Hostname: page-component-586b7cd67f-dlnhk Total loading time: 0 Render date: 2024-11-24T17:47:14.569Z Has data issue: false hasContentIssue false
  • English
  • Français

Role of DRD2 and ALDH2 genes in bipolar II disorder with and without comorbid anxiety disorder

Published online by Cambridge University Press:  15 April 2020

Y.-S. Wang ,
S.-Y. Lee ,
S.-L. Chen ,
Y.-H. Chang ,
T.-Y. Wang ,
S.-H. Lin ,
C.-L. Wang ,
S.-Y. Huang ,
I.H. Lee  and
P.S. Chen
...Show all authors
Y.-S. Wang
Affiliation:
Institute of Behavioral Medicine, National Cheng Kung University Hospital, Tainan, Taiwan
S.-Y. Lee
Affiliation:
Department of Psychiatry, National Cheng Kung University & Hospital, Tainan, Taiwan Addiction Research Center, National Cheng Kung University, Tainan, Taiwan
S.-L. Chen
Affiliation:
Department of Psychiatry, National Cheng Kung University & Hospital, Tainan, Taiwan
Y.-H. Chang
Affiliation:
Institute of Allied Health Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan
T.-Y. Wang
Affiliation:
Department of Psychiatry, National Cheng Kung University & Hospital, Tainan, Taiwan Department of Psychiatry, Tainan Hospital, Department of Health, Executive Yuan, Tainan, Taiwan
S.-H. Lin
Affiliation:
Department of Psychiatry, National Cheng Kung University & Hospital, Tainan, Taiwan
C.-L. Wang
Affiliation:
Department of Psychiatry, National Cheng Kung University & Hospital, Tainan, Taiwan
S.-Y. Huang
Affiliation:
Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
I.H. Lee
Affiliation:
Department of Psychiatry, National Cheng Kung University & Hospital, Tainan, Taiwan
P.S. Chen
Affiliation:
Department of Psychiatry, National Cheng Kung University & Hospital, Tainan, Taiwan Addiction Research Center, National Cheng Kung University, Tainan, Taiwan
Y.K. Yang
Affiliation:
Institute of Behavioral Medicine, National Cheng Kung University Hospital, Tainan, Taiwan Department of Psychiatry, National Cheng Kung University & Hospital, Tainan, Taiwan Addiction Research Center, National Cheng Kung University, Tainan, Taiwan
R.-B. Lu*
Affiliation:
Institute of Behavioral Medicine, National Cheng Kung University Hospital, Tainan, Taiwan Department of Psychiatry, National Cheng Kung University & Hospital, Tainan, Taiwan Institute of Allied Health Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan Addiction Research Center, National Cheng Kung University, Tainan, Taiwan
*
*Corresponding author. Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, No. 138, Sheng-Li Road, Tainan 70428, Taiwan. Tel.: +886 6 235 3535x5108; fax: +886 6 302 8012. E-mail address: [email protected] (R.-B. Lu).
Get access

Abstract

The presence of comorbid anxiety disorders (AD) and bipolar II disorders (BP-II) compounds disability complicates treatment, worsens prognosis, and has been understudied. The genes involved in metabolizing dopamine and encoding dopamine receptors, such as aldehyde dehydrogenase 2 (ALDH2) and dopamine D2 receptor (DRD2) genes, may be important to the pathogenesis of BP-II comorbid with AD. We aimed to clarify ALDH2 and DRD2 genes for predisposition to BP-II comorbid with and without AD. The sample consisted of 335 subjects BP-II without AD, 127 subjects BP-II with AD and 348 healthy subjects as normal control. The genotypes of the ALDH2 and DRD2 Taq-IA polymorphisms were determined using polymerase chain reactions plus restriction fragment length polymorphism analysis. Logistic regression analysis showed a statistically significant association between DRD2 Taq-I A1/A2 genotype and BP-II with AD (OR = 2.231, P = 0.021). Moreover, a significant interaction of the DRD2 Taq-I A1/A1 and the ALDH2*1*1 genotypes in BP-II without AD was revealed (OR = 5.623, P = 0.001) compared with normal control. Our findings support the hypothesis that a unique genetic distinction between BP-II with and without AD, and suggest a novel association between DRD2 Taq-I A1/A2 genotype and BP-II with AD. Our study also provides further evidence that the ALDH2 and DRD2 genes interact in BP-II, particularly BP-II without AD.

Keywords

Bipolar II disorderAnxiety disordersDRD2ALDH2
Type
Original article
Information
European Psychiatry , Volume 29 , Issue 3 , March 2014 , pp. 142 - 148
Copyright
Copyright © European Psychiatric Association 2014

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Agarwal, DP, Goedde, HWPharmacogenetics of alcohol metabolism and alcoholism. Pharmacogenetics 1992;2:48–62.CrossRefGoogle ScholarPubMed
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorder-TR, 5th ed, Washington: American Psychiatric Association; 2000.Google Scholar
Angst, JPanic disorder: history and epidemiology. Eur Psychiatry 1998;13(Suppl. 2):51s–55s.CrossRefGoogle ScholarPubMed
Angst, JThe bipolar spectrum. Br J Psychiatry 2007;190:189–191.CrossRefGoogle ScholarPubMed
Boylan, KR, Bieling, PJ, Marriott, M, Begin, H, Young, LT, MacQueen, GMImpact of comorbid anxiety disorders on outcome in a cohort of patients with bipolar disorder. J Clin Psychiatry 2004;65:1106–1113.CrossRefGoogle Scholar
Carlson, CS, Eberle, MA, Kruglyak, L, Nickerson, DAMapping complex disease loci in whole-genome association studies. Nature 2004;429:446–452.CrossRefGoogle ScholarPubMed
Chang, YH, Chen, SL, Chen, SHet al.Low anxiety disorder comorbidity rate in bipolar disorders in Han Chinese in Taiwan. Progr Neuropsychopharmacol Biol Psychiatry 2012;36:194–197.CrossRefGoogle Scholar
Chen, CC, Lu, RB, Chen, YCet al.Interaction between the functional polymorphisms of the alcohol-metabolism genes in protection against alcoholism. Am J Hum Genet 1999;65:795–807.CrossRefGoogle ScholarPubMed
Comings, DEMolecular heterosis as the explanation for the controversy about the effect of the DRD2 gene on dopamine D2 receptor density. Mol Psychiatry 1999;4:213–215.CrossRefGoogle ScholarPubMed
Coryell, W, Endicott, J, Maser, JD, Keller, MB, Leon, AC, Akiskal, HSLong-term stability of polarity distinctions in the affective disorders. Am J Psychiatry 1995;152:385–390.Google ScholarPubMed
Crabb, DW, Edenberg, HJ, Bosron, WF, Li, TKGenotypes for aldehyde dehydrogenase deficiency and alcohol sensitivity. The inactive ALDH2(2) allele is dominant. J Clin Invest 1989;83:314–316.CrossRefGoogle ScholarPubMed
Craddock, N, Sklar, PGenetics of bipolar disorder: successful start to a long journey. Trends Genet 2009;25:99–105.CrossRefGoogle ScholarPubMed
Dandre, F, Cassaigne, A, Iron, AThe frequency of the mitochondrial aldehyde dehydrogenase I2 (atypical) allele in Caucasian, Oriental and African black populations determined by the restriction profile of PCR-amplified DNA. Mol Cell Probes 1995;9:189–193.CrossRefGoogle ScholarPubMed
Doughty, CJ, Wells, JE, Joyce, PR, Olds, RJ, Walsh, AEBipolar-panic disorder comorbidity within bipolar disorder families: a study of siblings. Bipolar Disord 2004;6:245–252.CrossRefGoogle ScholarPubMed
Endicott, J, Spitzer, RLA diagnostic interview: the schedule for affective disorders and schizophrenia. Arch Gen Psychiatry 1978;35:837–844.CrossRefGoogle Scholar
Freeman, MP, Freeman, SA, McElroy, SLThe comorbidity of bipolar and anxiety disorders: prevalence, psychobiology, and treatment issues. J Affect Disord 2002;68:1–23.CrossRefGoogle ScholarPubMed
Gerner, RH, Post, RM, Bunney, W.E. Jr.A dopaminergic mechanism in mania. Am J Psychiatry 1976;133:1177–1180.Google ScholarPubMed
Grandy, DK, Zhang, Y, Civelli, OPcr detection of the Taqa Rflp at the Drd2 locus. Hum Mol Genet 1993;2:2197.CrossRefGoogle ScholarPubMed
Hayden, EP, Klein, DN, Dougherty, LRet al.The dopamine D2 receptor gene and depressive and anxious symptoms in childhood: associations and evidence for gene-environment correlation and gene-environment interaction. Psychiatr Genet 2010;20:304–310.CrossRefGoogle ScholarPubMed
Huang, SY, Lin, WW, Ko, HCet al.Possible interaction of alcohol dehydrogenase and aldehyde dehydrogenase genes with the dopamine D2 receptor gene in anxiety-depressive alcohol dependence. Alcohol Clin Exp Res 2004;28:374–384.CrossRefGoogle ScholarPubMed
Jonsson, EG, Nothen, MM, Grunhage, Fet al.Polymorphisms in the dopamine D2 receptor gene and their relationships to striatal dopamine receptor density of healthy volunteers. Mol Psychiatry 1999;4:290–296.CrossRefGoogle ScholarPubMed
Joshi, G, Wilens, TComorbidity in pediatric bipolar disorder. Child Adolesc Psychiatr Clin N Am 2009;18:291–319.CrossRefGoogle ScholarPubMed
Judd, LL, Akiskal, HS, Schettler, PJet al.The comparative clinical phenotype and long term longitudinal episode course of bipolar I and II: a clinical spectrum or distinct disorders. J Affect Disord 2003;73:19–32.CrossRefGoogle ScholarPubMed
Keck, P.E. Jr.McElroy, SL, Arnold, LMBipolar disorder. Med Clin North Am 2001;85:645–661.CrossRefGoogle ScholarPubMed
Kelsoe, JRArguments for the genetic basis of the bipolar spectrum. J Affect Disord 2003;73:183–197.CrossRefGoogle ScholarPubMed
Keung, WM, Vallee, BLDaidzin: a potent, selective inhibitor of human mitochondrial aldehyde dehydrogenase. Proc Natl Acad Sci U S A 1993;90:1247–1251.CrossRefGoogle ScholarPubMed
Keung, WM, Vallee, BLDaidzin and its antidipsotropic analogs inhibit serotonin and dopamine metabolism in isolated mitochondria. Proc Natl Acad Sci U S A 1998;95:2198–2203.CrossRefGoogle ScholarPubMed
Kirov, G, Jones, I, McCandless, F, Craddock, N, Owen, MJFamily-based association studies of bipolar disorder with candidate genes involved in dopamine neurotransmission: DBH, DAT1, COMT, DRD2, DRD3 and DRD5. Mol Psychiatry 1999;4:558–565.CrossRefGoogle ScholarPubMed
Klein, DN, Riso, LPPsychiatric disorders problems of boundaries and comorbidity. In: Costello, CG, editors. Basic issues in psychopathology. New York: Guilford Press; 1993. p. 19–66.Google Scholar
Lamensdorf, I, Eisenhofer, G, Harvey-White, J, Nechustan, A, Kirk, K, Kopin, IJ3,4-Dihydroxyphenylacetaldehyde potentiates the toxic effects of metabolic stress in PC12 cells. Brain Res 2000;868:191–201.CrossRefGoogle ScholarPubMed
Lee, HC, Lee, HS, Jung, SHet al.Association between polymorphisms of ethanol-metabolizing enzymes and susceptibility to alcoholic cirrhosis in a Korean male population. J Korean Med Sci 2001;16:745–750.CrossRefGoogle Scholar
Lee, SY, Chen, SL, Chang, YHet al.The ALDH2 and DRD2/ANKK1 genes interacted in bipolar II but not bipolar I disorder. Pharmacogenet Genomics 2010;20:500–506.CrossRefGoogle Scholar
Leszczynska-Rodziewicz, A, Hauser, J, Dmitrzak-Weglarz, Met al.Lack of association between polymorphisms of dopamine receptors, type D2, and bipolar affective illness in a Polish population. Med Sci Monit 2005;11:289–295.Google Scholar
Li, T, Liu, XH, Sham, PCet al.Association analysis between dopamine receptor genes and bipolar affective disorder. Psychiatry Res 1999;86:193–201.CrossRefGoogle ScholarPubMed
Mann, JJ, Kapur, SA dopaminergic hypothesis of major depression. Clin Neuropharmacol 1995;18:S57–S65.CrossRefGoogle Scholar
McGuffin, P, Rijsdijk, F, Andrew, M, Sham, P, Katz, R, Cardno, AThe heritability of bipolar affective disorder and the genetic relationship to unipolar depression. Arch Gen Psychiatry 2003;60:497–502.CrossRefGoogle ScholarPubMed
McIntyre, RS, Soczynska, JK, Bottas, A, Bordbar, K, Konarski, JZ, Kennedy, SHAnxiety disorders and bipolar disorder: a review. Bipolar Disord 2006;8:665–676.CrossRefGoogle ScholarPubMed
Nakamura, K, Iwahashi, K, Matsuo, Y, Miyatake, R, Ichikawa, Y, Suwaki, HCharacteristics of Japanese alcoholics with the atypical aldehyde dehydrogenase 2*2. I. A comparison of the genotypes of ALDH2, ADH2, ADH3, and cytochrome P-4502E1 between alcoholics and nonalcoholics. Alcohol Clin Exp Res 1996;20:52–55.CrossRefGoogle ScholarPubMed
Nierenberg, AA, Dougherty, D, Rosenbaum, JFDopaminergic agents and stimulants as antidepressant augmentation strategies. J Clin Psychiatry 1998;59(Suppl. 5):60–63.Google ScholarPubMed
Noble, EP, Gottschalk, LA, Fallon, JH, Ritchie, TL, Wu, JCD2 dopamine receptor polymorphism and brain regional glucose metabolism. Am J Med Genet 1997;74:162–166.3.0.CO;2-W>CrossRefGoogle ScholarPubMed
Nothen, MM, Erdmann, J, Korner, Jet al.Lack of association between dopamine D1 and D2 receptor genes and bipolar affective disorder. Am J Psychiatry 1992;149:199–201.Google ScholarPubMed
Pallanti, S, Quercioli, L, Pazzagli, Aet al.Awareness of illness and subjective experience of cognitive complaints in patients with bipolar I and bipolar II disorder. Am J Psychiatry 1999;156:1094–1096.Google ScholarPubMed
Pearlson, GD, Wong, DF, Tune, LEet al.In vivo D2 dopamine receptor density in psychotic and nonpsychotic patients with bipolar disorder. Arch Gen Psychiatry 1995;52:471–477.CrossRefGoogle ScholarPubMed
Rakofsky, JJ, Ressler, KJ, Dunlop, BWBDNF function as a potential mediator of bipolar disorder and post-traumatic stress disorder comorbidity. Mol Psychiatry 2012;17:22–35.CrossRefGoogle ScholarPubMed
Rooke, N, Li, DJ, Li, J, Keung, WMThe mitochondrial monoamine oxidase-aldehyde dehydrogenase pathway: a potential site of action of daidzin. J Med Chem 2000;43:4169–4179.CrossRefGoogle ScholarPubMed
Rotondo, A, Mazzanti, C, Dell’Osso, Let al.Catechol o-methyltransferase, serotonin transporter, and tryptophan hydroxylase gene polymorphisms in bipolar disorder patients with and without comorbid panic disorder. Am J Psychiatry 2002;159:23–29.CrossRefGoogle ScholarPubMed
Simon, NM, Otto, MW, Wisniewski, SRet al.Anxiety disorder comorbidity in bipolar disorder patients: data from the first 500 participants in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Am J Psychiatry 2004;161:2222–2229.CrossRefGoogle Scholar
Sipila, T, Kananen, L, Greco, Det al.An association analysis of circadian genes in anxiety disorders. Biol Psychiatry 2010;67:1163–1170.CrossRefGoogle ScholarPubMed
Smith, EN, Bloss, CS, Badner, JAet al.Genome-wide association study of bipolar disorder in European American and African American individuals. Mol Psychiatry 2009;14:755–763.CrossRefGoogle ScholarPubMed
Sokoloff, P, Giros, B, Martres, MP, Bouthenet, ML, Schwartz, JCMolecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics. Nature 1990;347:146–151.CrossRefGoogle ScholarPubMed
Souery, D, Lipp, O, Mahieu, Bet al.Association study of bipolar disorder with candidate genes involved in catecholamine neurotransmission: DRD2, DRD3, DAT1, and TH genes. Am J Med Genet 1996;67:551–555.3.0.CO;2-K>CrossRefGoogle ScholarPubMed
Spitzer, RL, Endicott, J, Williams, JBResearch diagnostic criteria. Arch Gen Psychiatry 1979;36:1381–1383.CrossRefGoogle ScholarPubMed
Tamam, L[Comorbid anxiety disorders in bipolar disorder patients: a review]. Turk Psikiyatri Derg 2007;18:59–71.Google Scholar
Taylor, AE, Saint-Cyr, JADepression in Parkinson's disease: reconciling physiological and psychological perspectives. J Neuropsychiatry Clin Neurosci 1990;2:92–98.Google ScholarPubMed
Vieta, E, Suppes, TBipolar II disorder: arguments for and against a distinct diagnostic entity. Bipolar Disord 2008;10:163–178.CrossRefGoogle ScholarPubMed
Vieta, E, Gasto, C, Otero, A, Nieto, E, Vallejo, JDifferential features between bipolar I and bipolar II disorder. Compr Psychiatry 1997;38:98–101.CrossRefGoogle ScholarPubMed
Wozniak, J, Biederman, J, Monuteaux, M, Richards, J, Faraone, SVParsing the comorbidity between bipolar disorder and anxiety disorders: a familial risk analysis. J Child Adolesc Psychopharmacol 2002;12:101–111.CrossRefGoogle ScholarPubMed
Zutshi, A, Reddy, YC, Thennarasu, K, Chandrashekhar, CRComorbidity of anxiety disorders in patients with remitted bipolar disorder. Eur Arch Psychiatry Clin Neurosci 2006;256:428–436.CrossRefGoogle ScholarPubMed
Submit a response

Comments

No Comments have been published for this article.