Brain-Derived Neurotrophic Factor Levels and Its Val66Met Gene Polymorphism Predict Tardive Dyskinesia Treatment Response to Ginkgo Biloba

Zhang, Xiang Yang; Zhang, Wufang; Zeng, Dongfeng; Chen, Da Chun; Xiu, Mei Hong; Wu, Haoran; Haile, Colin N.; Kosten, Therese A.; Kosten, Thomas R.

doi:10.1016/j.biopsych.2012.04.032

Cited by 48 publications

(28 citation statements)

References 40 publications

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“…Interestingly, our results of a significant relationship between the non-Met genotype in the BDNF Val66Met polymorphism and TD severity are consistent with findings from a recent study reporting that the improvement of AIMS total scores during randomized placebo-controlled treatment with Ginkgo biloba correlated significantly with increases in serum BDNF levels, and that the improvement was greatest in patients with the Val/Val genotype and lowest with the Met/Met genotype (Zhang et al, 2012). However, this study included only Asian subjects with schizophrenia, which does not allow for a simple comparison with the results in Caucasian populations in our meta-analysis.…”

Section: Discussionsupporting

confidence: 92%

“…Furthermore, BDNF protects against reductions in striatal dopamine content by neurotoxins (Hung and Lee, 1996; Angelucci et al, 2005). Notably, several studies found that schizophrenia patients with TD had lower plasma BDNF levels than those without TD (Tan et al, 2005; Yang et al, 2011; Zhang et al, 2012), although Lee et al (2007) showed no differences between the two groups.…”

Section: Introductionmentioning

confidence: 99%

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BDNF Val66Met polymorphism and antipsychotic-induced tardive dyskinesia occurrence and severity: A meta-analysis

Miura

Zhang

Nitta

et al. 2014

Schizophrenia Research

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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 ± 10.4 years; 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.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

BDNF Val66Met polymorphism and antipsychotic-induced tardive dyskinesia occurrence and severity: A meta-analysis

Miura

Zhang

Nitta

et al. 2014

Schizophrenia Research

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“…Can the responsiveness to medications in TD be predicted by studies of genetic polymorphisms known to influence the risk and severity of TD [10]? For instance, in the EGb-761 trial there was greater improvement in the AIMS score in those with the valine/ valine allele of the brain-derived neurotrophic factor gene and less improvement with the methionine/methionine allele [115]. This significant effort requires collaboration between basic, translational, and clinical scientists across the disciplines of psychiatry and neurology.…”

Section: Resultsmentioning

confidence: 99%

Tardive Dyskinesia: Therapeutic Options for an Increasingly Common Disorder

2014

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Tardive dyskinesia (TD) is a serious, often disabling, movement disorder that is caused by medications that block dopamine receptors (i.e., neuroleptics, anti-emetics). There is currently no standard treatment approach for physicians confronted with such patients. This may be the result of notions that TD is disappearing because of the switch to secondgeneration antipsychotic agents and that it is largely reversible.In this article we demonstrate that second-generation antipsychotics do, indeed, cause TD and, in fact, the frequency is likely higher than expected because of growing off-label uses and a tripling of prescriptions written in the last 10 years. In addition, studies demonstrate that TD actually remits in only a minority of patients when these drugs are withdrawn. Furthermore, neuroleptic agents are often utilized to treat TD, despite prolonged exposure being a risk factor for irreversibility. The outcome of these trends is a growing population afflicted with TD. We review non-neuroleptic agents that have shown positive results in small, early-phase, blinded trials, including tetrabenazine, amantadine, levetiracetam, piracetam, clonazepam, propranolol, vitamin B6, and Ginkgo biloba. Other options, such as botulinum toxin and deep brain stimulation, will also be discussed, and a suggested treatment algorithm is provided. While these agents are reasonable treatment options at this time there is a need, with a concerted effort between neurology and psychiatry, for full-scale drug development, including multicenter, randomized, blinded trials to confirm the effectiveness of the agents that were positive in phase 2 trials and the development of newer ones.

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“…It has also been proposed that BDNF levels contribute to TD and that certain polymorphisms of BDNF may increase response to treatment for TD using ginkgo biloba, a potent antioxidant with neuroprotective effects mediated through enhancing BDNF levels (114). BDNF is a neuronal growth and survival peptide that modulates a variety of processes including regulation of the dopamine D3 receptor (DRD3) and could thus be involved in TD through this mechanism (75).…”

Section: Pharmacodynamicsmentioning

confidence: 99%

Genetics of antipsychotic drug outcome and implications for the clinician: into the limelight

Changasi

Shams

Pouget

et al. 2014

Translational Developmental Psychiatry

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Background and purpose: Antipsychotics (APs) are the primary method of treatment for schizophrenia and other psychotic disorders. Unfortunately, lengthy trial-and-error approaches are typically required to find the optimal medication and dosage due to a large interindividual variability with outcome to AP treatment. The literature has shown abundant evidence for a genetic component in individuals' responses to APs. Pharmacogenetic studies analyze specific genetic markers and their association with symptom improvement and occurrence of side effects with APs. This research aims to optimize AP drug treatment by usage of predictive testing and to personalize medicine. Recent findings: This review will highlight the most consistent findings in pharmacogenetics of APs and will update the reader on the clinical implications. This will include how genetic variants modulate AP drug levels, side effects, and therapeutic symptom improvement (i.e. response) to AP treatment. Summary: Several promising findings were obtained implicating gene variants of the dopamine receptor genes in addition to gene variants of serotonin receptors for response and common side effects. Notably, effect sizes appear to be particularly high in the genetics of side effects compared to response. One example is antipsychotic-induced weight gain where the leptin, HTR2C and in particular the melanocortin-4-receptor (MC4R) genes have been implicated in weight gain in children and adolescents. Consistent findings were also obtained for genes implicated in tardive dyskinesia and agranulocytosis. However, the most clinically relevant findings pertain to genes involved in drug metabolism such as the CYP2D6 and CYP2C19 genes which have been included in the first genetic test kits such as the Amplichip †

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Brain-Derived Neurotrophic Factor Levels and Its Val66Met Gene Polymorphism Predict Tardive Dyskinesia Treatment Response to Ginkgo Biloba

Cited by 48 publications

References 40 publications

BDNF Val66Met polymorphism and antipsychotic-induced tardive dyskinesia occurrence and severity: A meta-analysis

BDNF Val66Met polymorphism and antipsychotic-induced tardive dyskinesia occurrence and severity: A meta-analysis

Tardive Dyskinesia: Therapeutic Options for an Increasingly Common Disorder

Genetics of antipsychotic drug outcome and implications for the clinician: into the limelight

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