Background
Tardive dyskinesia (TD) has no well-accepted treatments or known pathophysiology,
but low brain-derived neurotrophic factor (BDNF) may play an important role in its
pathophysiology. Ginkgo biloba (EGb-761) is a potent antioxidant that has neuroprotective effects mediated through
enhancing BDNF levels. We hypothesized that treatment with EGb-761 would increase
serum BDNF levels and reduce TD, particularly among schizophrenia patients who have
the BDNF valine 66 to methionine (Val66Met) genotype (Val/Val).
Methods
Serum BDNF levels and genotyping for the BDNF gene Val66Met polymorphism were assessed
in Chinese schizophrenic patients with (n = 368) and without (n = 563) TD as well as healthy control subjects (n = 546). About half of the TD patients (n = 157) then participated in a double-blind, randomized, placebo-control 12-week treatment
with 240 mg per day of EGb-761. Serum BDNF levels were measured again at posttreatment.
Clinical efficacy was determined using the Abnormal Involuntary Movement Scale (AIMS).
Results
TD patients had lower BDNF levels than the non-TD patients and healthy controls. EGb-761
treatment improved symptoms of TD and increased BDNF levels compared with placebo
treatment. Moreover, the improvement of AIMS total score correlated with the increase
in BDNF levels. Furthermore, improvement in the AIMS score was greatest in those with
the Val/Val allele and lowest with the Met/Met allele.
Conclusions
The BDNF system may be implicated in the pathophysiology of TD and its improvement
with antioxidant treatment. Furthermore, patients with the genetic potential for greater
BDNF release (Val/Val at 66) may obtain a greater reduction in TD from EGb-761 treatment.
Key Words
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References
- Tardive dyskinesia and new antipsychotics.Curr Opin Psychiatry. 2008; 21: 151-156
- Tardive dyskinesia: Eliminated, forgotten, or overshadowed?.Curr Opin Psychiatry. 2007; 20: 131-137
- Oxidative mechanisms and tardive dyskinesia.CNS Drugs. 2003; 17: 47-62
- Oxygen radicals and neuropsychiatric illness.Arch Gen Psychiatry. 1991; 48: 1097-1106
- Free radical involvement in neuropsychiatric illnesses.Psychopharmacol Bull. 1995; 31: 159-165
- Anterograde transport of brain-derived neurotrophic factor and its role in the brain.Nature. 1997; 389: 856-886
- Medial nigral dopamine neurons have rich neurotrophin support in humans.Neuroreport. 1998; 9: 2847-2851
- NT-3 and BDNF protect CNS neurons against metabolic/excitotoxic insults.Brain Res. 1994; 640: 56-67
- Markers for glutamatergic neurotransmission and oxidative stress associated with tardive dyskinesia.Am J Psychiatry. 1998; 155: 1207-1213
- Decreased plasma brain-derived neurotrophic factor levels in schizophrenic patients with tardive dyskinesia: Association with dyskinetic movements.Schizophr Res. 2005; 74 (263–227)
- The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function.Cell. 2003; 112: 257-269
- No association between the brain-derived neurotrophic factor gene Val66Met polymorphism and tardive dyskinesia in schizophrenic patients.Prog Neuropsychopharmacol Biol Psychiatry. 2008; 32: 1545-1548
- Genetic study of BDNF, DRD3, and their interaction in tardive dyskinesia.Eur Neuropsychopharmacol. 2009; 19: 317-328
- Ginkgo biloba: A living fossil.Am J Med. 2000; 108: 341-342
- In vivo studies with EGb 761.in: Defeudis F.V. Ginkgo Biloba Extract (EGb): Pharmacological Activities and Clinical Applications. Elsevier, Paris1991: 61-66
- The CNS effects of Ginkgo biloba extracts and ginkgolide B.Prog Neurobiol. 2002; 67: 235-257
- Oxidative stress, antioxidants and neurodegenerative diseases.Curr Pharm Des. 2005; 11: 2033-2052
- The in vivo neuromodulatory effects of the herbal medicine ginkgo biloba.Proc Natl Acad Sci U S A. 2001; 98: 6577-6658
- The Ginkgo biloba extract EGb 761 rescues the PC12 neuronal cells from beta-amyloid-induced cell death by inhibiting the formation of beta-amyloid-derived diffusible neurotoxic ligands.Brain Res. 2001; 889: 181-190
- Bilobalide and neuroprotection.Pharmacol Res. 2002; 46: 565-568
- Inhibition of amyloid-beta aggregation and caspase-3 activation by the Ginkgo biloba extract EGb761.Proc Natl Acad Sci U S A. 2002; 99 (12197–1202)
- EGb 761 enhances adult hippocampal neurogenesis and phosphorylation of CREB in transgenic mouse model of Alzheimer's disease.FASEB J. 2007; 21: 2400-2408
- Stimulation of neurogenesis and synaptogenesis by bilobalide and quercetin via common final pathway in hippocampal neurons.J Alzheimers Dis. 2009; 18: 787-798
- Extract of ginkgo biloba treatment for tardive dyskinesia in schizophrenia: A randomized, double-blind, placebo-controlled trial.J Clin Psychiatry. 2011; 72: 615-621
- Structured Clinical Interview for DSM-IV Axis I Disorders-Patient Edition (SCID I/P, version 2.0).New York State Psychiatric Institute, Biometrics Research Department, New York1995
- Research diagnoses for tardive dyskinesia.Arch Gen Psychiatry. 1982; 39: 486-487
- Introduction.in: Ginkgo Biloba Extract (EGb761): Pharmacological Activities and Clinical Applications. Elsevier, Paris, France1991: 1-7
- Decreased serum BDNF levels in chronic institutionalized schizophrenia on long-term treatment with typical and atypical antipsychotics.Prog Neuropsychopharmacol Biol Psychiatry. 2009; 33: 1508-1512
- The brain derived neurotrophic factor gene confers susceptibility to bipolar disorder: Evidence from a family-based association study.Am J Hum Genet. 2002; 71: 651-655
- BDNF levels and genotype are associated with antipsychotic-induced weight gain in patients with chronic schizophrenia.Neuropsychopharmacology. 2008; 33: 2200-2205
- Chlorpromazine equivalent doses for the newer atypical antipsychotics.J Clin Psychiatry. 2003; 64: 663-667
- Melatonin treatment for tardive dyskinesia: A double-blind, placebo-controlled, crossover study.Arch Gen Psychiatry. 2001; 58: 1049-1052
- Treatment of tardive dyskinesia with galantamine: A randomized controlled crossover trial.J Clin Psychiatry. 2007; 68: 410-415
- Brain-derived neurotrophic factor protects against ischemic cell damage in rat hippocampus.J Cereb Blood Flow Metab. 1994; 14: 689-692
- Possible involvement of free radicals in neuroleptic-induced movement disorders.Ann N Y Acad Sci. 1989; 570: 176-185
- A double-blind, placebo-controlled, randomized trial of Ginkgo biloba extract EGb 761 in a sample of cognitively intact older adults: Neuropsychological findings.Hum Psychopharmacol. 2002; 17: 267-277
- Ginkgo biloba and donepezil: A comparison in the treatment of Alzheimer's dementia in a randomized placebo-controlled double-blind study.Eur J Neurol. 2006; 13: 981-985
- Ginkgo biloba extract EGb 761(R), donepezil or both combined in the treatment of Alzheimer's disease with neuropsychiatric features: A randomised, double-blind, exploratory trial.Aging Ment Health. 2009; 13: 183-190
- Restoration of impaired phosphorylation of cyclic AMP response element-binding protein (CREB) by EGb 761 and its constituents in Abeta-expressing neuroblastoma cells.Eur J Neurosci. 2007; 26: 2931-2939
- Effects of ginkgolide on the development of NOS and AChE positive neurons in the embryonic basal forebrain.Cell Biol Int. 2006; 30: 500-504
- The effect of extract of ginkgo biloba added to haloperidol on superoxide dismutase in inpatients with chronic schizophrenia.J Clin Psychopharmacol. 2001; 21: 85-88
- A double-blind, placebo-controlled trial of extract of Ginkgo biloba added to haloperidol in treatment-resistant patients with schizophrenia.J Clin Psychiatry. 2001; 62: 878-883
- Variant brain-derived neurotrophic factor (BDNF) (Met66) alters the intracellular trafficking and activity-dependent secretion of wild-type BDNF in neurosecretory cells and cortical neurons.J Neurosci. 2004; 24: 4401-4411
Article info
Publication history
Published online: June 14, 2012
Accepted:
April 26,
2012
Received in revised form:
April 25,
2012
Received:
January 24,
2012
Footnotes
Authors XYZ, W-FZ, and D-FZ contributed equally to this work.
Identification
Copyright
© 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
