Views
7 months ago

Genética del trastorno por déficit de atención e hiperactividad. r. José Alberto Angemi.

  • Text
  • Bibliotecascienscomar
  • Angemi
  • Factores
  • Receptor
  • Estudio
  • Trastorno
  • Estudios
  • Disorder
  • Adhd
  • Riesgo
  • Genes
  • Tdah
La etiología del TDAH es compleja y multifactorial. La teoría más plausible hasta la fecha es que surge de múltiples factores de riesgo genéticos y ambientales, que tienen pequeños efectos individuales y actúan en conjunto para aumentar la susceptibilidad a desarrollar el trastorno. Esto constituye un patrón de herencia no mendeliana, compleja, con posible penetrancia incompleta y expresividad variable, que sugiere la acción conjunta de múltiples genes de efecto moderado o discreto con factores ambientales. En este artículo se realiza una revisión narrativa del tema, teniendo en cuenta la descripción de genes candidatos y estudio de transcriptomas y GWAS.

Psicofarmacología

Psicofarmacología 24:135, mayo de 2024 Referencias bibliográficas • 1. Angemi J (2017). Diagnóstico y tratamiento del trastorno por déficit de atención e hiperactividad. En PROAPSI (Programa de actualización en psiquiatría) Barembaum R et al. Bs As. Ed. Médica Panamericana. • 2. Nikolas M, Burt S.A. (2010). Genetic and environmental influ- ences on ADHD symptom dimensions of inattention and hyper- activity: a meta-analysis. J. Abnorm. Psychol. 119 (1), 1. • 3. Faraone S, Larsson H (2019). Genetics of attention deficit hyperactivity disorder. Mol. Psychiatry 24 (4), 562–575. • 4. Levy F, Hay D, Mc Stephen M, Wood C, Waldman I (1997). Attention-deficit hyperactivity disorder: a category or a continuum? Genetic analysis of a large-scale twin study. J. Am. Acad. Child Adolesc. Psychiatry 36, 737–744. • 5. Sprich S, Biederman J, Crawford H, Mundy E, Faraone S. (2000). Adoptive and biological families of children and adolescents with ADHD. J Am Acad Child Adolesc Psychiatry; 39:1432–7. • 6. McLoughlin G, Ronald A, Kuntsi J, Asherson P, Plomin R. (2007). Genetic support for the dual nature of attention deficit hyperactivity disorder: substantial genetic overlap between the inattentive and hyperactive-impulsive components. J Abnorm Child Psychol; 35:999–1008. • 7. Pettersson E, Anckarsater H, Gillberg C, Lichtenstein P. Different neurodevelopmental symptoms have a common genetic etiology. (2013) J Child Psychol Psychiatry; 54:1356–65. • 8. Cabana-Dominguez J, Anton-Galindo E, Fernandez- Castillo N, Singgih E, O’Leary A, Norton W et al (2023) The translational genetics of ADHD and related phenotypes in model organisms. Neuroscience and Biobehavioral Reviews 144 (2023) 104949. • 9. Matrisciano F, Tueting P, Dalal I, Kadriu B, Grayson D, Davis J et al. (2013). Epigenetic modifications of GABAergic interneurons are associated with the schizophrenia-like phenotype induced by prenatal stress in mice. Neuropharmacology 68, 184–194. • 10. Hawi Z, Cummin, T, Tong J, Johnson B, Lau R, Samarrai W, Bellgrove M (2015). The molecular genetic architecture of attention deficit hyperactivity disorder. Mol. Psychiatry 20 (3), 289–297. • 11. Klein M, Onnink M, van Donkelaar M, Thomas Wolfers T, Harich B, Shi Y et al (2017). Brain imaging genetics in ADHD and beyond – Mapping pathways from gene to disorder at different levels of complexity. Neuroscience and Biobehavioral Reviews 80; 115–155. • 12. Zhou K, Dempfle A, Arcos-Burgos M, Bakker S, Banaschewski T, Biederman J et al. (2008). Meta-analysis of genome-wide linkage scans of attention deficit hyperactivity disorder. Am J Med Genet B Neuropsychiatr Genet; 147B:1392–8. • 13. Demontis D, Walters R, Martin J, Mattheisen M, Als T, Agerbo E et al (2019). Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder. Nat. Genet. 51 (1), 63–75. • 14. Brookes K, Xu X, Chen W, Zhou K, Neale B, Lowe N 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 11,934–953. • 15. Franke B, Vasquez A, Johansson S, Hoogman M, Romanos J, Boreatti-Hummer A et al. (2010). Multicenter analysis of the SLC6A3/DAT1 VNTR haplotype inpersistent ADHD suggests differential involvement of the gene in childhood and persistent ADHD. Neuropsychopharmacology 35, 656–664. • 16. Da Silva M, Cordeiro Q, Louza M, Vallada H (2009). Association between a SLC6A3 intron 8 VNTR functional polymorphism and ADHD in a Brazilian sample of adult patients. Rev Bras Psiquiatr. 2009; 31(4):387-95. • 17. Szobot C, Roman T, Hutz H, Genro J, Shih M, Hoexter M et al (2011). Molecular imaging genetics of methylphenidate response in ADHD and substance use comorbidity. Synapse 65, 154–159. • 18. de la Peña J, de la Peña I, Custodio R, Botanas C, Kim H et al (2018). Exploring the validity of proposed transgenic animal models of attentiondeficit hyperactivity disorder (ADHD). Mol. Neurobiol. https://doi. org/10.1007/s12035-017-0608. • 19. Jaber M, Dumartin B, Sagné C, Haycock J, Roubert C, Giros B et al (1999). Differential regulation of tyrosine hydroxylase in the basal ganglia of mice lacking the dopamine transporter. Eur J Neurosci 11:3499–3511. • 20. Leo D, Gainetdinov R (2013). Transgenic mouse models for ADHD. Cell Tissue Res (354:259–271). • 21. Rothhammer P, Paz Lagos L, Espinosa-Parrilla Y, Aboitiz F, Rothhammer F (2012). Variación de alelos del gen receptor de dopamina DRD4 en escolares chilenos de diferente origen étnico y su relación con riesgo de déficit atencional/hiperactividad. Rev Med Chile; 140: 1276-1281. • 22. Nikolaidis A, Gray J (2010). ADHD and the DRD4 exon III 7-repeatpolymorphism: an international meta-analysis. Soc. Cogn. Affect. Neurosci. 5,188–193. • 23. Schweren L, de Zeeuw P. Durston S (2010). MR imaging of the effects ofmethylphenidate on brain structure and function inattention-deficit/hyperactivity disorder. Eur. Neuropsychopharmacol. 23,1151–1164. • 24. Rubinstein M, Phillips J, Bunzow R, Falzone L, Dziewczapolski G, Zhang G et al. (1997). Mice lacking dopamine D4 receptors are supersensitive to ethanol, cocaine, and methamphetamine. Cell 90:991–1001. • 25. Chen J, Lipska B, Halim N, Matsumoto M, Melhem S, KolachanaB et al. (2004). Functional analysis of genetic variation incatechol-O-methyltransferase (COMT): effects on mRNA, protein, and enzymeactivity in postmortem human brain. Am. J. Hum. Genet. 75, 807–821. • 26. Corral-Frias N, Pizzagalli D, Carre J, Michalski L., Nikolova Y, Perli R et al (2016). COMT val met genotype is associated with reward learning: a replication study and meta-analysis. Genes Brain Behav. 15 (5), 503–513. • 27. Zhao L, Lin Y, Lao G, Wang Y, Guan L., Wei J (2015). Association study of dopamine receptorgenes polymorphism with cognitive functions in bipolar I disorder patients. J.Affect. Disord. 170, 85–90. • 28. Hawi Z, Cummins T, Tong J, Johnson B, Lau R, Samarrai W et al (2002). The molecular genetic architecture of attention deficit hyperactivity disorder. Mol. Psychiatry 20 (3), 289–297. • 29. Arcos-Burgos M, Jain M, Acosta M, Shively S, Stanescu H, Wallis D et al. (2010). A common variant of the latrophilin 3 gene, LPHN3, confers susceptibility to ADHD and predicts effectiveness of stimulant medication. Mol. Psychiatry 15, 1053–1066. • 30. Liu L, Guan L, Chen Y, Ji N, Li H, Li Z et al. (2011). Association analyses of MAOA in Chinese Han subjects with attention-deficit/hyperactivity disorder: family-based association test, case-control study, and quantitative traits of impulsivity. Am.J. Med. Genet. B Neuropsychiatr. Genet. 156B, 737–748. • 31. Reif A, Jacob C, Rujescu D, Herterich S, Lang S, Gutknecht L et al. (2009). Influence offunctional variant of neuronal nitric oxide synthase on impulsive behaviors inhumans. Arch. Gen. Psychiatry 66, 41–50. • 32. Gizer I, Ficks C, Waldma, I (2009). Candidate gene studies of ADHD: ameta-analytic review. Hum. Genet. 126, 51–90. • 33. Gainetdinov R, Wetsel C, Jones S, Levin D, Jaber M, Caron M (1999). Role of serotonin in EDITORIAL SCIENS // 29

José Alberto Angemi the paradoxical calming effect of psychostimulants on hyperactivity. Science 283:397–401. • 34.- Walitza S, Renner T, Dempfle A, Konrad K, Wewetzer C, Halbach A et al. (2005). Transmission disequilibrium of polymorphic variants in the tryptophan hydroxylase-2 gene in attention-deficit/hyperactivity disorder. Mol. Psychiatry 10, 1126–1132. • 35. Sheehan K, Lowe N, Kirley A, Mullins C, Fitzgerald M, Gill M, Hawi Z (2005). Tryptophan hydroxylase 2 (TPH2) gene variants associated with ADHD. Mol Psychiatry;10(10):944-9. • 36. Kebir O,Tabbane K, Sengupta S, Joober R (2008). Candidate genes and neuropsychological phenotypes in children with ADHD: review of association studies. J Psychiatry Neurosci; 34(2):88-101. • 37. Comings D, Gonzalez N, Cheng Li S (2003). A “line item” approach to the identification of genes involved in polygenic behavioral disorders: the adrenergic alpha2A (ADRA2A) gene. Am J Med Genet B Neuropsychiatr Genet; 118B:110-4. • 38. Kernie S, Liebl D, Parada L (2000). BDNF regulates eating behavior and locomotor activity in mice. EMBO J. 19, 1290–1300. • 39. Lugowska A, Mierzewska H, Bekiesinska-Figatowska M, Szczepanik E, Goszczanska-Ciuchta A, Bednarska-Makaruk M (2014). A homozygote for the c.459+1G>A mutation in the ARSA gene presents with cerebellar ataxia as the only first clinical sign of metachromatic leukodystrophy. J. Neurol. Sci. 338, 214–217. • 40. Gómez-Sintes R, Kvajo M, Gogos J, Lucas J (2014). Mice with a naturally occurring DISC1 mutation display a broad spectrum of behaviors associated to psychiatric disorders. Front. Behav. Neurosci. 8, 253. • 41. Lu T, Ogdie N, Jarvelin R, Moilanen I, Loo S, McCracken J et al.(2008). Association of the cannabinoid receptor gene (CNR1) with ADHD and post-traumatic stress disorder. Am J Med Genet B Neuropsychiatr Genet 147B:1488–1494. • 42. Bonvicini C, Faraone SV, Scassellati C(2016). Attention-deficit hyperactivity disorder in adults: a systematic review and metaanalysis of genetic, pharmacogenetic and biochemical studies. Mol Psychiatry; 21:1643. • 43. Enard W, Gehre S, Hammerschmidt K, Holter S, Blass T,Somel M et al.(2009). A humanized version of Foxp2 affects corticobasal ganglia circuits in mice. Cell;137:961–71. • 44.García-Martínez I, Sánchez-Mora C, Soler Artigas M, Rovira, P, Pagerols M, Corrales M (2017). Gene-wide association study reveals RNF122 ubiquitin ligase as a novel susceptibility gene for attention deficit hyperactivity disorder. Sci. Rep. 7 (1), 1–13. • 45. Comings D, Comings G,Muhleman D, Dietz G, Shahbahrami B, Tast D(1991). The dopamine D2 receptor locus as a modifying gene in neuropsychiatric disorders. Journal of the American Medical Association;266(13):1793–1800. • 46. Marín-Méndez J, Patiño-García, A. Segura V, Ortuño F, Gálvez M, Soutullo C (2012). Differential expression of prostaglandin D2 synthase (PTGDS) in patients with attention deficit-hyperactivity disorder and bipolar disorder. J. Affect. Disord. 138 (3), 479–484. • 47. Mortimer N, Sanchez-Mora C, Rovira P, Vilar-Ribó L, Richarte V, Corrales M et al. (2020). Transcriptome profiling in adult attention-deficit hyperactivity disorder. European Neuropsychopharmacology (2020) 41, 160–166. • 48- Rovira P, Demontis D, Sánchez-Mora C, Zayats T, Klein M, Mota N et al. (2020). Shared genetic background between children and adults with attention deficit/hyperactivity disorder. Neuropsychopharmacology, 45:1617–1626 • 49. Weiß A, Meijer M, Budeus B, Pauper M,Hakobjan M, Groothuismink J, et al. (2021). DNA methylation associated with persistent ADHD suggests TARBP1 as novel candidate. Neuropharmacology 184 (2021) 108370. • 50. Demontis D, Walters G, Athanasiadis G, Walters R, Therrien K, Nielsen T et al. (2023). Genome-wide analyses of ADHD identify 27 risk loci, refine the genetic architecture and implicate several cognitive domains. Nat Genet, 55:198–208. • 51. Cabana-Domínguez J, Llonga N, Arribas L, Alemany S, Vilar-Ribó L, Demontis D et al. (2023). Transcriptomic risk scores for attention deficit/hyperactivity disorder. Mol Psych ,28:3493–3502. • 52. Neale B, Lasky-Su J, Anney R, Franke B, Zhou K, Maller Jet al. (2008). Genome-wide association scan of attention deficit hyperactivity disorder. Am Journal of Medical Genetics Part B-Neuropsychiatric Genetics147B(8):1337-1344. • 53. Elia J, Glessner J, Wang K, Takahashi N, Shtir C., Hadley et al.(2012). Genome-wide copy number variation study associates metabotropic glutamate receptor gene networks with attention déficit hyperactivity disorder. Nat. Genet. 44, 78–84. • 54. Lesch K, Timmesfeld N, Renner J, Halperin R, Roser C, Nguyen T et al. (2008). Moleculargenetics of adult ADHD: converging evidence from genome-wide association and extended pedigree linkage studies. J Neural Transm 115:1573– 1585. • 55. Cross-Disorder Group of The Psychiatric Genomics Consortium, 2013.Identification of risk loci with shared effects on five major psychiatricdisorders: a genome-wide analysis. Lancet 381, 1371–1379. • 56. Yang L, Neale B, Liu L, Lee S, Wray N, Ji N, et al. (2013). Psychiatric GWAS Consortium: ADHD Subgroup. Polygenic Transmission and Complex Neuro Developmental Network for Attention Deficit Hyperactivity Disorder: Genome-Wide Association Study of Both Common and Rare Variants. Am J Med Genet Part B 162B:419–430. • 57. Lasky-Su J, Anney J, Neale M, Franke B, Zhou K, Maller B et al. (2008). Genome-wide association scan of the time to onset of attention deficit hyperactivity disorder. Am J Med Genet B Neuropsychiatr Genet 147B:1355–1358. • 58. Klein M, Walters R, Demontis D, Stein J, Hibar D et al. (2019). Genetic Markers of ADHD-Related Variations in Intracranial Volume Am J Psychiatry; 176(3): 228–238. • 59. Pujol-Gualdo N, Sánchez-Mora C, Ramos-Quiroga J, Ribasés M, Soler Artigas M(2021). Integrating genomics and transcriptomics: Towards deciphering ADHD. European Neuropsychopharmacology 44 ,1–13. • 60. Liu L, Feng X, Li H, Li S, Qian Q, Wang Y (2021). Deep learning model reveals potential risk genes for ADHD, especially Ephrin receptor gene EPHA5. Briefings in Bioinformatics, 22(6), 2021, 1–11. • 61. Dark C, Williams C, Bellgrove M, Hawi Z,Bryson-Richardson R(2020). Functional validation of CHMP7 as an ADHD risk gene. Translational Psychiatry 10:385.https://doi. org/10.1038/s41398-020-01077-w • 62. Hongyao H, Chun J, Xiaoyan G, Fangfang L, Jing Z, Lin Z et al. (2023). Associative gene networks reveal novel candidates important for ADHD and dislexia comorbidity. BMC Medical Genomics 16:208 https://doi. org/10.1186/s12920-023-01502-1. • 63. Ajnakina O, Shamsutdinova D, Wimberley T, Dalsgaard S, Steptoe A(2022). High polygenic predisposition for ADHD and a greater risk of all-cause mortality: a large population-based longitudinal study. Medicine (2022) 20:62 https://doi.org/10.1186/ s12916-022-02279-3. • 64.Zhou A, Cao X, Vaidhyanathan Mahaganapathy V, Azaro M, Gwin C, Wilson S et al. (2023). Common genetic risk factors in ASD and ADHD co-occurring families. Hum Genet; 142(2): 217–230. • 65. Boyle E, Li Y, Pritchard J (2017). An expanded view of complex traits: from polygenic to omnigenic. Cell. 2017; 169:1177–86. 30 // EDITORIAL SCIENS

Biblioteca