Association between the GRIN2B Gene and Age of Onset in Obsessive-Compulsive Disorder

글루타메이트 수용체(GRIN2B) 유전자와 강박장애 발병 연령과의 관련성

  • 황성식 (평내 정신과의원) ;
  • 노대영 (연세대학교 의과대학 정신과학교실) ;
  • 김찬형 (연세대학교 의과대학 정신과학교실)
  • Received : 2011.03.15
  • Accepted : 2011.04.18
  • Published : 2011.04.30

Abstract

Objectives : An early age at onset of obsessive compulsive symptoms in family studies has been strongly associated with a more familial form of obsessive compulsive disorder (OCD). Further, many reports have suggested that early- and late- onset OCD represent separate subtypes of the disorder. The aim of this study was to investigate the associations between the glutamate receptor, the ionotropic, n-methyl-d-aspartate (NMDA) subunit 2B gene (GRIN2B) polymorphisms, and onset of OCD in the Korean population. Methods : We recruited 109 OCD patients and classified them into early- (age of onset <18 years) and late-onset groups (age of onset${\geq}$18). Genomic DNA was extracted from their blood after which the genotypes and allelic frequencies of the two GRIN2B polymorphisms (5072T/G and 5988T/C) were compared in the two groups. We also compared genetic data between child- (age of onset${\leq}$15) and adult-onset groups (age of onset${\geq}$19) using the same protocol. Results : There were no significant differences between the early- and late-onset groups with respect to genotype. Moreover, we could not find any differences in genotype frequencies between child and adult-onset groups. Conclusions : Our study suggested that GRIN2B polymorphisms (5072T/G and 5988T/C) do not affect the onset of OCD in Koreans. However, this finding has resulted from a preliminary study and thus, further study is required.

Keywords

References

  1. Leckman JF, Grice DE, Boardman J, Zhang H, Vitale A, Bondi C, et al. Symptoms of obsessive-compulsive disorder. Am J Psychiatry 1997;154:911-917. https://doi.org/10.1176/ajp.154.7.911
  2. Cavallini MC, Di Bella D, Siliprandi F, Malchiodi F, Bellodi L. Exploratory factor analysis of obsessive-compulsive patients and association with 5-HTTLPR polymorphism. Am J Med Genet 2002; 114:347-353. https://doi.org/10.1002/ajmg.1700
  3. Pauls DL, Alsobrook JP 2nd, Goodman W, Rasmussen S, Leckman JF. A family study of obsessive-compulsive disorder. Am J Psychiatry 1995;152:76-84. https://doi.org/10.1176/ajp.152.1.76
  4. Inouye E. Similar and Dissimilar Manifestations of Obsessive-Compulsive Neuroses in Monozygotic Twins. Am J Psychiatry 1965;121: 1171-1175. https://doi.org/10.1176/ajp.121.12.1171
  5. Cavallini MC, Pasquale L, Bellodi L, Smeraldi E. Complex segregation analysis for obsessive compulsive disorder and related disorders. Am J Med Genet 1999;88:38-43. https://doi.org/10.1002/(SICI)1096-8628(19990205)88:1<38::AID-AJMG7>3.0.CO;2-#
  6. Zohar AH, Pauls DL, Ratzoni G, Apter A, Dycian A, Binder M, et al. Obsessive-compulsive disorder with and without tics in an epidemiological sample of adolescents. Am J Psychiatry 1997;154:274-276. https://doi.org/10.1176/ajp.154.2.274
  7. Swedo SE, Rapoport JL, Leonard H, Lenane M, Cheslow D. Obsessive- compulsive disorder in children and adolescents. Clinical phenomenology of 70 consecutive cases. Arch Gen Psychiatry 1989; 46:335-341. https://doi.org/10.1001/archpsyc.1989.01810040041007
  8. Delorme R, Golmard J, Chabane N, Millet B, Krebs M, Mouren-Simeoni MC, et al. Admixture analysis of age at onset in obsessive-compulsive disorder. Psychol Med 2005;35:237-243. https://doi.org/10.1017/S0033291704003253
  9. Zohar J, Chopra M, Sasson Y, Amiaz R, Amital D. Obsessive compulsive disorder: serotonin and beyond. World J Biol Psychiatry 2000; 1:92-100. https://doi.org/10.3109/15622970009150571
  10. Greist JH, Jefferson JW, Kobak KA, Katzelnick DJ, Serlin RC. Efficacy and tolerability of serotonin transport inhibitors in obsessive-compulsive disorder. A meta-analysis. Arch Gen Psychiatry 1995;52: 53-60. https://doi.org/10.1001/archpsyc.1995.03950130053006
  11. McDougle CJ, Goodman WK, Leckman JF, Lee NC, Heninger GR, Price LH. Haloperidol addition in fluvoxamine-refractory obsessive- compulsive disorder. A double-blind, placebo-controlled study in patients with and without tics. Arch Gen Psychiatry 1994;51:302-308. https://doi.org/10.1001/archpsyc.1994.03950040046006
  12. Pian KL, Westenberg HG, van Megen HJ, den Boer JA. Sumatriptan (5-HT1D receptor agonist) does not exacerbate symptoms in obsessive compulsive disorder. Psychopharmacology 1998;140:365-370. https://doi.org/10.1007/s002130050777
  13. Khanna S, John JP, Reddy LP. Neuroendocrine and behavioral responses to mCPP in Obsessive-Compulsive Disorder. Psychoneuroendocrinology 2001;26:209-223. https://doi.org/10.1016/S0306-4530(00)00048-2
  14. Rosenberg DR, MacMaster FP, Keshavan MS, Fitzgerald KD, Stewart CM, Moore GJ. Decrease in caudate glutamatergic concentrations in pediatric obsessive-compulsive disorder patients taking paroxetine. J Am Acad Child Adolesc Psychiatry 2000;39:1096-1103. https://doi.org/10.1097/00004583-200009000-00008
  15. Maione S, Rossi F, Biggs CS, Fowler LJ, Whitton PS. AMPA receptors modulate extracellular 5-hydroxytryptamine concentration and metabolism in rat striatum in vivo. Neurochem Int 1997;30:299-304. https://doi.org/10.1016/S0197-0186(96)00101-5
  16. Jan de Beur SM, Ding CL, LaBuda MC, Usdin TB, Levine MA. Pseudohypoparathyroidism 1b: exclusion of parathyroid hormone and its receptors as candidate disease genes. J Clin Endocrinol Metab 2000;85:2239-2246. https://doi.org/10.1210/jc.85.6.2239
  17. Loftis JM, Janowsky A. The N-methyl-D-aspartate receptor subunit NR2B: localization, functional properties, regulation, and clinical implications. Pharmacol Ther 2003;97:55-85. https://doi.org/10.1016/S0163-7258(02)00302-9
  18. Laurie DJ, Bartke I, Schoepfer R, Naujoks K, Seeburg PH. Regional, developmental and interspecies expression of the four NMDAR2 subunits, examined using monoclonal antibodies. Brain Res Mol Brain Res 1997;51:23-32. https://doi.org/10.1016/S0169-328X(97)00206-4
  19. Rauch S, Whalen P, Dougherty D, Jenike M. Neurobiologic models of obsessive-compulsive disorder. In: Jenike M, Baer L, Minichiello W, editors. Obsessive-compulsive disorders: practical management. St Louis: Mosby;1998. p.222-253.
  20. Spitzer RL, Williams JB, Gibbon M, First MB. The Structured Clinical Interview for DSM-III-R (SCID). I: History, rationale, and description. Arch Gen Psychiatry 1992;49:624-629. https://doi.org/10.1001/archpsyc.1992.01820080032005
  21. Rosario-Campos MC, Leckman JF, Mercadante MT, Shavitt RG, Prado HS, Sada P, et al. Adults with early-onset obsessive-compulsive disorder. Am J Psychiatry 2001;158:1899-1903. https://doi.org/10.1176/appi.ajp.158.11.1899
  22. Hemmings SM, Kinnear CJ, Lochner C, Niehaus DJ, Knowles JA, Moolman-Smook JC, et al. Early- versus late-onset obsessive-compulsive disorder: investigating genetic and clinical correlates. Psychiatry Res 2004;128:175-182. https://doi.org/10.1016/j.psychres.2004.05.007
  23. Goodman WK, Price LH, Rasmussen SA, Mazure C, Fleischmann RL, Hill CL, et al. The Yale-Brown Obsessive Compulsive Scale. I. Development, use, and reliability. Arch Gen Psychiatry 1989;46: 1006-1011. https://doi.org/10.1001/archpsyc.1989.01810110048007
  24. Hamilton M. Development of a rating scale for primary depressive illness. Br J Soc Clin Psychol 1967;6:278-296. https://doi.org/10.1111/j.2044-8260.1967.tb00530.x
  25. Dickel DE, Veenstra-VanderWeele J, Cox NJ, Wu X, Fischer DJ, Van Etten-Lee M, et al. Association testing of the positional and functional candidate gene SLC1A1/EAAC1 in early-onset obsessive- compulsive disorder. Arch Gen Psychiatry 2006;63:778-785. https://doi.org/10.1001/archpsyc.63.7.778
  26. Arnold PD, Macmaster FP, Richter MA, Hanna GL, Sicard T, Burroughs E, et al. Glutamate receptor gene (GRIN2B) associated with reduced anterior cingulate glutamatergic concentration in pediatric obsessive-compulsive disorder. Psychiatry Res 2009;172:136-139. https://doi.org/10.1016/j.pscychresns.2009.02.005
  27. Arnold PD, Rosenberg DR, Mundo E, Tharmalingam S, Kennedy JL, Richter MA. Association of a glutamate (NMDA) subunit receptor gene (GRIN2B) with obsessive-compulsive disorder: a preliminary study. Psychopharmacology 2004;174:530-538.
  28. Fontenelle LF, Mendlowicz MV, Marques C, Versiani M. Early- and late-onset obsessive-compulsive disorder in adult patients: an exploratory clinical and therapeutic study. J Psychiatr Res 2003;37: 127-133. https://doi.org/10.1016/S0022-3956(02)00087-0
  29. Busatto GF, Buchpiguel CA, Zamignani DR, Garrido GE, Glabus MF, Rosario-Campos MC, et al. Regional cerebral blood flow abnormalities in early-onset obsessive-compulsive disorder: an exploratory SPECT study. J Am Acad Child Adolesc Psychiatry 2001;40: 347-354. https://doi.org/10.1097/00004583-200103000-00015
  30. Bogetto F, Venturello S, Albert U, Maina G, Ravizza L. Gender-related clinical differences in obsessive-compulsive disorder. Eur Psychiatry 1999;14:434-441. https://doi.org/10.1016/S0924-9338(99)00224-2
  31. Karno M, Golding JM, Sorenson SB, Burnam MA. The epidemiology of obsessive-compulsive disorder in five US communities. Arch Gen Psychiatry 1988;45:1094-1099. https://doi.org/10.1001/archpsyc.1988.01800360042006
  32. Zohar J, Gross-Isseroff R, Hermesh H, Weizman A. Is there sexual dimorphism in obsessive-compulsive disorder? Neurosci Biobehav Rev 1999;23:845-849. https://doi.org/10.1016/S0149-7634(99)00021-4
  33. Lee H, Namkoong K, Lee M, Min S, Kim S, Song D, et al. Epidemiologic study of psychiatry in Kang-Hwa Do (III) - Life time prevalence of major psychiatric disorders. J Korean Neuropsychiatr Assoc 1989;28:984-999.
  34. Lee J. Epidemiologic study of psychiatric disorder in Korea (XII)- Prevalence of obsessive compulsive disorder. J Korean Neuropsychiatr Assoc 1994;33:5-17.
  35. Kim C, KA. C, Koo M, Nam Y, Hong C, Lee H. Clinical characteristics and courses in patients with early-onset and late-onset obsessive- compulsive disorder. Korean J Psychopharmacol 2003;14:163-171.
  36. Kwon J, Lee D, Yoon D. Clinical characteristics of obsessive-compulsive disorder (Inpatient record study). J Korean Neuropsychiatr Assoc 1998;37:225-233.
  37. Albert U, Picco C, Maina G, Forner F, Aguglia E, Bogetto F. [Phenomenology of patients with early and adult onset obsessive-compulsive disorder]. Epidemiol Psichiatr Soc 2002;11:116-126. https://doi.org/10.1017/S1121189X00005571