Alteraciones genéticas en el trastorno por déficit de atención con hiperactividad: relación con variables neuropsicológicas
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2011-03-30
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González-Pérez, P. A., Hernández Expósito, S., Martín González, R., & García Quintás, A. (2011). Alteraciones genéticas en el trastorno por déficit de atención con hiperactividad: relación con variables neuropsicológicas. Revista De Psiquiatría Infanto-Juvenil, 28(1), 51–62. Recuperado a partir de https://aepnya.eu/index.php/revistaaepnya/article/view/179
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Artículo de revisión
Palabras clave:
Atención, funciones ejecutivas, genes, neuropsicología infantil, neurotransmisores, TDAHResumen
El Trastorno por Déficit de Atención con Hiperactividad (TDAH) es una patología frecuente de la infancia con una fuerte contribución genética. Tras unos años dedicados al estudio de los genes específicos que explicaban la sintomatología nuclear del trastorno (inatención, hiperactividad e impulsividad), en la actualidad el interés de los investigadores se ha ampliado, considerando la repercusión neuropsicológica que estas alteraciones genéticas tienen en los sujetos afectos de esta patología. En este trabajo revisamos la literatura existente sobre los correlatos genéticos de los déficits cognitivos del TDAH. Estas nuevas estrategias de investigación, necesariamente multidisciplinares, pretenden conseguir, además del incremento en la caracterización neurobiológica de esta patología, líneas de tratamiento alternativas a las existentes que respondan a la relación comentada entre genes y cognición en el TDAH.
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2. Asociación de Psiquiatría Americana Manual Diagnóstico y Estadístico de los Trastornos Mentales (DSM-IV-TR). Barcelona: Masson. 2002.
3. Silver LB. Trastorno por déficit de Atención con Hiperactividad, guía clínica de diagnóstico y tratamiento para profesionales de la salud. Barcelona: Psiquiatría Editores. 2004.
4. Wilens TE, Biederman J, Spencer TJ . Attention deficit/hyperactivity disorder across the lifespan. Ann Rev Med 2002; 53:112131.
5. Curatolo P, Paloscia C, D’Agati E, Moavero R, Pasini A. The neurobiology of attention deficit/hyperactivity disorder. Eur J Paediatr Neurol 2009; 299-304.
6. Waldman ID, Rhee SH. Behavioral and molecular genetic studies of ADHD. En: Sandberg S. Hyperactivity and attention disorder in childhood. 2nd ed. New York: Cambridge University Press. 2002. 290-335.
7. Faraone SV, Perlis RH, Doyle AE, Smoller JW, Goralnick JJ, Holmgren MA et al. Molecular genetics of attention-deficit/hyperactivity disorder. Biol Psychiatry 2005; 57: 1313-1323.
8. Biederman J, Faraone SV. Attention-deficit hyperactivity disorder. Lancet 2005; 366: 237-48.
9. Bellgrove MA, Hawi Z, Kirley A. Dissecting the attention deficit hyperactivity disorder (ADHD) phenotype: sustained attention, response variability and spatial attentional asymmetries in relation to dopamine transporter (DAT1) genotype. Neuropsychologia 2005; 43: 1847-57.
10. Nigg JT. Is ADHD an inhibitory disorder? Psychol Bull 2001; 127: 571-589.
11. Giros B, Mestikawy S, Godinot N, Zheng K, Han H, Yang-feng T et al. Cloning, pharmacological characterization, and chromosome assignment of the human dopamine transporter. Mol Pharmacol 1992. 42: 38390.
12. Vandenberg DJ, Persico AM, Hawkins AL, Griffin CA, Li X, Jabs EW et al. Human dopamine transporter gene maps to chromosome 5p15.3 and displays a VNTR. Genomics 1992; 14: 1104-6.
13. Doucette-Stamm LA, Blakely DJ, Tian J, Mockus S, Mao JI. Population genetic study of the human dopamine transporter gene (DAT1). Genet Epidemiol 1995; 12: 303– 308.
14. Mill J, Asherson P, Browes C, D´Souza U, Craig I. Expression of the dopamine transporter genes is regulated by 3´-UTR VNTR: evidence from brain and lymphocytes using quantitative RT-PCR. Am J Med Gen 2002; 114: 975-979.
15. Volkow N, Ding Y, Fowler J, Wang G, Logan J, Gatley J et al. Is methylphenidate like cocaine? Arch Gen Psychiatry 1995; 52: 456–463.
16. Rommelse N, Altink M, Arias-Vazquez A, Buschgens C, Fliers E, Faraone S et al. A review and analysis of the relationship between neuropsychological measures and DAT1 in ADHD. Am J Med Gen 2008; 147B: 1536-1546.
17. Loo SK, Specter E, Smolen A, Hopfer C, Teale PD, Reite ML. Functional effects of the DAT1 polymorphism on EEG measures in ADHD. J Am Acad Child Adolesc Psychiatry 2003; 42: 986-93.
18. Oh KS, Shin DW, Oh GT, Noh KS. Dopamine transporter genotype influences the attention deficit in Korean boys with ADHD. Yonsei Med J 2003; 44: 787-92.
19. Karama S, Grizenko N, Sonuga-Barke E, Doyle A, Biederman J, Mbekou V et al. Dopamine transporter 3?UTR VNTR genotype is a marker of performance on executive function tasks in children with ADHD. BMC Psychiatry 2008; 8:b45.
20. Mill J, Caspi A, Williams BS, Craig I, Taylor A, Polo-Tomas M et al. Prediction of heterogeneity in intelligence and adult prognosis by geneticpolymorphisms in the dopamine system among children with attention-deficit/hyperactivity disorder. Arch Gen Psychiatry 2006; 63: 462-469.
21. Sonuga-Barke EJS, Brookes KJ, Buitelaar J, Anney R, Bitsakou P, Baeyens D et al. Intelligence in DSM-IV combined type attention-deficit/hyperactivity disorder is not predicted by either dopamine receptor/ transporter genes or other previously identified risk alleles for attention-deficit/hyperactivity disorder. Am J Med Genet B Neuropsychiatr Genet 2008; 147: 316–9.
22. Genro JP, Roman T, Zeni CP, Grevet EH, Schmitz M, de Abreu PB et al. No association between dopaminergic polymorphisms and intelligence variability in attention-deficit/hyperactivity disorder. Mol Psychiatry 2006; 11: 1066–1067.
23. Rueda MR, Rothbart MK, McCandliss BD, Saccomanno L, Posner MI. Training, maturation, and genetic influences on the development of executive attention. Proc Natl Acad Sci USA 2005; 102: 14931–14936.
24. Eubanks JH, Djabali M, Selleri L, Grandy DK, Civelli O, McElligot DL et al. Structure and linkage of the D2 dopamine receptor and neural cell adhesion molecule genes on human chromosome 11q23. Genomics 1992; 14: 1010-1018.
25. Usiello A, Baik JH, Rouge-Pont F, Picetti R, Dierich A, Lemeur M et al. Distinct functions of the two isoforms of dopamine D2 receptors. Nature 2000; 408: 199-203.
26. Comings DE, Comings DG, Muhleman D, Dietz G, Shahbahrami B, Tast D et al. The dopamine D2 receptor locus as a modifying gene in neuropsychiatric disorder. JAMA 1991; 266: 1793-1800.
27. Le Coniat M, Sokoloff P, Hillion J, Martres MP, Giros B, Pilon C et al. Chromosomal localization of the human D3 dopamine receptor gene. Human Genetic 1991; 87: 618620.
28. Barr CL, Wig KG, Wu j, Zai C, Bloom s, Tannock R et al. Linkage study of two polymorphisms at the dopamine D3 receptor gene and attention-deficit hyperactivity disorder. Am Journal Med Genet 2000; 96: 114-117.
29. Kopeckova M, Paclt I, Petrasek J, Pacltova D, Malikova M, Zagatova V. Some ADHD polymorphisms (in genes DAT1, DRD2, DRD3, DBH, 5-HTT) in case-control study of 100 subjects 6-10 age. Neuroendocrinol Let 2008; 29: 246-251.
30. Guan L, Wang B, Chen Y, Yang L, Li J, Qian Q et al. A high-density single-nucleotide polymorphism screen of 23 candidate genes in attention deficit hyperactivity disorder: suggesting multiple susceptibility genes among Chinese Han population. Mol Psychiatry 2008; 14: 546-554.
31. LaHoste GJ, Swanson JM, Wigal SB, Glabe C, King N, Kennedy JL. Dopamine D4 receptor gene polymorphism is associated with attention deficit hyperactivity disorder. Molecular Psychiatry 1996; 1: 121-124.
32. Faraone SV. Report from the second international meeting of the attention deficit hyperactivity disorder molecular genetic network. American Journal of Medical Genetics 2001; 105: 255-258.
33. Sherrington R, Mankoo B, Attwood J, Kalsi G, Curtis D, Buetow K et al. Cloning of the human dopamine D5 receptor gene and identification of a highly polymorphic microsatellite for the DRD5 locus that shows tight linkage to the chromosome 4p reference marker RAF1P1. Genomics 1993; 18: 423-425.
34. Lowe N, Kirley A, Hawi Z, Sham P, Wickham H, Kratochvil CJ et al. Joint analysis of DRD5 marker concludes association with ADHD confined to the predominantly inattentive and combined subtypes. Am J Hum Genet 2004; 74: 348-356.
35. Lachman HM, Papolos DF, Saito T, Yu YM, Szumlanski CL, Weinshilboum RM. Human cathecol-O-methyltransferase pharmacogenetics: description of a functional polymorphism and its potential application to neuropsychiatric disorders. Pharmacogenetics 1996; 6: 243-250.
36. Mills S, Langley K, Van den Bree M, Street E, Turic D, Owen MJ et al. No evidence of association between cathecol-O-methyltransferase (COMT) Val158Met genotype and performance on neuropsychological tasks in children with ADHD: a case-control study. BMC Psychiatry 2004; 4: 15.
37. Taerk E, Grizenko N, Ben Amor L, Lageix P, Mbekou V, Deguzman R et al. Cathecol-Omethyltransferase (COMT) Val108/158Met polymorphism does not modulate executive function in children with ADHD. BMC Med Genet 2004; 5: 30.
38. Eisenberg J, Mei-Tal G, Steinberg A, Tartakovsky E, Zohar A, Gritsenko I et al. Halotype relative risk study of cathecol-Omethyltransferase (COMT) and attention déficit hyperactivity disorer (ADHD): association of the high enzyme activity Val allele with ADHD impulsive-hyperactive phenotype. Am Journal Med Genet 1999; 88: 497-502.
39. Craig Sp, Buckle VJ, Lamouroux A, Mallet J, Craig IW. Localization of human dopamine beta hydroxylase (DBH) gene to chromosome 9q34. Cytogenet Cell Genet 1988; 48: 48-50.
40. DiMaio S, Grizenko N, Joober R. Dopamine genes and attention-deficit hyperactivity disorder: A review. J. Psychiarty Neurosci 2003; 28: 27-38.
41. Bellgrove MA, Mattingley JB, Hawi Z, Mullins C, Kirley A, Gill M et al. Impaired temporal resolution of visual attention and dopamine beta hydroxylase genotype in attention-deficit/hyperactivity disorder. Biological Psychiatry 2006; 60: 1039-1045.
42. Bellgrove MA, Hawi Z, Gill M, Robertson IH. The cognitive genetics of attention deficit hyperactivity disorder (ADHD): sustained attention as a candidate phenotype. Cortex 2006; 42: 838-845.
43. Barkley RA, Smith KM, Fisher M, Navia B. An examination of the behavioral and neuropsychological correlates of three ADHD candidate gene polymorphisms (DRD47+, DBH Taq1 A2, and DAT1 40 bp VNRT) in hyperactive and normal children followed to adulthood. Am Journal Medical Genetic B Neuropsychiatric Genet 2006; 141B: 487-498.
44. Lan NC, Heinzmann C, Gal A, Klisak I, Orth U, Lai E et al. Human monoamine oxidase A and B genes map to Xp 11.23 and are deleted in a patient with Norrie disease. Genomics 1989; 4: 552–559.
45. Deckert J, Catalano M, Syagalio YV, Bosi M, Oklandnova O, Di Bella D et al. Excess of high activity monoamine oxidase. A gene promoter alleles in female patients with panic disorder. Human Molecular Genetic 1999; 8: 621-624.
46. Manuck SB, Flory JD, Ferrell RE, Mann JJ, Muldoon MF. A regulatory polymorphism of the monoamine oxidase-A gene may be associated with variability in aggression, impulsivity, and central nervous system serotonergic responsivity. Psychiatry Research 2000; 95: 9-23.
47. Manor I, Tyano S, Mel E, Eisenberg J, Bachner-Melman R, Kotler M et al. Familybased and association studies of monoamine oxidase A and attention déficit hyperactivity disorder (ADHD): preferential transmission of the long promoter-region repeat and its association with impaired performance on a continuos performance test (TOVA). Molecular Psychiatry 2002; 7: 626-632.
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