A Brain-Derived Neurotrophic Factor Haplotype Is Associated with Therapeutic Response in Obsessive-Compulsive Disorder

被引:34
作者
Real, Eva [1 ]
Gratacos, Monica [3 ,5 ,6 ]
Soria, Virginia [2 ]
Escaramis, Gerogia [3 ,5 ,6 ]
Alonso, Pino [1 ,2 ,4 ]
Segalas, Cinto [1 ]
Bayes, Monica [5 ,6 ]
de Cid, Rafael [5 ,6 ]
Menchon, Jose M. [1 ,2 ,4 ]
Estivill, Xavier [3 ,5 ,6 ,7 ]
机构
[1] Bellvitge Univ Hosp, Dept Psychiat, OCD Clin & Res Unit, Barcelona 08907, Spain
[2] Bellvitge Univ Hosp, Dept Psychiat, Inst Salud Carlos III, CIBERSAM, Barcelona 08907, Spain
[3] Bellvitge Univ Hosp, Dept Psychiat, Inst Salud Carlos III, CIBERESP, Barcelona 08907, Spain
[4] Univ Barcelona, Dept Clin Sci, Ctr Genom Regulat, Barcelona, Spain
[5] Univ Barcelona, Genes & Dis Program, Barcelona, Spain
[6] Univ Barcelona, CeGen Barcelona Genotyping Node, Barcelona, Spain
[7] Pompeu Fabra Univ, Dept Expt & Hlth Sci, Barcelona, Spain
关键词
Association; BDNF; haplotype; obsessive-compulsive disorder; TagSNP; treatment outcome; SINGLE-NUCLEOTIDE POLYMORPHISMS; FACTOR BDNF; DEPRESSED-PATIENTS; FACTOR GENE; FAMILY; VAL66MET; NEUROBIOLOGY; MILNACIPRAN; INHIBITORS; HISTORY;
D O I
10.1016/j.biopsych.2009.05.017
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Background: Several clinical and genetic studies have focused on the role of brain-derived neurotrophic factor (BDNF) in the pathophysiology of various mental disorders. Recent lines of evidence regarding the network hypothesis of treatment outcome point towards the involvement of BDNF variants in the pharmacologic response in mood disorders (MD). Furthermore, there is strong evidence of a role for the serotonergic system in the pathophysiology and treatment of OCD, and upregulation of BDNF has been observed with various classes of antidepressants, including selective serotonin reuptake inhibitors (SSRI). Thus, we hypothesized that the BDNF gene might also be associated with treatment outcome in OCD. Methods: We performed a single-marker and haplotype association study of eight tag single nucleotide polymorphisms in the BDNF genomic region and related this to pharmacologic response in a sample of 131 OCD patients. Results: We found an association for a haplotype containing two single nucleotide polymorphisms that have previously been reported to be associated with treatment outcome in MID (rs908867 and rs1491850). Conclusions: Our results support the hypothesis that the BDNF gene is involved in the response to psychopharmacologic treatment even though these preliminary findings await replication in a follow-up sample.
引用
收藏
页码:674 / 680
页数:7
相关论文
共 51 条
[1]   Extensive genotyping of the BDNF and NTRK2 genes define protective haplotypes against obsessive-compulsive disorder [J].
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 .
BIOLOGICAL PSYCHIATRY, 2008, 63 (06) :619-628
[2]  
ANDREASEN NC, 1977, ARCH GEN PSYCHIAT, V34, P1229
[3]   Haploview: analysis and visualization of LD and haplotype maps [J].
Barrett, JC ;
Fry, B ;
Maller, J ;
Daly, MJ .
BIOINFORMATICS, 2005, 21 (02) :263-265
[4]   Pharmacogenomics and antidepressant drugs [J].
Binder, EB ;
Holsboer, F .
ANNALS OF MEDICINE, 2006, 38 (02) :82-94
[5]  
CAREY G, 1981, ANXIETY NEW RES CHAN
[6]   Selecting a maximally informative set of single-nucleotide polymorphisms for association analyses using linkage disequilibrium [J].
Carlson, CS ;
Eberle, MA ;
Rieder, MJ ;
Yi, Q ;
Kruglyak, L ;
Nickerson, DA .
AMERICAN JOURNAL OF HUMAN GENETICS, 2004, 74 (01) :106-120
[7]   Genetic variant BDNF (Val66Met) polymorphism alters anxiety-related behavior [J].
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. .
SCIENCE, 2006, 314 (5796) :140-143
[8]   Brain-derived neurotrophic factor gene polymorphism (Val66Met) and citalopram response in major depressive disorder [J].
Choi, Myoung-Jin ;
Kang, Rhee-Hun ;
Lim, Se-Won ;
Oh, Kang-Seob ;
Lee, Min-Soo .
BRAIN RESEARCH, 2006, 1118 :176-182
[9]  
DEVEAUGHGEISS J, 1991, ARCH GEN PSYCHIAT, V48, P730
[10]   Association studies of serotonin system candidate genes in early-onset obsessive-compulsive disorder [J].
Dickel, Diane E. ;
Veenstra-VanderWeele, Jeremy ;
Bivens, Nancy Chiu ;
Wu, Xiaolin ;
Fischer, Daniel J. ;
Van Etten-Lee, Michelle ;
Himle, Joseph A. ;
Leventhal, Bennett L. ;
Cook, Edwin H., Jr. ;
Hanna, Gregory L. .
BIOLOGICAL PSYCHIATRY, 2007, 61 (03) :322-329