期刊
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
卷 39, 期 1, 页码 96-101出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pnpbp.2012.05.014
关键词
Antipsychotic response; Antipsychotic-induced weight gain; Brain-derived neurotrophic factor (BDNF); Pharmacogenetics; Schizophrenia
资金
- CIHR operating grant [MOP 115097, MOP 89853]
- NARSAD Young Investigator Award
- OMHF New Investigator Fellowship
- American Foundation for Suicide Prevention
- Eli Lilly
- Canadian Institutes of Health Research
- Ontario Mental Health Foundation
- Abbott Labs
- ACADIA
- Bristol Myers Squibb
- Janssen
- Pfizer
- Astra Zeneca
- GlaxoSmithKline
- Memory
- Cephalon
- Minster
- Aryx
- BiolineRx
- Bristol-Myers Squibb
- Forest Labs
- Novartis
- Solvay
- Bioline
- Dainippon Sumitomo
- Elan
- Forest Laboratories
- Fujisawa
- Janssen Pharmaceutica
- Merck
- Ono
- Organon
- Otsuka
- Solvay Pharmaceuticals
- Roche
- NIH
- Harvard Massachusetts General Hospital
- Brigham and Women's Hospital
- Vanda
- Wyeth
Background: Brain-derived neurotrophic factor (BDNF) has extensive effects on the nervous system including cell survival, differentiation, neuronal growth and maintenance, as well as cell death. Moreover, it promotes synaptic plasticity and interacts with dopaminergic and serotonergic neurons, suggesting an important role on the alteration of brain function with antipsychotic medications and induced weight gain in schizophrenia patients. The differential effects of BDNF gene variants could lead to changes in brain circuitry that would in turn cause variable response to antipsychotic medication. Therefore, we hypothesized that genetic variation in this candidate gene helps in explaining the inter-individual variation observed in antipsychotic drug treatment with respect to response and induced weight gain. Method: We examined four single-nucleotide polymorphisms across the BDNF gene, including Va166Met (rs6265). Prospective BPRS change scores and weight change after six weeks were obtained from a total of 257 schizophrenia patients of European ancestry. Results: The markers rs11030104 and Va166Met were associated with antipsychotic response (P = 0.04; 0.007, respectively). On the other hand, marker rs1519480 was associated with weight gain (P = 0.04). Moreover, a two-marker haplotype across rs6265 and rs1519480 was associated with weight change (P = 0.001). Results with Va166Met in response, and results with rs6265-rs1519480 haplotypes remained significant at the modified Bonferroni corrected alpha of 0.017. Conclusion: BDNF genetic variants might play an important role in predicting antipsychotic response and antipsychotic-induced weight gain. However, replication in larger and independent samples is required. (c) 2012 Elsevier Inc. All rights reserved.
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