The Role of the Brain-Derived Neurotrophic Factor (BDNF) val66met Variant in the Phenotypic Expression of Obsessive-Compulsive Disorder (OCD)

被引:66
作者
Katerberg, Hilga [1 ,2 ]
Lochner, Christine [3 ]
Cath, Danielle C. [4 ,5 ]
de Jonge, Peter [1 ,6 ]
Bochdanovits, Zoltan [2 ,7 ]
Moolman-Smook, Johanna C. [8 ]
Hemmings, Sian M. J. [8 ]
Carey, Paul D. [3 ]
Stein, Dan J. [3 ,9 ]
Sondervan, David [2 ]
den Boer, Johan A. [1 ]
van Balkom, Anton J. L. M. [4 ,5 ]
Polman, Annemiek [1 ]
Heutink, Peter [2 ,7 ]
机构
[1] Univ Groningen, Dept Psychiat, Univ Med Ctr Groningen, NL-9700 RB Groningen, Netherlands
[2] Vrije Univ Amsterdam Med Ctr, Sect Med Genom, Dept Clin Genet, Amsterdam, Netherlands
[3] Univ Stellenbosch, Dept Psychiat, MRC Unit Anxiety & Stress Disorders, ZA-7600 Stellenbosch, South Africa
[4] Vrije Univ Amsterdam Med Ctr, Dept Psychiat, Amsterdam, Netherlands
[5] GGZ Buitenamstel, Amsterdam, Netherlands
[6] Univ Groningen, Dept Internal Med, Univ Med Ctr Groningen, NL-9700 RB Groningen, Netherlands
[7] Vrije Univ Amsterdam, CNCR, Amsterdam, Netherlands
[8] Univ Stellenbosch, MRC US Ctr Mol & Cellular Biol, ZA-7600 Stellenbosch, South Africa
[9] Univ Cape Town, Dept Psychiat, ZA-7925 Cape Town, South Africa
关键词
obsessive-compulsive disorder; item-level factor analysis; symptom dimensions; age of onset; Yale-Brown obsessive compulsive scale severity; SEROTONIN TRANSPORTER FUNCTION; AFFECTED SIBLING PAIRS; SYMPTOM DIMENSIONS; ANXIETY BEHAVIOR; EARLY-ONSET; ASSOCIATION; GENE; POLYMORPHISM; 5-HTTLPR; GENDER;
D O I
10.1002/ajmg.b.30930
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Evidence suggests that the Va166Met variant of the brain-derived neurotrophic factor (BDNF) gene may play a role in the etiology of Obsessive-Compulsive Disorder (OCD). In this study, the role of the BDNF Va166Met variant in the etiology and the phenotypic expression of OCD is investigated. Associations between the BDNF Va166Met variant and OCD, obsessive-compulsive symptom dimensions, Yale-Brown Obsessive Compulsive Scale (YBOCS) severity scores, age of onset and family history of obsessive-compulsive symptoms were assessed. The BDNF Va166Met variant was genotyped in 419 patients with sub-/ clinical OCD and 650 controls. No differences in allele or genotype frequency were observed between cases and controls. In females with OCD, the Met66Met genotype was associated with later age of onset and a trend for a negative family history, whereas the Val66Val genotype was associated with a trend for lower YBOCS severity scores. Item-level factor analysis revealed six factors: 1) Contamination/cleaning; 2) Aggressive obsessions/checking; 3) Symmetry obsessions, counting, ordering and repeating; 4) Sexual/religious obsessions; 5) Hoarding and 6) Somatic obsessions/checking. A trend was found for a positive association between Factor 4 (Sexual/religious obsessions) and the BDNF Val66Val genotype. The results suggest that BDNF function may be implicated in the mediation of OCD. We found that for the BDNF Met66Met genotype may be associated with a milder phenotype in females and a possible role for the BDNF Val66Val genotype and the BDNF Val66 allele in the sexual/religious obsessions. (C) 2009 Wiley-Liss, Inc.
引用
收藏
页码:1050 / 1062
页数:13
相关论文
共 65 条
  • [1] Extensive genotyping of the BDNF and NTRK2 genes define protective haplotypes against obsessive-compulsive disorder
    Alonso, Pino
    Gratacos, Monica
    Menchon, Jose M.
    Saiz-Ruiz, Jeronimo
    Segalas, Cinto
    Baca-Garcia, Enrique
    Labad, Javier
    Fernandez-Piqueras, Jose
    Real, Eva
    Vaquero, Concepcion
    Perez, Mercedes
    Dolengevich, Helen
    Gonzalez, Juan R.
    Bayes, Monica
    de Cid, Rafael
    Vallejo, Julio
    Estivill, Xavier
    [J]. BIOLOGICAL PSYCHIATRY, 2008, 63 (06) : 619 - 628
  • [2] Alsobrook JP, 1999, AM J MED GENET, V88, P669, DOI 10.1002/(SICI)1096-8628(19991215)88:6<669::AID-AJMG17>3.0.CO
  • [3] 2-N
  • [4] American Psychiatric Association, 2013, Diagnostic and statistical manual of mental disorders: DSM-5, V5th ed., DOI DOI 10.1176/APPI.BOOKS.9780890425596
  • [5] Obsessive-compulsive severity spectrum in the community:: prevalence, comorbidity, and course
    Angst, J
    Gamma, A
    Endrass, J
    Goodwin, R
    Ajdacic, V
    Eich, D
    Rössler, W
    [J]. EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE, 2004, 254 (03) : 156 - 164
  • [6] Browne M.W., 1993, Sociological Methods and Research, P136, DOI DOI 10.1177/0049124192021002005
  • [7] Role of the brain-derived neurotrophic factor at glutamatergic synapses
    Carvalho, A. L.
    Caldeira, M. V.
    Santos, S. D.
    Duarte, C. B.
    [J]. BRITISH JOURNAL OF PHARMACOLOGY, 2008, 153 : S310 - S324
  • [8] Exploratory factor analysis of obsessive-compulsive patients and association with 5-HTTLPR polymorphism
    Cavallini, MC
    Di Bella, D
    Siliprandi, F
    Malchiodi, F
    Bellodi, L
    [J]. AMERICAN JOURNAL OF MEDICAL GENETICS, 2002, 114 (03): : 347 - 353
  • [9] Genetic variant BDNF (Val66Met) polymorphism alters anxiety-related behavior
    Chen, Zhe-Yu
    Jing, Deqiang
    Bath, Kevin G.
    Ieraci, Alessandro
    Khan, Tanvir
    Siao, Chia-Jen
    Herrera, Daniel G.
    Toth, Miklos
    Yang, Chingwen
    McEwen, Bruce S.
    Hempstead, Barbara L.
    Lee, Francis S.
    [J]. SCIENCE, 2006, 314 (5796) : 140 - 143
  • [10] Serotonin transporter function, but not expression, is dependent on brain-derived neurotrophic factor (BDNF):: in vivo studies in BDNF-deficient mice
    Daws, L. C.
    Munn, J. L.
    Valdez, M. F.
    Frosto-Burke, T.
    Hensler, J. G.
    [J]. JOURNAL OF NEUROCHEMISTRY, 2007, 101 (03) : 641 - 651