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Meta-analysis of the association of brain-derived neurotrophic factor Val66Met polymorphism with obsessive–compulsive disorder

Published online by Cambridge University Press:  04 June 2015

Jun Wang
Affiliation:
Department of Clinical Psychiatry, Wuxi Mental Health Center, Nanjing Medical University, Wuxi, Jiangsu Province, China
Fuquan Zhang
Affiliation:
Department of Clinical Psychology, Wuxi Mental Health Center, Nanjing Medical University, Wuxi, Jiangsu Province, China
Wenxian Zhu
Affiliation:
Department of Clinical Psychiatry, Wuxi Mental Health Center, Nanjing Medical University, Wuxi, Jiangsu Province, China
Yansong Liu
Affiliation:
Department of Clinical Psychology, Wuxi Mental Health Center, Nanjing Medical University, Wuxi, Jiangsu Province, China
Zhenhe Zhou
Affiliation:
Department of Clinical Psychiatry, Wuxi Mental Health Center, Nanjing Medical University, Wuxi, Jiangsu Province, China
Corresponding
E-mail address:

Abstract

Objective

Brain-derived neurotrophic factor (BDNF) plays an important role in neural survival and was proposed to be related to psychiatric disorders. Val66Met (also known as rs6265 or G196A), the only known functional polymorphism of the BDNF gene, has been widely studied and considered to be associated with risk of some psychiatric disorders such as bipolar disorder and schizophrenia. However, studies evaluating its association with obsessive–compulsive disorder (OCD) obtained inconsistent results. The purpose of this study was to derive a more precise estimation of the association between BDNF Val66Met polymorphism and OCD susceptibility by a meta-analysis.

Method

We carried a structured literature search in PubMed, Embase, PsycINFO and Chinese Biomedical Database up to December 2014; and retrieved all eligible case–control studies according to the including criteria. Meta-analysis was performed for four genetic models: allelic model: Met versus Val; additive model: Met/Met versus Val/Val; recessive model: Met/Met versus Val/Val+Val/Met; and dominant model: Val/Met+Met/Met versus Val/Val. Stratified analyses were performed by ethnicity and gender where appropriate.

Results

A total of eight articles with nine studies including 1632 OCD cases and 2417 controls were identified. No significant association was detected in any comparison when the whole data were pooled together or stratified by ethnicity or gender in all four genetic models (p>0.05 for each comparison).

Conclusion

Despite some limitations, our meta-analysis suggests that no significant association exists between the BDNF Val66Met polymorphism and OCD susceptibility.

Type
Original Articles
Copyright
© Scandinavian College of Neuropsychopharmacology 2015 

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References

1. Murray, CJ, Lopez, AD. The global burden of disease. Cambridge: Harvard University Press, 1996.Google ScholarPubMed
2. Sasson, Y, Zohar, J, Chopra, M, Lustig, M, Iancu, I, Hendler, T. Epidemiology of obsessive-compulsive disorder: a world view. J Clin Psychiatry 1997;58(Suppl. 12):710.Google ScholarPubMed
3. Karno, M, Golding, JM, Sorenson, SB, Burnam, MA. The epidemiology of obsessive-compulsive disorder in five US communities. Arch Gen Psychiatry 1998;45:10941099.CrossRefGoogle ScholarPubMed
4. Ruscio, AM, Stein, DJ, Chiu, WT, Kessler, RC. The epidemiology of obsessive-compulsive disorder in the National Comorbidity Survey Replication. Mol Psychiatry 2010;15:5363.CrossRefGoogle ScholarPubMed
5. Mundo, E, Richter, MA, Zai, G et al. 5HT1Dbeta receptor gene implicated in the pathogenesis of obsessive-compulsive disorder: further evidence from a family-based association study. Mol Psychiatry 2002;7:805809.CrossRefGoogle ScholarPubMed
6. Arnold, PD, Sicard, T, Burroughs, E, Richter, MA, Kennedy, JL. Glutamate transporter gene SLC1A1 associated with obsessive-compulsive disorder. Arch Gen Psychiatry 2006;63:769776.CrossRefGoogle ScholarPubMed
7. Billett, EA, Richter, MA, King, N, Heils, A, Lesch, KP, Kennedy, JL. Obsessive compulsive disorder, response to serotonin reuptake inhibitors and the serotonin transporter gene. Mol Psychiatry 1997;2:403406.CrossRefGoogle ScholarPubMed
8. Guillin, O, Diaz, J, Carroll, P, Griffon, N, Schwartz, JC, Sokoloff, P. BDNF controls dopamine D3 receptor expression and triggers behavioural sensitization. Nature 2001;411:8689.CrossRefGoogle ScholarPubMed
9. Wozniak, W. Brain-derived neurotrophic factor (BDNF): role in neuronal development and survival. Folia Morphol (Warsz) 1993;52:173181.Google Scholar
10. Mossner, R, Daniel, S, Albert, D et al. Serotonin transporter function is modulated by brain-derived neurotrophic factor (BDNF) but not nerve growth factor (NGF). Neurochem Int 2000;36:197202.CrossRefGoogle Scholar
11. Angelucci, F, Brene, S, Mathe, AA. BDNF in schizophrenia, depression and corresponding animal models. Mol Psychiatry 2005;10:345352.CrossRefGoogle Scholar
12. Wang, Y, Mathews, CA, Li, Y, Lin, Z, Xiao, Z. Brain-derived neurotrophic factor (BDNF) plasma levels in drug-naive OCD patients are lower than those in healthy people, but are not lower than those in drug-treated OCD patients. J Affect Disord 2011;133:305310.CrossRefGoogle Scholar
13. Maina, G, Rosso, G, Zanardini, R et al. Serum levels of brain-derived neurotrophic factor in drug-naive obsessive-compulsive patients: a case-control study. J Affect Disord 2010;122:174178.CrossRefGoogle ScholarPubMed
14. Egan, MF, Kojima, M, Callicott, JH et al. The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell 2003;112:257269.CrossRefGoogle ScholarPubMed
15. Chen, ZY, Patel, PD, Sant, G et al. Variant brain-derived neurotrophic factor (BDNF) (Met66) alters the intracellular trafficking and activity-dependent secretion of wild-type BDNF in neurosecretory cells and cortical neurons. J Neurosci 2004;24:44014411.CrossRefGoogle ScholarPubMed
16. Gratacos, M, Gonzalez, JR, Mercader, JM, de Cid, R, Urretavizcaya, M, Estivill, X. Brain-derived neurotrophic factor Val66Met and psychiatric disorders: meta-analysis of case-control studies confirm association to substance-related disorders, eating disorders, and schizophrenia. Biol Psychiatry 2007;61:911922.CrossRefGoogle Scholar
17. Mossner, R, Walitza, S, Lesch, KP et al. Brain-derived neurotrophic factor V66M polymorphism in childhood-onset obsessive-compulsive disorder. Int J Neuropsychopharmacol 2005;8:133136.CrossRefGoogle ScholarPubMed
18. Alonso, P, Gratacos, M, Menchon, JM et al. Extensive genotyping of the BDNF and NTRK2 genes define protective haplotypes against obsessive-compulsive disorder. Biol Psychiatry 2008;63:619628.CrossRefGoogle ScholarPubMed
19. Zai, G, Arnold, P, Strauss, J et al. No association between brain-derived neurotrophic factor gene and obsessive-compulsive disorder. Psychiatr Genet 2005;15:235.CrossRefGoogle Scholar
20. Hall, D, Dhilla, A, Charalambous, A, Gogos, JA, Karayiorgou, M. Sequence variants of the brain-derived neurotrophic factor (BDNF) gene are strongly associated with obsessive-compulsive disorder. Am J Hum Genet 2003;73:370376.CrossRefGoogle ScholarPubMed
21. Wendland, JR, Kruse, MR, Cromer, KR, Murphy, DL. A large case-control study of common functional SLC6A4 and BDNF variants in obsessive-compulsive disorder. Neuropsychopharmacology 2007;32:25432551.CrossRefGoogle Scholar
22. Marquez, L, Camarena, B, Hernandez, S, Loyzaga, C, Vargas, L, Nicolini, H. Association study between BDNF gene variants and Mexican patients with obsessive-compulsive disorder. Eur Neuropsychopharmacol 2013;23:16001605.CrossRefGoogle ScholarPubMed
23. Hemmings, SM, Lochner, C, van der Merwe, L, Cath, DC, Seedat, S, Stein, DJ. BDNF Val66Met modifies the risk of childhood trauma on obsessive-compulsive disorder. J Psychiatr Res 2013;47:18571863.CrossRefGoogle ScholarPubMed
24. Tükel, R, Gurvit, H, Ozata, B et al. Brain-derived neurotrophic factor gene Val66Met polymorphism and cognitive function in obsessive-compulsive disorder. Am J Med Genet B Neuropsychiatr Genet 2012;159B:850858.CrossRefGoogle ScholarPubMed
25. da Rocha, FF, Malloy-Diniz, L, Lage, NV, Correa, H. Positive association between MET allele (BDNF Val66Met polymorphism) and obsessive-compulsive disorder. Rev Bras Psiquiatr 2010;32:323324.CrossRefGoogle Scholar
26. Katerberg, H, Lochner, C, Cath, DC et al. The role of the brain-derived neurotrophic factor (BDNF) val66met variant in the phenotypic expression of obsessive-compulsive disorder (OCD). Am J Med Genet B Neuropsychiatr Genet 2009;150B:10501062.CrossRefGoogle Scholar
27. Wang, Y, Xiao, ZP, Yu, SY, Li, Y, Wang, DX. Association study of brain-derived neurotrophic factor and generalized anxiety disorder and obsessive compulsive disorder. Chin J Nerv Ment Dis 2009;35:623625. (in Chinese).Google Scholar
28. Liu, YH, Liu, SG, Kou, HY, Zhang, XH. Association study of brain-derived neurotrophic factor (BDNF) genetic polymorphism and obsessive-compulsive disorder. J Clin Psychiatry 2013;23:2931. (in Chinese).Google Scholar
29. Hemmings, SM, Kinnear, CJ, Van der Merwe, L et al. Investigating the role of the brain-derived neurotrophic factor (BDNF) val66met variant in obsessive-compulsive disorder (OCD). World J Biol Psychiatry 2008;9:126134.CrossRefGoogle Scholar
30. Munafo, MR, Flint, J. Meta-analysis of genetic association studies. Trends Genet 2004;20:439444.CrossRefGoogle Scholar
31. Wells, GA, Shea, B, O’Connell, D et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Retrieved 3 January 2015 from http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp Google Scholar
32. Higgins, JP, Thompson, SG. Quantifying heterogeneity in a meta-analysis. Stat Med 2002;21:15391558.CrossRefGoogle ScholarPubMed
33. Zai, G. Genetic study of the brain-derived neurotrophic factor (BDNF) gene in obsessive-compulsive disorder (OCD). Biol Psychiatry 2009;65:86S.Google Scholar
34. Shimizu, E, Hashimoto, K, Iyo, M. Ethnic difference of the BDNF 196G/A (val66met) polymorphism frequencies: the possibility to explain ethnic mental traits. Am J Med Genet B Neuropsychiatr Genet 2004;126B:122123.CrossRefGoogle ScholarPubMed
35. Petryshen, TL, Sabeti, PC, Aldinger, KA et al. Population genetic study of the brain-derived neurotrophic factor (BDNF) gene. Mol Psychiatry 2010;15:810815.CrossRefGoogle ScholarPubMed
36. Taylor, S. Molecular genetics of obsessive-compulsive disorder: a comprehensive meta-analysis of genetic association studies. Mol Psychiatry 2013;18:799805.CrossRefGoogle ScholarPubMed
37. Pauls, DL. The genetics of obsessive-compulsive disorder: a review. Dialogues Clin Neurosci 2010;12:149163.Google ScholarPubMed
38. Pauls, DL, Abramovitch, A, Rauch, SL, Geller, DA. Obsessive-compulsive disorder: an integrative genetic and neurobiological perspective. Nat Rev Neurosci 2014;15:410424.CrossRefGoogle ScholarPubMed
39. da Rocha, FF, Malloy-Diniz, L, Lage, NV, Correa, H. The relationship between the Met allele of the BDNF Val66Met polymorphism and impairments in decision making under ambiguity in patients with obsessive-compulsive disorder. Genes Brain Behav 2011;10:523529.CrossRefGoogle ScholarPubMed
40. Alonso, P, Lopez-Sola, C, Gratacos, M et al. The interaction between Comt and Bdnf variants influences obsessive-compulsive-related dysfunctional beliefs. J Anxiety Disord 2013;27:321327.CrossRefGoogle ScholarPubMed
41. Fullana, MA, Alonso, P, Gratacos, M et al. Variation in the BDNF Val66Met polymorphism and response to cognitive-behavior therapy in obsessive-compulsive disorder. Eur Psychiatry 2012;27:386390.CrossRefGoogle ScholarPubMed
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