Korean Journal of Biological Psychiatry (생물정신의학)

The Korean Society of Biological Psychiatry (대한생물정신의학회)
권호 표지

Association between COMT and 5-HTTLPR Polymorphisms in Korean Patients with Panic Disorder : A Replication Study

한국 공황장애 환자에서 COMT 및 5-HTTLPR 다형성의 연관 분석 : 재현 연구

  • Kim, Se-Woong (Department of Psychiatry, CHA Bundang Medical Center, CHA University) ;
  • Choi, Tai Kiu (Department of Psychiatry, CHA Bundang Medical Center, CHA University) ;
  • Lee, Sang-Hyuk (Department of Psychiatry, CHA Bundang Medical Center, CHA University)
  • 김세웅 (차의과학대학교 분당차병원 정신건강의학교실) ;
  • 최태규 (차의과학대학교 분당차병원 정신건강의학교실) ;
  • 이상혁 (차의과학대학교 분당차병원 정신건강의학교실)
  • Received : 2016.06.21
  • Accepted : 2016.09.05
  • Published : 2016.11.30
Download PDF
⟨ Previous Next ⟩

Abstract

Objectives We investigated whether the catechol-O-methyltransferase (COMT) and serotonin related gene polymorphisms may be associated with agoraphobia in patients with panic disorder in Korea. Methods The COMT gene (rs4680), 5-hydroxytryptamine (serotonin) transporter linked polymorphic region (5-HTTLPR) gene (rs25531), serotonin receptor 1A (HTR1A) gene (rs6295) genotypes were analyzed in 406 patients with panic disorder and age-sex matched 206 healthy controls. Patients with panic disorder were dichotomized by the presence of agoraphobia. The following instruments were applied : the Beck Depression Inventory, the Beck Anxiety Inventory, the Panic Disorder Severity Scale. Results There was a significant difference in the distribution of 5-HTTLPR genotype between panic patients with agoraphobia and without agoraphobia (p = 0.024). That is, the panic patients with agoraphobia had a significant excess of the less active 5-HTTLPR allele (S allele). (p = 0.039) Also, we replicated previous western reports which indicated a significant difference in the distribution of COMT genotype between the patients with panic disorder and the healthy controls (p = 0.040). However, no significant associations of agora-phobia or panic disorder with HTR1A gene polymorphisms were found. Conclusions This result supports that the COMT polymorphisms may be associated with panic disorder and suggests that the 5-HTTLPR polymorphisms may play a role in the pathogenesis of agoraphobia in the Korean patients with panic disorder.

Keywords

References

  1. Hettema JM, Neale MC, Kendler KS. A review and meta-analysis of the genetic epidemiology of anxiety disorders. Am J Psychiatry 2001;158:1568-1578. https://doi.org/10.1176/appi.ajp.158.10.1568
  2. Kessler RC, Chiu WT, Jin R, Ruscio AM, Shear K, Walters EE. The epidemiology of panic attacks, panic disorder, and agoraphobia in the National Comorbidity Survey Replication. Arch Gen Psychiatry 2006;63:415-424. https://doi.org/10.1001/archpsyc.63.4.415
  3. Kendler KS, Karkowski LM, Prescott CA. Fears and phobias: reliability and heritability. Psychol Med 1999;29:539-553. https://doi.org/10.1017/S0033291799008429
  4. Tsuang M, Domschke K, Jerskey BA, Lyons MJ. Agoraphobic behavior and panic attack: a study of male twins. J Anxiety Disord 2004;18:799-807. https://doi.org/10.1016/j.janxdis.2003.10.001
  5. Gelernter J, Bonvicini K, Page G, Woods SW, Goddard AW, Kruger S, et al. Linkage genome scan for loci predisposing to panic disorder or agoraphobia. Am J Med Genet 2001;105:548-557. https://doi.org/10.1002/ajmg.1496
  6. Perna G, Dacco S, Menotti R, Caldirola D. Antianxiety medications for the treatment of complex agoraphobia: pharmacological interventions for a behavioral condition. Neuropsychiatr Dis Treat 2011;7:621-637.
  7. Lonsdorf TB, Ruck C, Bergstrom J, Andersson G, Ohman A, Schalling M, et al. The symptomatic profile of panic disorder is shaped by the 5-HTTLPR polymorphism. Prog Neuropsychopharmacol Biol Psychiatry 2009;33:1479-1483. https://doi.org/10.1016/j.pnpbp.2009.08.004
  8. Kang E, Choe AY, Kim B, Lee JY, Choi TK, Na HR, et al. Serotonin transporter and COMT polymorphisms as independent predictors of health-related quality of life in patients with panic disorder. J Korean Med Sci 2016;31:757-763. https://doi.org/10.3346/jkms.2016.31.5.757
  9. Knuts I, Esquivel G, Kenis G, Overbeek T, Leibold N, Goossens L, et al. Therapygenetics: 5-HTTLPR genotype predicts the response to exposure therapy for agoraphobia. Eur Neuropsychopharmacol 2014;24:1222-1228. https://doi.org/10.1016/j.euroneuro.2014.05.007
  10. Maron E, Lang A, Tasa G, Liivlaid L, Toru I, Must A, et al. Associations between serotonin-related gene polymorphisms and panic disorder. Int J Neuropsychopharmacol 2005;8:261-266. https://doi.org/10.1017/S1461145704004985
  11. Samochowiec J, Hajduk A, Samochowiec A, Horodnicki J, Stepien G, Grzywacz A, et al. Association studies of MAO-A, COMT, and 5-HTT genes polymorphisms in patients with anxiety disorders of the phobic spectrum. Psychiatry Res 2004;128:21-26. https://doi.org/10.1016/j.psychres.2004.05.012
  12. Ishiguro H, Arinami T, Yamada K, Otsuka Y, Toru M, Shibuya H. An association study between a transcriptional polymorphism in the serotonin transporter gene and panic disorder in a Japanese population. Psychiatry Clin Neurosci 1997;51:333-335. https://doi.org/10.1111/j.1440-1819.1997.tb03208.x
  13. Kim W, Choi YH, Yoon KS, Cho DY, Pae CU, Woo JM. Tryptophan hydroxylase and serotonin transporter gene polymorphism does not affect the diagnosis, clinical features and treatment outcome of panic disorder in the Korean population. Prog Neuropsychopharmacol Biol Psychiatry 2006;30:1413-1418. https://doi.org/10.1016/j.pnpbp.2006.05.017
  14. Lemonde S, Turecki G, Bakish D, Du L, Hrdina PD, Bown CD, et al. Impaired repression at a 5-hydroxytryptamine 1A receptor gene polymorphism associated with major depression and suicide. J Neurosci 2003;23:8788-8799. https://doi.org/10.1523/JNEUROSCI.23-25-08788.2003
  15. Rothe C, Gutknecht L, Freitag C, Tauber R, Mossner R, Franke P, et al. Association of a functional 1019C>G 5-HT1A receptor gene polymorphism with panic disorder with agoraphobia. Int J Neuropsychopharmacol 2004;7:189-192. https://doi.org/10.1017/S1461145703004061
  16. Lachman HM, Morrow B, Shprintzen R, Veit S, Parsia SS, Faedda G, et al. Association of codon 108/158 catechol-O-methyltransferase gene polymorphism with the psychiatric manifestations of velo-cardio-facial syndrome. Am J Med Genet 1996;67:468-472. https://doi.org/10.1002/(SICI)1096-8628(19960920)67:5<468::AID-AJMG5>3.0.CO;2-G
  17. Domschke K, Deckert J, O'donovan MC, Glatt SJ. Meta-analysis of COMT val158met in panic disorder: ethnic heterogeneity and gender specificity. Am J Med Genet B Neuropsychiatr Genet 2007;144B:667-673. https://doi.org/10.1002/ajmg.b.30494
  18. Woo JM, Yoon KS, Choi YH, Oh KS, Lee YS, Yu BH. The association between panic disorder and the L/L genotype of catechol-Omethyltransferase. J Psychiatr Res 2004;38:365-370. https://doi.org/10.1016/j.jpsychires.2004.01.001
  19. Konishi Y, Tanii H, Otowa T, Sasaki T, Tochigi M, Umekage T, et al. Gene$\times$gene$\times$gender interaction of BDNF and COMT genotypes associated with panic disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2014;51:119-125. https://doi.org/10.1016/j.pnpbp.2014.01.020
  20. Ohara K, Nagai M, Suzuki Y, Ochiai M, Ohara K. No association between anxiety disorders and catechol-O-methyltransferase polymorphism. Psychiatry Res 1998;80:145-148. https://doi.org/10.1016/S0165-1781(98)00062-6
  21. Lim YJ, Yu BH, Kim JH. Korean Panic Disorder Severity Scale: construct validity by confirmatory factor analysis. Depress Anxiety 2007;24:95-102. https://doi.org/10.1002/da.20206
  22. Lee EH, Kim JH, Yu BH. Reliability and validity of the self-report version of the Panic Disorder Severity Scale in Korea. Depress Anxiety 2009;26:E120-E123. https://doi.org/10.1002/da.20461
  23. Shear MK, Rucci P, Williams J, Frank E, Grochocinski V, Vander Bilt J, et al. Reliability and validity of the Panic Disorder Severity Scale: replication and extension. J Psychiatr Res 2001;35:293-296. https://doi.org/10.1016/S0022-3956(01)00028-0
  24. Beck AT, Steer R.A. Manual for the beck anxiety inventory. San Antonio: The Psychological Corporation;1990.
  25. Yook SP, Kim JS. A clinical study on the Korean version of beck anxiety inventory: comparative study of patient and non-patient. Korean J Clin Psychol 1997;16:185-197.
  26. Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J. An inventory for measuring depression. Arch Gen Psychiatry 1961;4:561-571. https://doi.org/10.1001/archpsyc.1961.01710120031004
  27. Rhee MK, Lee YH, Park SH, Sohn CH, Chung YC, Hong SK, et al. A standardization study of Beck Depression Inventory I-Korean version (K-BDI): reliability and factor analysis. Korean J Psychopathol 1995;4:77-95.
  28. Kim B, Yoo E, Lee JY, Lee KS, Choe AY, Lee JE, et al. The effects of the catechol-O-methyltransferase val158met polymorphism on white matter connectivity in patients with panic disorder. J Affect Disord 2013;147:64-71. https://doi.org/10.1016/j.jad.2012.10.009
  29. Choe AY, Kim B, Lee KS, Lee JE, Lee JY, Choi TK, et al. Serotonergic genes (5-HTT and HTR1A) and separation life events: gene-byenvironment interaction for panic disorder. Neuropsychobiology 2013;67:192-200. https://doi.org/10.1159/000347084
  30. Stein MB, Schork NJ, Gelernter J. Gene-by-environment (serotonin transporter and childhood maltreatment) interaction for anxiety sensitivity, an intermediate phenotype for anxiety disorders. Neuropsychopharmacology 2008;33:312-319. https://doi.org/10.1038/sj.npp.1301422
  31. Peter H, Bruckner E, Hand I, Rufer M. Childhood separation anxiety and separation events in women with agoraphobia with or without panic disorder. Can J Psychiatr Nurs 2005;50:941-944. https://doi.org/10.1177/070674370505001409
  32. Lesch KP, Bengel D, Heils A, Sabol SZ, Greenberg BD, Petri S, et al. Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 1996;274:1527-1531. https://doi.org/10.1126/science.274.5292.1527
  33. Heils A, Teufel A, Petri S, Seemann M, Bengel D, Balling U, et al. Functional promoter and polyadenylation site mapping of the human serotonin (5-HT) transporter gene. J Neural Transm Gen Sect 1995;102:247-254. https://doi.org/10.1007/BF01281159
  34. Stoltenberg SF, Christ CC, Carlo G. Afraid to help: social anxiety partially mediates the association between 5-HTTLPR triallelic genotype and prosocial behavior. Soc Neurosci 2013;8:400-406. https://doi.org/10.1080/17470919.2013.807874
  35. Hariri AR, Mattay VS, Tessitore A, Kolachana B, Fera F, Goldman D, et al. Serotonin transporter genetic variation and the response of the human amygdala. Science 2002;297:400-403. https://doi.org/10.1126/science.1071829
  36. Heinz A, Braus DF, Smolka MN, Wrase J, Puls I, Hermann D, et al. Amygdala-prefrontal coupling depends on a genetic variation of the serotonin transporter. Nat Neurosci 2005;8:20-21. https://doi.org/10.1038/nn1366
  37. Pezawas L, Meyer-Lindenberg A, Drabant EM, Verchinski BA, Munoz KE, Kolachana BS, et al. 5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: a genetic susceptibility mechanism for depression. Nat Neurosci 2005;8:828-834. https://doi.org/10.1038/nn1463
  38. Blaya C, Salum GA, Lima MS, Leistner-Segal S, Manfro GG. Lack of association between the Serotonin Transporter Promoter Polymorphism (5-HTTLPR) and Panic Disorder: a systematic review and meta-analysis. Behav Brain Funct 2007;3:41. https://doi.org/10.1186/1744-9081-3-41
  39. Kim H, Lim SW, Kim S, Kim JW, Chang YH, Carroll BJ, et al. Monoamine transporter gene polymorphisms and antidepressant response in Koreans with late-life depression. JAMA 2006;296:1609-1618. https://doi.org/10.1001/jama.296.13.1609
  40. Howe AS, Buttenschon HN, Bani-Fatemi A, Maron E, Otowa T, Erhardt A, et al. Candidate genes in panic disorder: meta-analyses of 23 common variants in major anxiogenic pathways. Mol Psychiatry 2016;21:665-679. https://doi.org/10.1038/mp.2015.138
  41. Shulman R, Griffiths J, Diewold P. Catechol-O-methyl transferase activity in patients with depressive illness and anxiety states. Br J Psychiatry 1978;132:133-138. https://doi.org/10.1192/bjp.132.2.133
  42. Simon NM, Emmanuel N, Ballenger J, Worthington JJ, Kinrys G, Korbly NB, et al. Bupropion sustained release for panic disorder. Psychopharmacol Bull 2003;37:66-72.
  43. Remy P, Doder M, Lees A, Turjanski N, Brooks D. Depression in Parkinson's disease: loss of dopamine and noradrenaline innervation in the limbic system. Brain 2005;128(Pt 6):1314-1322. https://doi.org/10.1093/brain/awh445
  44. Wang M, Ma Y, Yuan W, Su K, Li MD. Meta-Analysis of the COMT Val158Met polymorphism in major depressive disorder: effect of ethnicity. J Neuroimmune Pharmacol 2016;11:434-445. https://doi.org/10.1007/s11481-016-9651-3
  45. Kang JI, Kim SJ, Song YY, Namkoong K, An SK. Genetic influence of COMT and BDNF gene polymorphisms on resilience in healthy college students. Neuropsychobiology 2013;68:174-180. https://doi.org/10.1159/000353257
  46. Kim YR, Kim JH, Kim SJ, Lee D, Min SK. Catechol-O-methyltransferase Val158Met polymorphism in relation to aggressive schizophrenia in a Korean population. Eur Neuropsychopharmacol 2008;18:820-825. https://doi.org/10.1016/j.euroneuro.2008.07.009
  47. Mattay VS, Goldberg TE, Fera F, Hariri AR, Tessitore A, Egan MF, et al. Catechol O-methyltransferase val158-met genotype and individual variation in the brain response to amphetamine. Proc Natl Acad Sci U S A 2003;100:6186-6191. https://doi.org/10.1073/pnas.0931309100
  48. Gallinat J, Senkowski D, Wernicke C, Juckel G, Becker I, Sander T, et al. Allelic variants of the functional promoter polymorphism of the human serotonin transporter gene is associated with auditory cortical stimulus processing. Neuropsychopharmacology 2003;28:530-532. https://doi.org/10.1038/sj.npp.1300042
  49. Dudbridge F, Gusnanto A. Estimation of significance thresholds for genomewide association scans. Genet Epidemiol 2008;32:227-234. https://doi.org/10.1002/gepi.20297
  50. Qu HQ, Tien M, Polychronakos C. Statistical significance in genetic association studies. Clin Invest Med 2010;33:E266-E270. https://doi.org/10.25011/cim.v33i5.14351