuis HG, Minderaa MP, Buitelaar RB, Kahn JK, et al. 2005. Differential effects of DRD4 and DAT1 genotype on fronto-striatal gray matter volumes in a sample of subjects with attention deficit hyperactivity disorder, their unaffected siblings, and controls. Mol Psychiatry 10(7):678-685.
21. Elia J, Devoto M. 2007. ADHD genetics: 2007 update. Curr Psychiatry Rep 9(5):434-439.
22. Faraone SV, Buitelaar J. 2010. Comparing the efficacy of stimulants for ADHD in children and adolescents using meta-analysis. Eur Child Adolesc Psychiatry 19(4):353-364.
23. Faraone SV, Perlis RH, Doyle AE, Smoller JW, Goralnick JJ, Holmgren MA, Sklar P. 2005. Molecular genetics of attention-deficit/hyperactivity disorder. Biol Psychiatry 57(11):1313-1323.
24. Franke B, Faraone SV, Asherson P, Buitelaar J, Bau CH, Ramos-Quiroga JA, Mick E, Grevet EH, Johansson S, Haavik J, et al. 2012. The genetics of attention deficit/hyperactivity disorder in adults, a review. Mol Psychiatry 17(10):960-987.
25. Franke B, Hoogman M, Arias Vasquez, Heister A, Savelkoul JG, Naber PJ, Scheffer M, Kiemeney H, Kan LA, Kooij CC. 2008. Association of the dopamine transporter (SLC6A3/DAT1) gene 9-6 haplotype with adult ADHD. Am J Med Genet B Neuropsychiatr Genet 147B(8):1576-1579.
26. Franke B, Vasquez AA, Johansson S, Hoogman M, Romanos J, Boreatti-Hummer A, Heine M, Jacob CP, Lesch KP, Casas M, et al. 2010. Multicenter analysis of the SLC6A3/DAT1 VNTR haplotype in persistent ADHD suggests differential involvement of the gene in childhood and persistent ADHD. Neuropsychopharmacology 35(3):656-664.
27. Frazier-Wood AC, Bralten J, Arias-Vasquez A, Luman M, Ooterlaan J, Sergeant J, Faraone SV, Buitelaar J, Franke B, Kuntsi J, et al. 2012. Neuropsychological intra-individual variability explains unique genetic variance of ADHD and shows suggestive linkage to chromosomes 12, 13, and 17. Am J Med Genet B Neuropsychiatr Genet 159B(2):131-140.
28. Froehlich TE, Lanphear BP, Dietrich KN, Cory-Slechta DA, Wang N, Kahn RS. 2007. Interactive effects of a DRD4 polymorphism, lead, and sex on executive functions in children. Biol Psychiatry 62(3):243-249.
29. Gabriela ML, John DG, Magdalena BV, Ariadna GS, Francisco de LP, Liz SM, Lino PC, Josefina RG, Ernesto RZ, Carlos CF. 2009. Genetic interaction analysis for DRD4 and DAT1 genes in a group of Mexican ADHD patients. Neurosci Lett. 451(3):257-260.
30. Gizer IR, Ficks C, Waldman ID. 2009. Candidate gene studies of ADHD: A meta-analytic review. Human genetics 126(1):51-90.
31. Gottesman II, Gould TD. 2003. The endophenotype concept in psychiatry: Etymology and strategic intentions. Am J Psychiatry 160(4):636-645.
32. Greven CU, Asherson P, Rijsdijk FV, Plomin R. 2011. A longitudinal twin study on the association between inattentive and hyperactive-impulsive ADHD symptoms. J Abnorm Child Psychol 39(5):623-632.
33. Johansson S, Halleland H, Halmoy A, Jacobsen KK, Landaas ET, Dramsdahl M, Fasmer OB, Bergsholm P, Lundervold AJ, Gillberg C, et al. 2008. Genetic analyses of dopamine related genes in adult ADHD patients suggest an association with the DRD5-microsatellite repeat, but not with DRD4 or SLC6A3 VNTRs. Am J Med Genet B Neuropsychiatr Genet 147B(8):1470-1475.
34. Kasper LJ, Alderson RM, Hudec KL. 2012. Moderators of working memory deficits in children with attention-deficit/hyperactivity disorder (ADHD): A meta-analytic review. Clin Psychol Rev 32(7):605-617.
35. 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. J Am Acad Child Adolesc Psychiatry 36(7):980-988.
36. Kebir O, Tabbane K, Sengupta S, Joober R. 2009. Candidate genes and neuropsychological phenotypes in children with ADHD: Review of association studies. J Psychiatry Neurosci 34(2):88-101.
37. Klein C, Wendling K, Huettner P, Ruder H, Peper M. 2006. Intra-subject variability in attention-deficit hyperactivity disorder. Biol Psychiatry 60(10):1088-1097.
38. Kuntsi J, Pinto R, Price TS, van der Meere JJ, Frazier-Wood AC, Asherson P. 2013. The separation of ADHD inattention and hyperactivity-impulsivity symptoms: Pathways from genetic effects to cognitive impairments and symptoms. J Abnorm Child Psychol 42(1):127-136.
39. Landaas ET, Johansson S, Jacobsen KK, Ribases M, Bosch R, Sanchez-Mora C, Jacob CP, Boreatti-Hummer A, Kreiker S, Lesch KP, et al. 2010. An international multicenter association study of the serotonin transporter gene in persistent ADHD. Genes Brain Behav 9(5):449-458.
40. Lane HY, Liu YC, Huang CL, Hsieh CL, Chang YL, Chang L, Chang YC, Chang WH. 2008. Prefrontal executive function and D1, D3, 5-HT2A and 5-HT6 receptor gene variations in healthy adults. J Psychiatry Neurosci 33(1):47-53.
41. Larsson H, Lichtenstein P, Larsson JO. 2006. Genetic contributions to the development of ADHD subtypes from childhood to adolescence. J Am Acad Child Adolesc Psychiatry 45(8):973-981.
42. Larsson JO, Larsson H, Lichtenstein P. 2004. Genetic and environmental contributions to stability and change of ADHD symptoms between 8 and 13 years of age: A longitudinal twin study. J Am Acad Child Adolesc Psychiatry 43(10):1267-1275.
43. Lesch KP, Bengel D, Heils A, Sabol SZ, Greenberg BD, Petri S, Benjamin J, Muller CR, Hamer DH, Murphy DL. 1996. Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 274(5292):1527-1531.
44. Leth-Steensen C, Elbaz ZK, Douglas VI. 2000. Mean response times, variability, and skew in the responding of ADHD children: A response time distributional approach. Acta Psychol (Amst) 104(2):167-190.
45. Li D, Sham PC, Owen MJ, He L. 2006. Meta-analysis shows significant association between dopamine system genes and attention deficit hyperactivity disorder (ADHD). Hum Mol Genet 15(14):2276-2284.
46. Li J, Ji L. 2005. Adjusting multiple testing in multilocus analyses using the eigenvalues of a correlation matrix. Heredity (Edinb) 95(3):221-227.
47. Martinussen R, Hayden J, Hogg-Johnson S, Tannock R. 2005. A meta-analysis of working memory impairments in children with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 44(4):377-384.
48. Muglia P, Jain U, Macciardi F, Kennedy JL. 2000. Adult attention deficit hyperactivity disorder and the dopamine D4 receptor gene. Am J Med Genet 96(3):273-277.
49. 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. J Abnorm Child Psychol 37(3):443-453.
50. Noreika V, Falter CM, Rubia K. 2013. Timing deficits in attention-deficit/hyperactivity disorder (ADHD): Evidence from neurocognitive and neuroimaging studies. Neuropsychologia 51(2):235-266.
51. Nyholt DR. 2004. A simple correction for multiple testing for single-nucleotide polymorphisms in linkage disequilibrium with each other. Am J Hum Genet 74(4):765-769.
52. Oades RD. 2007. Role of the serotonin system in ADHD: Treatment implications. Expert Rev Neurother 7(10):1357-1374.
53. Oades RD. 2008. Dopamine-serotonin interactions in attention-deficit hyperactivity disorder (ADHD). Prog Brain Res 172:543-565.
54. Paaver M, Nordquist N, Parik J, Harro M, Oreland L, Harro J. 2007. Platelet MAO activity and the 5-HTT gene promoter polymorphism are associated with impulsivity and cognitive style in visual information processing. Psychopharmacology (Berl) 194(4):545-554.
55. Plomin R, Spinath FM. 2004. Intelligence: Genetics, genes, and genomics. J Pers Soc Psychol 86(1):112-129.
56. Poelmans G, Pauls DL, Buitelaar JK, Franke B. 2011. Integrated genome-wide association study findings: Identification of a neurodevelopmental network for attention deficit hyperactivity disorder. Am J Psychiatry 168(4):365-377.
57. Polanczyk G, de Lima MS, Horta BL, Biederman J, Rohde LA. 2007. The worldwide prevalence of ADHD: A systematic review and metaregression analysis. Am J Psychiatry 164(6):942-948.
58. Polderman TJ, Posthuma D, De Sonneville LM, Stins JF, Verhulst FC, Boomsma DI. 2007. Genetic analyses of the stability of executive functioning during childhood. Biol Psychol 76(1-2):11-20.
59. Rommelse N, Altink M, Oosterlaan J, Beem L, Buschgens C, Buitelaar J, Sergeant J. 2008a. Speed, variability, and timing of motor output in ADHD: which measures are useful for endophenotypic research. Behav Genet 38(2):121-132. Epub 2007 Dec 11.
60. Rommelse NN. 2008. Endophenotypes in the genetic research of ADHD over the last decade: Have they lived up to their expectations. Expert Rev Neurother 8(10):1425-1429.
61. Rommelse NN, Altink ME, Arias-Vasquez A, Buschgens CJ, Fliers E, Faraone SV, Buitelaar JK, Sergeant JA, Franke B, Oosterlaan J. 2008b. A review and analysis of the relationship between neuropsychological measures and DAT1 in ADHD. Am J Med Genet B Neuropsychiatr Genet 147B(8):1536-1546.
62. Rommelse NN, Altink ME, Oosterlaan J, Buschgens CJ, Buitelaar J, Sergeant JA. 2008c. Support for an independent familial segregation of executive and intelligence endophenotypes in ADHD families. Psychol Med 38(11):1595-1606.
63. Schaid DJ, Rowland CM, Tines DE, Jacobson RM, Poland GA. 2002. Score tests for association between traits and haplotypes when linkage phase is ambiguous. Am J Hum Genet 70(2):425-434.
64. Seidman LJ. 2006. Neuropsychological functioning in people with ADHD across the lifespan. Clin Psychol Rev 26(4):466-485.
65. Shaw P, Gornick M, Lerch J, Addington A, Seal J, Greenstein D, Sharp W, Evans A, Giedd JN, Castellanos FX, et al. 2007. Polymorphisms of the dopamine D4 receptor, clinical outcome, and cortical structure in attention-deficit/hyperactivity disorder. Arch Gen Psychiatry 64(8):921-931.
66. Shaw P, Lerch J, Greenstein D, Sharp W, Clasen L, Evans A, Giedd J, Castellanos FX, Rapoport J. 2006. Longitudinal mapping of cortical thickness and clinical outcome in children and adolescents with attention-deficit/hyperactivity disorder. Arch Gen Psychiatry 63(5):540-549.
67. Soderqvist S, Bergman Nutley, Peyrard-Janvid S, Matsson M, Humphreys H, Kere K, Klingberg J. 2012. Dopamine, working memory, and training induced plasticity: Implications for developmental research. Dev Psychol 48(3):836-843.
68. Spencer TJ, Biederman J, Madras BK, Faraone SV, Dougherty DD, Bonab AA, Fischman AJ. 2005. In vivo neuroreceptor imaging in attention-deficit/hyperactivity disorder: A focus on the dopamine transporter. Biol Psychiatry 57(11):1293-1300.
69. Thapar A, Cooper M, Eyre O, Langley K. 2013. What have we learnt about the causes of ADHD. J Child Psychol Psychiatry 54(1):3-16.
70. Thissen AJ, Rommelse NN, Hoekstra PJ, Hartman C, Heslenfeld D, Luman M, van Lieshout M, Franke B, Oosterlaan J, Buitelaar JK. 2014a. Attention deficit hyperactivity disorder (ADHD) and executive functioning in affected and unaffected adolescents and their parents: Challenging the endophenotype construct. Psychol Med 44(4):881-892.
71. Thissen AJAM, Luman M, Hartman C, Hoekstra P, van Lieshout M, Franke B, Oosterlaan J, Rommelse NNJ, Buitelaar JK. 2014b. ADHD and motor timing in adolescents and their parents: Familial characteristics of reaction time variability vary with age. Am Acad Child Adolesc Psychiatry 53:1010-1019.
72. Toplak ME, Dockstader C, Tannock R. 2006. Temporal information processing in ADHD: Findings to date and new methods. J Neurosci Methods 151(1):15-29.
73. Turgay A, Goodman DW, Asherson P, Lasser RA, Babcock TF, Pucci ML, Barkley R, Group ATPMW. 2012. Lifespan persistence of ADHD: the life transition model and its application. J Clin Psychiatry 73(2):192-201.
74. Volkow ND, Fowler JS, Wang GJ, Ding YS, Gatley SJ. 2002. Role of dopamine in the therapeutic and reinforcing effects of methylphenidate in humans: Results from imaging studies. Eur Neuropsychopharmacol 12(6):557-566.
75. von Rhein D, Mennes M, van Ewijk H, Groenman AP, Zwiers MP, Oosterlaan J, Heslenfeld D, Franke B, Hoekstra PJ, Faraone SV, Hartman C, Buitelaar JK. 2014. The NeuroIMAGE study: A prospective phenotypic, cognitive, genetic and MRI study in children with attention-deficit hyperactivity disorder. Design Descriptives European Child and Adolescent Psychiatry. Epub ahead of print.
76. Wiggins JL, Bedoyan JK, Carrasco M, Swartz JR, Martin DM, Monk CS. 2014. Age-related effect of serotonin transporter genotype on amygdala and prefrontal cortex function in adolescence. Hum Brain Mapp 35(2):646-658.
77. 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(11):1336-1346.
78. Wu J, Xiao H, Sun H, Zou L, Zhu LQ. 2012. Role of dopamine receptors in ADHD: A systematic meta-analysis. Mol Neurobiol 45(3):605-620.
79. Xu X, Hawi Z, Brookes KJ, Anney R, Bellgrove M, Franke B, Barry E, Chen W, Kuntsi J, Banaschewski T, et al. 2008. Replication of a rare protective allele in the noradrenaline transporter gene and ADHD. Am J Med Genet B Neuropsychiatr Genet 147B(8):1564-1567.
80. Zilles D, Meyer J, Schneider-Axmann T, Ekawardhani S, Gruber E, Falkai P, Gruber O. 2012. Genetic polymorphisms of 5-HTT and DAT but not COMT differentially affect verbal and visuospatial working memory functioning. Eur Arch Psychiatry Clin Neurosci 262(8):667-676.