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El alelo A1 del gen del receptor D2 de dopamina (polimorfismos Taql A) se asocia con personalidad antisocial en una muestra de pacientes dependientes de alcohol

Published online by Cambridge University Press:  12 May 2020

G. Ponce
Affiliation:
Unidad de conductas adictivas, Servicio de Psiquiatría, Edificio de Medicina Comunitaria, Hospital Universitario 12 de Octubre, Avda. de Córdoba s/n, 28041Madrid, España
M. A. Jiménez-Arriero
Affiliation:
Unidad de conductas adictivas, Servicio de Psiquiatría, Edificio de Medicina Comunitaria, Hospital Universitario 12 de Octubre, Avda. de Córdoba s/n, 28041Madrid, España
G. Rubio
Affiliation:
Unidad de conductas adictivas, Servicio de Psiquiatría, Edificio de Medicina Comunitaria, Hospital Universitario 12 de Octubre, Avda. de Córdoba s/n, 28041Madrid, España
J. Hoenicka
Affiliation:
Departamento de Biología Molecular, Universidad Complutense, Madrid, España
I. Ampuero
Affiliation:
Departamento de Biología Molecular, Universidad Complutense, Madrid, España
J. A. Ramos
Affiliation:
Departamento de Biología Molecular, Universidad Complutense, Madrid, España
T. Palomo
Affiliation:
Unidad de conductas adictivas, Servicio de Psiquiatría, Edificio de Medicina Comunitaria, Hospital Universitario 12 de Octubre, Avda. de Córdoba s/n, 28041Madrid, España
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Resumen

Propósito:

La presencia del alelo Al del gen del receptor D2 de dopamina se ha asociado con predisposición al alcoholismo, aunque hay datos limitados sobre su expresión fenotípica en el alcoholismo.

Objetivos:

Determinar la importancia del alelo Al en las variables clínicas de la dependencia de alcohol.

Metodología:

Se estudió una muestra de 103 varones dependientes de alcohol. Se seleccionó a todos los pacientes consecutivamente del hospital general y entornos comunitarios. Los diagnósticos se hicieron con la Entrevista Clínica Estructurada para el DSM-III-R (SCID), y el Examen Internacional del Trastorno de la Personalidad (IPDE). El diagnóstico de alcoholismo familiar se hizo por entrevista directa o con los Criterios Diagnósticos para la Investigación-Historia Familiar (RDC-FH). Se utilizó el Índice de Gravedad de la Adicción (ASI) y la Escala de Gravedad de la Dependencia de Alcohol (SADS) para evaluar la gravedad de la dependencia del alcohol. La genotipación se hizo por los métodos de reacción en cadena de la polimerasa (RCP) y polimorfismos de longitud de fragmentos de restricción (PLFR).

Resultados:

El treinta y nueve por ciento aproximadamente de la muestra portaba el alelo Al (grupo A1+). Este grupo tenía prevalencias más altas de trastorno antisocial de la personalidad (60% frente a 15,9%) e historia familiar de alcoholismo (72,5% frente a 52,4%). Además, el grupo A1+ tenía un comienzo temprano del abuso de alcohol y más problemas con la bebida. La presencia de A1+ era el factor principal que explicaba el diagnóstico de trastorno antisocial de la personalidad, pero el peso de este factor no era suficiente para explicar las complicaciones evaluadas por el ASI.

Conclusiones:

Nuestros resultados apoyan la existencia de una asociación entre el alelo Al y factores derivados de la deficiencia dopaminérgica, denominada de otro modo síndrome de deficiencia de la recompensa.

Type
Artículo original
Copyright
Copyright © European Psychiatric Association 2004

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References

Bibliografía

Blum, K, Noble, EP, Sheridan, PJ, Montgomery, A, Ritchie, T, Jagadeeswaran, P, et al.Allelic association of human dopamine D2 receptor gene in alcoholism. J Am Med Assoc 1990;263:2055–60.CrossRefGoogle ScholarPubMed
Blum, K, Sheridan, PJ, Wood, RC, Braverman, ER, Chen, TJH, Comings, DE. Dopamine D2 receptor gene variante: association and linkage studies in impulsive-addictive- compulsive behaviour. Pharmacogenetics 1995;5:121–1.CrossRefGoogle Scholar
Noble, EP. D2 dopamine receptor gene in psychiatric and neurologic disorders and its phenotypes. Am J Med Genet 2003;ll6(Suppl 1):103–25.CrossRefGoogle Scholar
Cloninger, CR. D2 dopamine receptor gene is associated but not linked with alcoholism. J Am Med Assoc 1991;266:1833–4.CrossRefGoogle Scholar
Bolos, AM, Dean, M, Lucase-Derse, S, Ramsburg, M, Brown, GL, Goldman, D, et al.Population and pedigree studies reveal a lack of association between the dopamine D2 receptor gene and alcoholism. J Am Med Assoc 1990;264:3156–60.CrossRefGoogle ScholarPubMed
Gelernter, J, O’Malley, S, Risch, N, Kranzler, HR, Krystal, J, Merikangas, K, et al.No association between an alíele of the D2 dopamine receptor gene (DRD2) and alcoholism. J Am Med Assoc 1991;266:1801–7.CrossRefGoogle Scholar
Noble, EP. Addiction and its reward procese through polymorphisms of the D2 dopamine receptor gene: a review. Eur Psychiatry 2000;15:7989.CrossRefGoogle Scholar
Gelernter, J, Goldman, D, Risch, N. The Al alíele of the D2 dopamine receptor gene and alcoholism. J Am Med Assoc 1993;269:1673–7.CrossRefGoogle Scholar
Noble, EP, Syndulko, K, Fitch, J, Ritchie, T, Bohman, M, Guth, P, et al.D2 dopamine receptor Taq 1 alíeles in medically ill alcoholic and non alcoholic patients. Alcohol Alcohol 1994;29:729–44.Google Scholar
Lawford, B, Young, R, Rowell, J, Gibson, J, Feeney, G, Ritchie, T, et al.Association of the D2 dopamine receptor Al alíele with alcoholism: medical severity of alcoholism and type of Controls. Biol Psychiatry 1997;41:385–93.CrossRefGoogle Scholar
Cook, BL, Wang, ZW, Crowe, RR, Hauser, R, Freimer, M. Alcoholism and the D2 receptor gene. Alcohol Clin Exp Res 1992;16:806–9.CrossRefGoogle ScholarPubMed
Turner, E, Ewing, J, Shilling, P, Smith, TL, Irwin, M, Schuckit, M, et al.Lack of association between an RFLP near the dopamine D2 receptor gene and severe alcoholism. Biol Psychiatry 1992;31:285–90.CrossRefGoogle ScholarPubMed
Hietala, J, Pohjalainen, T, Heikkila-Kallio, U, West, C, Salaspuro, M, Syvalahti, E. Allelic association between D2 but not DI dopamine receptor gene and alcoholism in Finland. Psychiatr Genet 1997;7: 1925.CrossRefGoogle ScholarPubMed
Gorwood, P, Batel, P, Gouya, L, Courtois, F, Feingold, J, Ades, J. Reappraisal of the association between the DRD2 gene, alcoholism and addiction. Eur Psychiatry 2000;15:90–6.CrossRefGoogle ScholarPubMed
Parsian, A, Todd, RD, Devor, EJ, O’Malley, KL, Suarez, BK, Reich, T, et al.Alcoholism and alíeles of the human D2 receptor locus: studies of association and linkage. Arch Gen Psychiatry 1991;48:655–63.CrossRefGoogle Scholar
Hill, SY, Zezza, N, Wipprecht, G, Locke, J, Neiswanger, K. Personality traits and dopamine receptors (D2 and D4): linkage studies in families of alcoholics. Am J Med Genet 1999;88:634–41.3.0.CO;2-M>CrossRefGoogle Scholar
Bau, CH, Almeida, S, Hutz, MH. The TaqlAI alíele of the dopamineD2 receptor gene and alcoholism in Brazil: association and interaction with stress and harm avoidance on severity prediction. Am J Med Genet 2000;96:302–6.3.0.CO;2-I>CrossRefGoogle Scholar
Spitzer, RL, Williams, JBW. Structured clinical interview for DSM-III-R, patient versión (SCID-P). New York: Biometrics Research Department, State Psychiatry Institute; 1985.Google Scholar
Bueno, JA, Humbert, M, Sabanes, F, Salvador, L. Sistema, RDC. Criterios diagnósticos de Investigación (research diagnostic criteria). Madrid: Instituto de Medicina Psicológica de Barcelona, Editores Médicos SA; 1989.Google Scholar
World Health Organization. International personality disorder examination (IPDE)-DSM-IV-module. Geneva: WHO; 1995.Google Scholar
Schuckit, MA, Klein, J, Twitchell, G, Smith, T. Personality test scores as predictors of alcoholism almost a decade latern Am J Psychiatry 1994;151:1038–42.Google Scholar
Cadoret, RJ, Yates, WR, Troughton, E, Woodwoth, G, Stewart, MA. Genetic-environmental interaction in the genesis of aggressivity and conduct disorders. Arch Gen Psychiatry 1995;52:916–24.CrossRefGoogle ScholarPubMed
Comings, DE, Wu, H, Chin, L, et al.Polygenic inheritance of Tourette’s syndrome (stuttering, attentiondeficit hyperactivity, conduct and oppositional defiant disorder): the addictive and subtractive effects of three dopaminergic genes-DRD2, D0H and DAT. Am J Med Genet 1996;67:264–88.3.0.CO;2-N>CrossRefGoogle Scholar
McLellan, AT, Luborsky, L, Woody, GE, O’Brien, CP. An improved diagnostic evaluation instrument for substance abuse patients: the Addiction Severity Index. J Nerv Ment Dis 1980;168:2633.CrossRefGoogle ScholarPubMed
Rubio, G, Urosa, B, Santo-Domingo, J. Validación de la escala de la intensidad de la dependencia alcohólica (EIDA). Psiquiatría Biol 1998;5(Suppl l):44–7.Google Scholar
Stockwell, TR, Murphy, D, Hodgson, R. The severity of alcohol dependence questionnaire: its use, reliability and validity. Br J Addict 1983;78:145–55.CrossRefGoogle ScholarPubMed
Eriksson, M, Berggren, U, Blennow, K, Fahlke, C, Mansson, JE, Balldin, J. Alcoholics with the dopamine receptor DRD2 Al alíele have lower platelet monoamine oxidase-B activity than those with the A2 alíele: a preliminary study. Alcohol Alcohol 2000;35:493–8.CrossRefGoogle Scholar
Ratsma, JE, van der Stelt, O, Schoffelmeer, ANM, Westerveld, A, Gunning, WB. P3 event-related potential, dopamine D2 receptor A I alíele, and sensation-seeking in adult children of alcoholice. Alcohol Clin Exp Res 2001;25:960–7.CrossRefGoogle Scholar
Parsian, A, Cloninger, CR, Zhang, ZH. Functional variant in the DRD2 receptor promoter región and subtypes of alcoholism. Am J Med Genet 2000;96:407–11.3.0.CO;2-1>CrossRefGoogle ScholarPubMed
Rubio, G, León, G, Ferre, F, Pascual, J, Santo-Domingo, J. Clinical significance of Cloninger’s classification in a sample of Spanish alcoholic men. Addiction 1998;93:93101.CrossRefGoogle Scholar
Connor, JP, Young, RM, Lawford, BR, Ritchie, TL, Noble, ERD(2) dopamine receptor (DRD2) polymorphism is associated with severity of alcohol dependence. Eur Psychiatry 2002; 17:1723.CrossRefGoogle ScholarPubMed
Noble, EP, Ozkaragoz, TZ, Ritchie, T, Zhang, X, Belin, TR, Sparkes, RS. D2 and D4 dopamine receptor polymorphism and personality. Am J Med Genet 1998;81:257–67.3.0.CO;2-E>CrossRefGoogle Scholar
Noble, EP, Blum, K, Ritchie, T, Montgomery, A, Sheridan, PJ. Allelic association of the D2 dopamine receptor gene with receptor-binding characteristics in alcoholism. Arch Gen Psychiatry 1991;48:648–54.CrossRefGoogle ScholarPubMed
Pohjalainen, T, Rinne, JO, Nagren, K, Lehikoinen, P, Anttila, K, Syvalahti, EKG, et al.The Al alíele of the human D2 dopamine receptor gene predicts low D2 receptor availability in healthy volunteers. Mol Psychiatry 1998;3:256–60.CrossRefGoogle Scholar
Blum, K, Sheridan, PJ, Wood, RC, Braverman, ER, Chen, TJH, Culi, JG, et al.The D2 dopamine receptor gene as a determinan” of reward deficiency syndrome. J R Soc Med 1996;89:396400.CrossRefGoogle Scholar
Comings, DE, Blum, K. Reward deficiency syndrome: genetic aspects of behavioral disorders. Prog Brain Res 2000;126:325–41.CrossRefGoogle ScholarPubMed
Koob, GF, Bloom, FE. Cellular and molecular mechanisms of drug dependence. Science 1988;242:715–23.CrossRefGoogle ScholarPubMed
Koob, GF, Sanna, PP, Bloom, FE. Neuroscience of addiction. Neuron 1998;21:467–76.CrossRefGoogle ScholarPubMed
Di Chiara, G, Imperato, A. Drug abused by humane preferentially increase synaptic dopamine concentration in the mesolimbic system of freely moving rats. Proc Nati Acad Sci USA 1988;85:5274.CrossRefGoogle Scholar
Laine, TP, Ahonen, A, Rasanen, P, Pohjalainen, T, Tiihonen, J, Hietala, J. The Al alíele of the D2 dopamine receptor gene is associated with high dopamine transponer density in detoxified alcoholics. Alcohol Alcohol 2001;36:262–5.CrossRefGoogle Scholar