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The DRD2 gene and the risk for alcohol dependence in bipolar patients

Published online by Cambridge University Press:  16 April 2020

P. Gorwood ,
F. Bellivier ,
J. Adès  and
M. Leboyer
P. Gorwood*
Affiliation:
Hospital Louis Mourier (Service de Psychiatrie adulte du Professeur Adès)., Colombes, 92700, France CNRS UMR 7593 (Laboratoire ‘Personnalité et conduites adaptatives’ du Professeur Jouvent), Paris, France
F. Bellivier
Affiliation:
Hôpital Albert Chenevier et Henri Mondor, AP-HP (Service de psychiatrie adulte du Professeur Rouillon), Créteil, 94000, France INSERM U 513 (Laboratoire neurobiologie et Psychiatrie), Créteil, 94000, France
J. Adès
Affiliation:
Hospital Louis Mourier (Service de Psychiatrie adulte du Professeur Adès)., Colombes, 92700, France CNRS UMR 7593 (Laboratoire ‘Personnalité et conduites adaptatives’ du Professeur Jouvent), Paris, France
M. Leboyer
Affiliation:
Hôpital Albert Chenevier et Henri Mondor, AP-HP (Service de psychiatrie adulte du Professeur Rouillon), Créteil, 94000, France INSERM U 513 (Laboratoire neurobiologie et Psychiatrie), Créteil, 94000, France
*
*Correspondence and reprints: Philip Gorwood, M.D., Ph.D., Service de Psychiatrie, Hôpital Louis Mourier 178, rue des Renouillers, 92701 Colombes cedex, France
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Summary

The high co-morbidity between bipolar disorder and alcohol dependence may have different explanations, one of them being the existence of common genetic factors for the two disorders. Several candidate genes may be involved but the genes acting in the dopaminergic pathway may be more specifically involved. We have thus tested the role of the gene encoding the D2 dopamine receptor (TaqI A1 allele) in the potentially shared vulnerability to alcohol dependence and bipolar disorder.

One hundred and twenty-two French (for at least two generations) patients were recruited on the basis of hospital or outpatient files and were interviewed with the DIGS. The A1 allele frequencies were compared between four groups, namely, with bipolar patients and co-morbid alcohol dependence (N = 21), with bipolar patients without alcohol morbidity (N = 31), with alcohol dependence without mood disorder (N = 35) and unaffected controls (N = 35).

The Hardy Weinberg equilibrium for the DRD2 Taq1 A1 genotypes was respected for the sample as a whole, and for each subsample. We observed that 42.9% of control subjects have at least one A1 allele, a frequency which is not significantly different from the one observed in the affected sample as a whole (39.1%), neither from patients with alcohol dependence (37.1%), patients with bipolar disorder (48.4%) nor patients with alcohol dependence and bipolar disorder (28.6%). The regression analysis based on the three variables (bipolar disorder, alcohol dependence and interaction between these two disorders) does not explain the presence of the A1 allele of the DRD2 gene.

We thus found no evidence for a significant role of the A1 allele of the D2 dopamine receptor gene in the specific association between bipolar disorder and alcohol dependence in our sample.

Keywords

alcoholismco-morbiditygeneticsmood disorder
Type
Original Article
Information
European Psychiatry , Volume 15 , Issue 2 , March 2000 , pp. 103 - 108
Copyright
Copyright © Éditions scientifiques et médicales Elsevier SAS 2000

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References

Adès, JLes relations entre alcoolisme et pathologie mentale.Congrès de Psychiatrie et de Neurologie de Langue Française. LXXXVI° Session, Tome III 1989 itions MassonGoogle Scholar
Amadeo, SAbbar, MFourcade, M.LWacksman, GLeroux, MMadec, A et al. D2 Dopamine receptor gene and alcoholism. J Psychiat Res 2 1993 173–179CrossRefGoogle Scholar
Blum, KNoble, E.PSheridan, P.JMontgomery, ARitchie, TJagadeeswaran, P et al. Allelic association of human dopamine D2 receptor gene and alcoholism. JAMA 263 1990 2055–2060CrossRefGoogle ScholarPubMed
Blum, KNoble, E.PSheridan, P.JFinley, OMontgomery, ARitchie, T et al. Association of the A1 allele of the D2 dopamine receptor gene with severe alcoholism. Alcohol 8 1991 409–416CrossRefGoogle ScholarPubMed
Blum, KNoble, ESheridan, PMontgomey, ARitchie, TOzkaragoz, T et al. Genetic predisposition in alcoholism: association of the D2 dopamine recepetor Taq1 B1 RFLP with severe alcoholics. Alcohol 10 1993 59–67CrossRefGoogle Scholar
Cadoret, RFamilial transmission of psychiatric disorders associated with alcoholism.Begleiter, HKissin, BThe genetics of alcoholism. 1995 Oxford: Oxford University Press 40–69Google Scholar
Chiodo, LAntelman, STricyclic antidepressants induce subsensitivity of presynaptic dopamine autoreceptors. Eur J Pharmacol 64 1980 203–204CrossRefGoogle ScholarPubMed
Comings, DComings, BDonn Muhleman, M.SDietz, GShahbahrami, BTast, D et al. The dopamine D2 receptor locus as a modifying gene in neuropsychiatric disorders. JAMA 266 1991 1793–1800CrossRefGoogle ScholarPubMed
Cook, CPalsson, GTurner, AHomes, DBrett, PCurtis, D et al. A genetic linkage study of the D2 dopamine receptor locus in heavy drinking and alcoholism. Br J Psychiatry 169 1996 243–248CrossRefGoogle ScholarPubMed
Craddock, NRoberts, QWilliams, NMcGuffin, POwen, M.JAssociation study of bipolar disorder using a functional polymorphism (Ser311 >Cys) in the dopamine D2 receptor gene. Psychiatr Genet 5 1995 63–65CrossRefGoogle ScholarPubMed
Curtis, DSherrington, RBrett, PHolmes, D.SKalsi, GBrynjolfsson, J et al. Genetic linkage analysis of manic depression in Iceland. J R Soc M 86 1993 506–510Google ScholarPubMed
De Bruyn, ASouery, DMendelbaum, KMendlewicz, JVanBroeckhoven, CA linkage study between bipolar disorder and genes involved in dopaminergic and GABAergic neurotransmission. Psychiatr Genet 6 1996 67–73CrossRefGoogle ScholarPubMed
DeBruyn, AMendelbaum, KSandkuijl, L.ADelvenne, VHirsch, DStaner, L et al. Nonlinkage of bipolar illness to tyrosine hydroxylase, tyrosinase, and D2 and D4 dopamine receptor genes on chromosome 11. Am J Psychiatry 151 1 1994 102–106Google Scholar
Depue, RIacono, WNeurobehavioral aspects of affective disorders. Annu Rev Psychol 40 1989 457–49210.1146/annurev.ps.40.020189.002325CrossRefGoogle ScholarPubMed
DiChiara, GImperato, ADrugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. Proc Natl Acad Sci U S A 85 1988 5274–5278CrossRefGoogle Scholar
Ewald, HMors, OFriedrich, UFlint, TKruse, TExclusion of linkage between manic depressive illness and tyrosine hydroxylase and dopamine D2 receptor genes. Psychiatr Genet 4 1994 13–22CrossRefGoogle ScholarPubMed
Gerner, RPost, RBunney, WA dopaminergic mechanism in mania. Am J Psychiatry 133 1976 1177–1180Google ScholarPubMed
Goodwin, FMurphy, DBrodie, HBunney, WL Dopa, catecholamines, and behavior: A clinical and biochemical study in depressed patients. Biol Psychiatry 2 1970 341–366Google ScholarPubMed
Gorwood, PAdès, JFeingold, JAre genes coding for dopamine receptors implicated in alcoholism? Eur Psychiatry 9 1994 63–69CrossRefGoogle Scholar
Gorwood, PBatel, PGouya, LCourtois, FFeingold, JAdès, JReappraisal of the association between the DRD2 gene, alcoholism and addiction. Eur Psychiatry this issueGoogle Scholar
Grandy, D.KZhang, YCivelli, OPCR detection of the TaqA RFLP at the DRD2 locus. Hum Mol Genet 2 1993 2197CrossRefGoogle ScholarPubMed
Holmes, DBrynjolfsson, JBrett, PCurtis, DPetursson, HSherrington, R et al. No evidence for a susceptibility locus predisposing to manic depression in the region of the dopamine (D2) receptor gene. Br J Psychiatry 158 1991 635–641CrossRefGoogle ScholarPubMed
Ingraham, L.JWender, P.HRisk for affective disorder and alcohol and other drug abuse in the relatives of affectively ill adoptees. J Affect Disord 26 1992 45–51CrossRefGoogle ScholarPubMed
Jacobs, DSilverstone, TDextroamphetamine induced arousal in human subjects as a model for mania. Psychol M 16 1986 323–32910.1017/S0033291700009132CrossRefGoogle ScholarPubMed
Kelsoe, J.RKristbjanarson, HBergesch, PShilling, PHirsch, SMirow, A et al. A genetic linkage study of bipolar disorder and 13 markers on chromosome 11 including the D2 dopamine receptor. Neuropsychopharmacology 9 1993 293–301CrossRefGoogle ScholarPubMed
Kessler, RMcGonagle, KZhao, SNelson, CHughes, MEshleman, S et al. Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United-States: results from the National Comorbidity Survey. Arch Gen Psychiatry 51 1994 8–19CrossRefGoogle ScholarPubMed
Leboyer, MMalafosse, ABoularan, SCampion, DGheysen, FSamolyk, D et al. A tyrosine hydroxylase polymorphisms reveals an association with manic-depressive illness. Lancet 335 1990 1219CrossRefGoogle Scholar
Lippa, A.SAntelman, S.MFisher, A.ECanfield, R.DNeurochemical mediation of reward: a significant role of dopamine? Pharmacol Biochem Behav 1 1973 23–28CrossRefGoogle ScholarPubMed
Loparev, V.NCartas, M.AMonken, CVelpandi, ASrinivajan, AAn efficient and simple method of DNA extraction from whole blood and cell lines to identify infectious agents. J Virol Methods 34 1991 105–112CrossRefGoogle ScholarPubMed
Maier, WLichtermann, DMinges, JDelmo, CHeun, RThe relationship between bipolar disorder and alcoholism: a controlled family study. Psychol M 25 1995 787–796CrossRefGoogle ScholarPubMed
Maier, WMerikangas, KCo-occurrence and contransmission of affective disorders and alcoholism in families. Br J Psychiatry 30 Suppl 1996 93–100CrossRefGoogle Scholar
Mitchell, PSelbie, LWaters, BDonald, JVivero, CTully, M et al. Exclusion of close linkage of bipolar disorder to dopamine D1 and D2 receptor gene markers. J Affect Disord 25 1992 1–11CrossRefGoogle ScholarPubMed
Murphy, DBrodie, HGoodwin, FBunney, WRegular induction og hypomania by L Dopa in ‘bipolar’ manic depressive patients. Nature 229 1971 135–136CrossRefGoogle Scholar
Murphy, J.MMcBride, W.JLumeng, LLi, T.KMonoamine and metabolite levels in CNS regions of the P line of alcohol preferring rats after acute and chronic ethanol treatment. Pharmacol Biochem Behav 19 1983 849–856CrossRefGoogle Scholar
Nanko, SFukuda, RHattori, MSasaki, TDai, X.YKanba, S et al. Linkage studies between affective disorder and dopamine D2, D3, and D4 receptor gene loci in four Japanese pedigrees. Psychiatry Res 52 1994 149–157CrossRefGoogle ScholarPubMed
Neiswanger, KHill, S.YKaplan, B.BAssociation and linkage studies of the TAQ1 A1 allele at the dopamine D2 receptor gene in samples of female and male alcoholics. Am J Med Gen 60 1995 267–271CrossRefGoogle Scholar
Noble, ESyndulko, KFitch, JRitchie, TBohlman, MGuth, P et al. D2 dopamine receptor Taq1 A alleles in medically ill alcoholic and nonalcoholic patients. Alcohol 29 1994 729–744Google Scholar
Nothen, M.MErdmann, JKorner, JLanczik, MFritze, JFimmers, R et al. Lack of association between dopamine D1 and D2 receptor genes and bipolar affective disorder. Am J Psychiatry 149 1992 199–201Google ScholarPubMed
Nurnberger, J.IBlehar, M.CKaufmann, C.AYork Cooler, CSimpson, S.GHarkavy Friedman, J et al. Diagnostic Interview for Genetic Studies: rational, unique features, and training. Arch of Gen Psychiatry 51 1994 849–862CrossRefGoogle Scholar
Parsian, ATodd, RDevor, EO'Malley, KSuarez, BReich, T et al. Alcoholism and alleles of the human D2 dopamine receptor locus. Arch Gen Psychiatry 48 1991 655–663CrossRefGoogle ScholarPubMed
Perez, D.ECastro, ISantos, JTorres, PVisedo, GSaiz Ruiz, JLlinares, C et al. A weak association between TH and DRD2 genes and bipolar affective disorder in a Spanish sample. J Med Genet 32 1995 131–134CrossRefGoogle Scholar
Puig Antich, JGoetz, DDavies, MKaplan, TDavies, SOstrow, L et al. A controlled family history study of prepubertal major depressive disorder. Arch Gen Psychiatry 46 1989 406–41810.1001/archpsyc.1989.01810050020005CrossRefGoogle ScholarPubMed
Regier, D.AFarmer, M.ERae, D.SLocke, B.ZKeith, S.JJudd, L.L et al. Comorbidity of mental disorders with alcohol and other drug abuse. Results from the Epidemiologic Catchment Area (ECA) Study. JAMA 264 1990 2511–2518CrossRefGoogle ScholarPubMed
Reich, LDavies, RHimmelhoch, JExcessive alcohol use in manic depressive illness. Am J Psychiatry 131 1974 83–85CrossRefGoogle ScholarPubMed
Routtenberg, AThe reward system of the brain. Sci Am 239 1978 122–131CrossRefGoogle ScholarPubMed
Schuckit, MGenetic and clinical implications of alcoholism and affective disorder. Am J Psychiatry 143 1986 140–147Google ScholarPubMed
Silverstone, TDopamine, mood and manic depressive psychosis.Garattini, SDepressive disorders. 1978 Stuttgart: FK Schattauer Verlag 419–430Google Scholar
Silverstone, TResponse to bromocriptine distinguishes bipolar from unipolar depression. Lancet 1 1984 903–904CrossRefGoogle ScholarPubMed
Smith, SO'Hara, BPersico, AGprelick, D.ANewlin, D.BVlahov, D et al. The D2 Dopamine Taq B1 RFLP appears more frequently in polysubstance abusers. Arch Gen Psychiatry 49 1992 723–727CrossRefGoogle ScholarPubMed
Stellar, J.RStellar, EThe neurobiology of motivation and reward. 1985 New York: Springer VerlagCrossRefGoogle Scholar
Todd, R.DGeller, BNeuman, RFox, L.WHickok, JIncreased prevalence of alcoholism in relatives of depressed and bipolar children. J Am Acad Child Adolesc Psychiatry 35 1996 716–724CrossRefGoogle ScholarPubMed
Tsiouris, S.JBreschel, T.SXu, JMc Innis, M.GMcMahon, F.JLinkage disequilibrium analysis of G olf alpha (GNAL) in bipolar affective disorder. Am J Med Genet 67 1996 491–4943.0.CO;2-I>CrossRefGoogle Scholar
Uhl, G.RPersico, A.MSmith, S.SCurrent excitement with dopamine receptor gene alleles in substance abuse. Arch Gen Psychiatry 49 1992 157–160CrossRefGoogle ScholarPubMed
VanPraag, HKorf, JCentral monoamine deficiency in depressions: Causative of secondary phenomenon? Pharmakopsychiatr Neuropsychophramakol 8 1975 322–326CrossRefGoogle Scholar
Waler, MB, Murphy, JM, McBride, WJ, Lumeng, L, Li, TK. Pharmacol Biochem Behav 1986; 24: 617.CrossRefGoogle Scholar
West, ALithium treatment of depressed alcoholics: A hypothesis. Am J Psychiatry 140 1983 814Google ScholarPubMed
Winokur, GCoryell, WEndicott, JKeller, MAkiskal, HSolomon, DFamilial alcoholism in manic depressive (bipolar) disease. Am J Med Genet 67 1996 197–2013.0.CO;2-E>CrossRefGoogle ScholarPubMed
Winokur, GCoryell, WAkiskal, H.SMaser, J.DKeller, M.BEndicott, J et al. Alcoholism in manic depressive (bipolar) illness: familial illness, course of illness, and the primary secondary distinction. Am J Psychiatry 152 1995 365–372Google ScholarPubMed
Wise, R.ARompre, P.PBrain dopamine and reward. Ann Rev Psychol 40 1989 191–225CrossRefGoogle ScholarPubMed
Wise, R.AAction of drugs of abuse on brain reward systems. Pharamacol Biochem Behav 13 Suppl 1980 213–23310.1016/S0091-3057(80)80033-5CrossRefGoogle ScholarPubMed
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