The role of the brain-derived neurotrophic factor (BDNF) val66met variant in the phenotypic expression of Obsessive-Compulsive Disorder (OCD)

American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics

Volumn 150, Issue 8, 2009, Pages 1050-1062

  Katerberg, Hilga ^a,b   Lochner, Christine ^c   Cath, Danielle C ^b,d   De Jonge, Peter ^a   Bochdanovits, Zoltán ^b,e   Moolman Smook, Johanna C ^c   Hemmings, Sîan M J ^c   Carey, Paul D ^c   Stein, Dan J ^c,f   Sondervan, David ^b   Den Boer, Johan A ^a   Van Balkom, Anton J L M ^b,d   Polman, Annemiek ^a   Heutink, Peter ^b,e  

^a UNIVERSITY MEDICAL CENTER GRONINGEN   (Netherlands)

^b VU UNIVERSITY MEDICAL CENTER   (Netherlands)

^c STELLENBOSCH UNIVERSITY   (South Africa)

^d GGZ Foundation for Mental Health Care Buitenamstel   (Netherlands)

^e VU UNIVERSITY AMSTERDAM   (Netherlands)

^f UNIVERSITY OF CAPE TOWN   (South Africa)

Author keywords

Age of onset; Item level factor analysis; Obsessive compulsive disorder; Symptom dimensions; Yale Brown obsessive compulsive scale severity

Indexed keywords

ADULT; ARTICLE; BDNF GENE; CASE CONTROL STUDY; CONTROLLED STUDY; DISEASE SEVERITY; FAMILY HISTORY; FEMALE; GENE; GENETIC ASSOCIATION; GENETIC POLYMORPHISM; GENOTYPE PHENOTYPE CORRELATION; HUMAN; MAJOR CLINICAL STUDY; MALE; OBSESSIVE COMPULSIVE DISORDER; ONSET AGE; PRIORITY JOURNAL;

ADULT; AGE OF ONSET; BRAIN-DERIVED NEUROTROPHIC FACTOR; CASE-CONTROL STUDIES; FAMILY HEALTH; FEMALE; GENETIC ASSOCIATION STUDIES; GENOTYPE; HUMANS; MALE; MIDDLE AGED; MUTATION, MISSENSE; OBSESSIVE-COMPULSIVE DISORDER; PHENOTYPE; PSYCHIATRIC STATUS RATING SCALES; SEVERITY OF ILLNESS INDEX; SEX FACTORS; YOUNG ADULT;

EID: 72049131287     PISSN: 15524841     EISSN: 1552485X     Source Type: Journal    
DOI: 10.1002/ajmg.b.30930     Document Type: Article

References (63)

1. Alonso P, Gratacos M, Menchon JM, Saiz-Ruiz J, Segalas C, Baca-Garcia E, Labad J, Fernandez-Piqueras J, Real E, Vaquero C, Perez M, Dolengevich H, Gonzalez JR, Bayes M, de Cid R, Vallejo J, Estivill X. 2008. Extensive genotyping of the BDNF and NTRK2 genes define protective haplotypes against obsessive-compulsive disorder. Biol Psychiatry 63:619-628. (Pubitemid 351273192)
2. Alsobrook IJ, Leckman JF, Goodman WK, Rasmussen SA, Pauls DL. 1999. Segregation analysis of obsessive-compulsive disorder using symptom-based factor scores. Am J Med Genet (Neuropsychiatr Genet) 88: 669-675.
3. American Psychiatric Association. 1994. Diagnostic and statistical manual of mental disorders, 4th edition. Washington, DC:American Psychiatric Association.
4. Angst J, Gamma A, Endrass J, Goodwin R, Ajdacic V, Eich D, Rossler W. 2004. Obsessive-compulsive severity spectrum in the community: Prevalence, comorbidity, and course. Eur Arch Psychiatry Clin Neurosci 254:156-164. (Pubitemid 39304465)
5. Browne MW, Cudek R. 1993. Alternative ways of assessing model fit. In: Bollen KA, Long JS, editors. Testing structural equation models. Newbury Park, CA:Sage. pp 136-162.
6. Carvalho AL, Caldeira MV, Santos SD, Duarte CB. 2008. Role of the brain-derived neurotrophic factor at glutaminergic synapses. Br J Psychiatry 153:S310-S324. (Pubitemid 351340985)
7. Cavallini MC, Di Bella D, Siliprandi F, Malchiodi F, Bellodi L. 2002. Exploratory factor analysis of obsessive-compulsive patients and association with 5-HTTLPR polymorphism. Am J Med Genet (Neuropsychiatr Genet) 114:347-353. (Pubitemid 34262689)
8. Chen ZY, Jing D, Bath KG, Ieraci A, Khan T, Siao CJ, Herrera DG, Toth M, Yang C, McEwen BS, Hempstead BL, Lee FS. 2006. Genetic variant BDNF (Val66Met) polymorphism alters anxiety-related behavior. Science 314: 140-143. (Pubitemid 44547760)
9. Daws LC, Munn JL, Valdez MF, Frosto-Burke T, Hensler JG. 2007. Serotonin transporter function, but not expression, is dependent on brain-derived neurotrophic factor (BDNF): In vivo studies in BDNF-deficient mice. J Neurochem 101:641-651.
10. Delorme R, Golmard JL, Chabane N, Millet B, Krebs MO, Mouren-Simeoni MC, Leboyer M. 2005. Admixture analysis of age at onset in obsessive-compulsive disorder. Psychol Med 35:237-243. (Pubitemid 40259915)
11. Dickel DE, Veenstra-VanderWeele J, Bivens NC, Wu X, Fischer DJ, Van Etten-Lee M, Himle JA, Leventhal BL, Cook EH Jr, Hanna GL. 2007. Association studies of serotonin system candidate genes in early-onset obsessive-compulsive disorder. Biol Psychiatry 61:322-329. (Pubitemid 46108693)
12. Egan MF, Kojima M, Callicott JH, Goldberg TE, Kolachana BS, Bertolino A, Zaitsev E, Gold B, Goldman D, Dean M, Lu B, Weinberger DR. 2003. The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell 112: 257-269. (Pubitemid 36144114)
13. First MB, Spitzer RL, Gobbon M, Williams JBW. 1998. Structured clinical interview for DSM-IV Axis 1 disorders - Patient Edition (SCID-I/P, Version 2.0, 8/98 revision). New York:New York State Psychiatric Instistute. Biometrics department.
14. Fontenelle LF, Mendlowicz MV, Marques C, Versiani M. 2003. Early- and late-onset obsessive-compulsive disorder in adult patients: An exploratory clinical and therapeutic study. J Psychiatr Res 37:127-133. (Pubitemid 36808475)
15. Goodman WK, Price LH, Rasmussen SA, Mazure C, Delgado P, Heninger GR, Charney DS. 1989a. The Yale-Brown obsessive compulsive scale. II. Validity. Arch Gen Psychiatry 46:1012-1016.
16. Goodman WK, Price LH, Rasmussen SA, Mazure C, Fleischmann RL, Hill CL, Heninger GR, Charney DS. 1989b. The Yale-Brown obsessive compulsive scale. I. Development, use, and reliability. Arch Gen Psychiatry 46:1006-1011.
17. Hall D, Dhilla A, Charalambous A, Gogos JA, Karayiorgou M. 2003. Sequence variants of the brain-derived neurotrophic factor (BDNF) gene are strongly associated with obsessive-compulsive disorder. Am J Hum Genet 73:370-376. (Pubitemid 36920998)
18. Hasler G, Kazuba D, Murphy DL. 2006. Factor analysis of obsessive-compulsive disorder YBOCS-SC symptoms and association with 5-HTTLPR SERT polymorphism. Am J Med Genet Part B 141B:403-408. (Pubitemid 43872894)
19. Hasler G, Pinto A, Greenberg BD, Samuels J, Fyer AJ, Pauls D, Knowles JA, McCracken JT, Piacentini J, Riddle MA, Rauch SL, Rasmussen SA, Willour VL, Grados MA, Cullen B, Bienvenu OJ, Shugart YY, Liang KY, Hoehn-Saric R, Wang Y, Ronquillo J, Nestadt G, Murphy DL. 2007. Familiality of factor analysis-derived YBOCS dimensions in OCD-affected sibling pairs from the OCD Collaborative Genetics Study. Biol Psychiatry 61:617-625. (Pubitemid 46328863)
20. Hemmings SM, Kinnear CJ, Van Der Merwe L, Lochner C, Corfield VA, Moolman-Smook JC, Stein DJ. 2008. Investigating the role of the brain-derived neurotrophic factor (BDNF) val66met variant in obsessivecompulsive disorder (OCD). World J Biol Psychiatry 9:126-134. (Pubitemid 351567037)
21. Hennigan A, O'Callaghan RM, Kelly AM. 2007. Neurotrophins and their receptors: Roles in plasticity, neurodegeneration and neuroprotection. Biochem Soc Trans 35:424-427. (Pubitemid 46596521)
22. Hettema JM, Neale MC, Kendler KS. 2001. A review and meta-analysis of the genetic epidemiology of anxiety disorders. Am J Psychiatry 158: 1568-1578. (Pubitemid 32923644)
23. Hiroi R, McDevitt RA, Neumaier JF. 2006. Estrogen selectively increases tryptophan hydroxylase-2mRNA expression in distinct subregions of rat midbrain raphe nucleus: Association between gene expression and anxiety behavior in the open field. Biol Psychiatry 60:288-295. (Pubitemid 44093439)
24. Hu L, Bentler PM. 1999. Cutoff criteria for fit indexes in covariance structure analysis: Conventional criteria versus new alternatives. Struct Equation Model 6:1-55.
25. Imwalle DB, Gustafsson JA, Rissman EF. 2005. Lack of functional estrogen receptor beta influences anxiety behavior and serotonin content in female mice. Physiol Behav 84:157-163.
26. Kaufman J, Yang BZ, Douglas-Palumberi H, Grasso D, Lipschitz D, Houshyar S, Krystal JH, Gelernter J. 2006. Brain-derived neurotrophic factor-5-HTTLPR gene interactions and environmental modifiers of depression in children. Biol Psychiatry 59:673-680.
27. Kim SJ, Lee HS, Kim CH. 2005. Obsessive-compulsive disorder, factoranalyzed symptom dimensions and serotonin transporter polymorphism. Neuropsychobiology 52:176-182. (Pubitemid 41677016)
28. Kim JM, Stewart R, Kim SW, Yang SJ, Shin IS, Kim YH, Yoon JS. 2007. Interactions between life stressors and susceptibility genes (5-HTTLPR and BDNF) on depression in Korean elders. Biol Psychiatry 62:423-428. (Pubitemid 47284032)
29. Klaffke S, Konig IR, Poustka F, Ziegler A, Hebebrand J, Bandmann O. 2006. Brain-derived neurotrophic factor: A genetic risk factor for obsessive-compulsive disorder and Tourette syndrome? Mov Disord 21:881-883.
30. Labad J, Menchon JM, Alonso P, Segalas C, Jimenez S, Jaurrieta N, Leckman JF, Vallejo J. 2008. Gender differences in obsessive-compulsive symptom dimensions. Depress Anxiety 25:832-838.
31. Leckman JF, Pauls DL, Zhang H, Rosario-Campos MC, Katsovich L, Kidd KK, Pakstis AJ, Alsobrook JP, Robertson MM, McMahon WM, Walkup JT, van de Wetering BJ, King RA, Cohen DJ. 2003. Obsessive-compulsive symptom dimensions in affected sibling pairs diagnosed with Gilles de la Tourette syndrome. Am J Med Genet Part B 116B:60-68. (Pubitemid 37063616)
32. Lenane MC, Swedo SE, Leonard H, Pauls DL, Sceery W, Rapoport JL. 1990. Psychiatric disorders in first degree relatives of children and adolescents with obsessive compulsive disorder. J Am Acad Child Adolesc Psychiatry 29:407-412. (Pubitemid 20208420)
33. Lochner C, Hemmings SM, Kinnear CJ, Moolman-Smook JC, Corfield VA, Knowles JA, Niehaus DJ, Stein DJ. 2004. Gender in obsessive-compulsive disorder: Clinical and genetic findings. Eur Neuropsychopharmacol 14:105-113. (Pubitemid 38175427)
34. Lochner C, Hemmings SM, Kinnear CJ, Nel D, Seedat S, Moolman-Smook JC, Stein DJ. 2008. Cluster analysis of obsessive-compulsive symptomatology: Identifying obsessive-compulsive disorder subtypes. Isr J Pyschiatry Relat Sci 45:164-176.
35. MacCallum RC, Widaman KF, Zhang S, Hong S. 1999. Sample size in factor analysis. Psychol Methods 4:84-99.
36. Meulenbelt I, Droog S, Trommelen GJ, Boomsma DI, Slagboom PE. 1995. High-yield noninvasive human genomic DNA isolation method for genetic studies in geographically dispersed families and populations. Am J Hum Genet 57:1252-1254.
37. Miguel EC, Leckman JF, Rauch S, do Rosario-Campos MC, Hounie AG, Mercadante MT, Chacon P, Pauls DL. 2005. Obsessive-compulsive disorder phenotypes: Implications for genetic studies. Mol Psychiatry 10:258-275.
38. Miller SA, Dykes DD, Polesky HF. 1988. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16:1215.
39. Mossner R, Daniel S, Albert D, Heils A, Okladnova O, Schmitt A, Lesch KP. 2000. Serotonin transporter function is modulated by brain-derived neurotrophic factor (BDNF) but not nerve growth factor (NGF). Neurochem Int 36:197-1202.
40. Mossner R, Walitza S, Lesch KP, Geller F, Barth N, Remschmidt H, Hahn F, Herpertz-Dahlmann B, Fleischhaker C, Schulz E, Warnke A, Hinney A, Wewetzer C. 2005. Brain-derived neurotrophic factor V66M polymorphism in childhood-onset obsessive-compulsive disorder. Int J Neuropsychopharmacol 8:133-136. (Pubitemid 40388821)
41. Muthén LK, Muthén B. 1998-2006. Mplus user's guide, 4th edition. Los Angeles, CA:Muthén & Muthén.
42. Nestadt G, Samuels JF, Riddle MA, Bienvenu OJ, Liang KY, Grados MA, Cullen B. 2002. Obsessive-compulsive disorder: Defining the phenotype. J Clin Psychiatry 63(Suppl 6): 5-7.
43. Pauls DL, Alsobrook JP II. 1999. The inheritance of obsessive-compulsive disorder. Child Adolesc Psychiatr Clin N Am 8:481-496, viii.
44. Pauls DL, Alsobrook JP II, Goodman W, Rasmussen S, Leckman JF. 1995.A family study of obsessive-compulsive disorder. Am J Psychiatry 152: 76-84.
45. Pittenger C, Krystal JH, Coric V. 2006. Glutamate-modulating drugs as novel pharmacotherapeutic agents in the treatment of obsessive-compulsive disorder. NeuroRx 3:69-81. (Pubitemid 43276634)
46. Pritchard JK, Donnelly P. 2001. Case-control studies of association in structured or admixed populations. Theor Popul Biol 60:227-237. (Pubitemid 34235093)
47. Purcell S, Cherny SS, Sham PC. 2003. Genetic Power Calculator: Design of linkage and association genetic mapping studies of complex traits. Bioinformatics 19:149-150. (Pubitemid 36150192)
48. R Development Core Team. 2008. A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing. http://www.R-project.org.
49. Ren-Patterson RF, Cochran LW, Holmes A, Lesch KP, Lu B, Murphy DL. 2006. Gender-dependent modulation of brain monoamines and anxiety-like behaviors in mice with genetic serotonin transporter and BDNF deficiencies. Cell Mol Neurobiol 26:755-780.
50. Samuels J, Shugart YY, Grados MA, Willour VL, Bienvenu OJ, Greenberg BD, Knowles JA, McCracken JT, Rauch SL, Murphy DL, Wang Y, Pinto A, Fyer AJ, Piacentini J, Pauls DL, Cullen B, Rasmussen SA, Hoehn-Saric R, Valle D, Liang KY, Riddle MA, Nestadt G. 2007. Significant linkage to compulsive hoarding on chromosome 14 in families with obsessive-compulsive disorder: Results from the OCD Collaborative Genetics Study. Am J Psychiatry 164:493-499. (Pubitemid 46513164)
51. Schafer JL. 1999. Multiple imputation: A primer. Stat Methods Med Res 8:3-15.
52. Schulze TG, McMahon FJ. 2002. Genetic association mapping at the crossroads: Which test and why? Overview and practical guidelines. Am J Med Genet (Neuropsychiatr Genet) 114:1-11.
53. Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, Hergueta T, Baker R, Dunbar GC. 1998. The Mini-International Neuropsychiatric Interview (M.I.N.I.): The development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry 59(Suppl 20): 22-33; quiz 34-57.
54. Silverman EK, Palmer LJ. 2000. Case-control association studies for the genetics of complex respiratory diseases. Am J Respir Cell Mol Biol 22:645-648.
55. Sobin C, Blundell ML, Karayiorgou M. 2000. Phenotypic differences in early- and late-onset obsessive-compulsive disorder. Compr Psychiatry 41:373-379. (Pubitemid 30696435)
56. Steketee G, Frost R, Bogart K. 1996. The Yale-Brown obsessive compulsive scale: Interview versus self-report. Behav Res Ther 34:675-684. (Pubitemid 26316913)
57. Thomas DC, Witte JS. 2002. Point: Population stratification:Aproblem for case-control studies of candidate-gene associations? Cancer Epidemiol Biomarkers Prev 11:505-512.
58. van Grootheest DS, Cath DC, Beekman AT, Boomsma DI. 2005. Twin studies on obsessive-compulsive disorder: A review. Twin Res Hum Genet 8:450-458. (Pubitemid 41499486)
59. Weissman MM, Bland RC, Canino GJ, Greenwald S, Hwu HG, Lee CK, Newman SC, Oakley-Browne MA, Rubio-Stipec M, Wickramaratne PJ, et al. 1994. The cross national epidemiology of obsessive compulsive disorder. The Cross National Collaborative Group. J Clin Psychiatry 55(Suppl):5-10.
60. Wendland JR, Kruse MR, Cromer KC, Murphy DL. 2007. A large casecontrol study of common functional SLC6A4 and BDNF variants in obsessive-compulsive disorder. Neuropsychopharmacology 32:2543-2551.
61. Westenberg HG, Fineberg NA, Denys D. 2007. Neurobiology of obsessivecompulsive disorder: Serotonin and beyond. CNS Spectr 12:14-27.
62. Zai G, Arnold P, Strauss J, King N, Burroughs E, Richter MA, Kennedy JL. 2005. No association between brain-derived neurotrophic factor gene and obsessive-compulsive disorder. Psychiatr Genet (Neuropsychiatr Genet) 15:235. (Pubitemid 44491458)
63. Zhang H, Leckman JF, Pauls DL, Tsai CP, Kidd KK, Campos MR. 2002. Genomewide scan of hoarding in sib pairs in which both sibs have Gilles de la Tourette syndrome. Am J Hum Genet 70:896-904. (Pubitemid 34259306)