Itaru Miura1, Jian-Ping Zhang2, Masahiro Nitta3, Todd Lencz4, John M Kane4, Anil K Malhotra4, Hirooki Yabe5, Christoph U Correll6. 1. The Zucker Hillside Hospital, Psychiatry Research, North Shore - Long Island Jewish Health System, Glen Oaks, NY, USA; Department of Neuropsychiatry, Fukushima Medical University School of Medicine, Fukushima, Japan. 2. The Zucker Hillside Hospital, Psychiatry Research, North Shore - Long Island Jewish Health System, Glen Oaks, NY, USA; Hofstra North Shore LIJ School of Medicine, Hempstead, NY, USA; The Feinstein Institute for Medical Research, Manhasset, NY, USA. 3. The Zucker Hillside Hospital, Psychiatry Research, North Shore - Long Island Jewish Health System, Glen Oaks, NY, USA; Dainippon Sumitomo Pharma Co., Ltd., Tokyo, Japan. 4. The Zucker Hillside Hospital, Psychiatry Research, North Shore - Long Island Jewish Health System, Glen Oaks, NY, USA; Hofstra North Shore LIJ School of Medicine, Hempstead, NY, USA; The Feinstein Institute for Medical Research, Manhasset, NY, USA; Albert Einstein College of Medicine, Bronx, NY, USA. 5. Department of Neuropsychiatry, Fukushima Medical University School of Medicine, Fukushima, Japan. 6. The Zucker Hillside Hospital, Psychiatry Research, North Shore - Long Island Jewish Health System, Glen Oaks, NY, USA; Hofstra North Shore LIJ School of Medicine, Hempstead, NY, USA; The Feinstein Institute for Medical Research, Manhasset, NY, USA; Albert Einstein College of Medicine, Bronx, NY, USA. Electronic address: ccorrell@lij.edu.
Abstract
BACKGROUND: Tardive dyskinesia (TD) is a serious long-term consequence of antipsychotic treatment. Since brain-derived neurotrophic factor (BDNF) has potent neurotrophic activity, genetic alterations in the BDNF gene may affect antipsychotic-induced TD. METHODS: Searching PubMed and Web of Science until 05/31/13, we conducted a systematic review and a meta-analysis of the effects of BDNF Val66Met polymorphism on antipsychotic-induced TD. Pooled odds ratio was calculated to assess the effects of BDNF Val66Met polymorphism on TD occurrence. Additionally, pooled standardized mean differences (Hedges' g) were calculated to assess the effects on Abnormal Involuntary Movement Scale (AIMS) total score. RESULTS: Out of 699 potentially eligible hits, 6 studies (N=1740, mean age=46.0±10.4years; males=73.1%; Asians=80.5%, Caucasians=19.5%; schizophrenia=96.2%) were included in this meta-analysis. Pooling data from all studies, no significant associations were found between BDNF Val66Met polymorphism and TD (p=0.82) or AIMS total scores (p=0.11). However, in studies including only Caucasians (n=339), Met allele carriers had significantly higher AIMS total scores (Hedges' g=0.253, 95% confidence interval=0.030 to 0.476, p=0.026) and non-significantly higher TD occurrence (p=0.127). Conversely, there was no association between BDNF and AIMS scores (p=0.57) or TD (p=0.65) in Asians. CONCLUSION: Although there was no significant association between BDNF Val66Met polymorphism and TD or AIMS scores across all patients, our results suggest that BDNF Val66Met polymorphism affects severity and, possibly, TD development in Caucasians. Since the number of studies and patients was still small, additional data are needed to confirm genotype-racial interactions. Furthermore, BDNF enhancing treatments for TD may require further study, especially in Caucasians.
BACKGROUND:Tardive dyskinesia (TD) is a serious long-term consequence of antipsychotic treatment. Since brain-derived neurotrophic factor (BDNF) has potent neurotrophic activity, genetic alterations in the BDNF gene may affect antipsychotic-induced TD. METHODS: Searching PubMed and Web of Science until 05/31/13, we conducted a systematic review and a meta-analysis of the effects of BDNFVal66Met polymorphism on antipsychotic-induced TD. Pooled odds ratio was calculated to assess the effects of BDNFVal66Met polymorphism on TD occurrence. Additionally, pooled standardized mean differences (Hedges' g) were calculated to assess the effects on Abnormal Involuntary Movement Scale (AIMS) total score. RESULTS: Out of 699 potentially eligible hits, 6 studies (N=1740, mean age=46.0±10.4years; males=73.1%; Asians=80.5%, Caucasians=19.5%; schizophrenia=96.2%) were included in this meta-analysis. Pooling data from all studies, no significant associations were found between BDNFVal66Met polymorphism and TD (p=0.82) or AIMS total scores (p=0.11). However, in studies including only Caucasians (n=339), Met allele carriers had significantly higher AIMS total scores (Hedges' g=0.253, 95% confidence interval=0.030 to 0.476, p=0.026) and non-significantly higher TD occurrence (p=0.127). Conversely, there was no association between BDNF and AIMS scores (p=0.57) or TD (p=0.65) in Asians. CONCLUSION: Although there was no significant association between BDNFVal66Met polymorphism and TD or AIMS scores across all patients, our results suggest that BDNFVal66Met polymorphism affects severity and, possibly, TD development in Caucasians. Since the number of studies and patients was still small, additional data are needed to confirm genotype-racial interactions. Furthermore, BDNF enhancing treatments for TD may require further study, especially in Caucasians.
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