Brain Derived Neurotrophic Factor (BDNF) gene variants association with age at onset and therapeutic response in schizophrenia

被引:142
作者
Krebs, MO
Guillin, O
Bourdel, MC
Schwartz, JC
Olie, JP
Poirier, MF
Sokoloff, P
机构
[1] Univ Paris 05, Hop St Anne, Dept Mental Hlth & Therapeut, Biol Psychiat Lab,UPRES EA 2501,Serv Hosp Univ, F-75014 Paris, France
[2] INSERM, U109, Dept Neurobiol & Mol Pharmacol, Paris, France
关键词
association study; neurodevelopment; drug abuse; dopamine D3 receptor; neurotrophin;
D O I
10.1038/sj.mp.4000749
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Schizophrenia is a heterogeneous disease involving genetic and environmental factors. The frequency of structural brain abnormalities(1,2) or physical anomalies(3) supports a neurodevelopmental etiology, especially in early onset schizophrenia.(4) Brain-Derived-Neurotrophic-Factor (BDNF) is involved in the neurodevelopment of dopaminergic (DA)-related systems(5,6) and interacts with the meso-limbic DA systems,(7-10) involved in the therapeutic response to antipsychotic drugs(11) and substance abuse.(12) In addition, BDNF promotes and maintains dopamine D3 receptor (DRD3) expression.(13) In a French Caucasian population, we found no statistical difference in allele or genotype distribution of the BDNF gene dinucleotide repeat polymorphism (166-174 bp)(14) between the whole group of schizophrenic patients and controls. By contrast, an excess of the 172-176 bp alleles was found in patients with late onset, in neuroleptic-responding patients and in non-substance-abusing patients. BDNF gene variants thus appear to be associated with developmental features of schizophrenia. In addition, this association with good treatment responding was independent from the association found with the DRD3 Ban gene polymorphism in the same population.(15) These results suggest an independent contribution of each gene to a treatment-sensitive form of schizophrenia.
引用
收藏
页码:558 / 562
页数:5
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