Brain-derived neurotrophic factor levels and its Val66Met gene polymorphism predict tardive dyskinesia treatment response to Ginkgo biloba.
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.
Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, Texas, USA. xyzhang@bcm.edu
Xiang Yang
XY
Zhang
Wu-Fang
WF
Zhang
Dong-Feng
DF
Zhou
Da Chun
DC
Chen
Mei Hong
MH
Xiu
Hao-Ran
HR
Wu
Colin N
CN
Haile
Therese A
TA
Kosten
Thomas R
TR
Kosten
D000328:Adult; D000704:Analysis of Variance; D014150:Antipsychotic Agents / Q000009:adverse effects; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood* / Q000235:genetics*; D002681:China; D005260:Female; D005838:Genotype; D020441:Ginkgo biloba; D006801:Humans; D008297:Male; D008715:Methionine / Q000235:genetics*; D008875:Middle Aged; D009069:Movement Disorders / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics*; D010597:Pharmacogenetics; D010936:Plant Extracts / Q000627:therapeutic use*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011237:Predictive Value of Tests; D012044:Regression Analysis; D012559:Schizophrenia / Q000188:drug therapy; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014633:Valine / Q000235:genetics*; D000096983:Ginkgo Extract
D014150:Antipsychotic Agents; D019208:Brain-Derived Neurotrophic Factor; D008715:Methionine; D010936:Plant Extracts; D014633:Valine; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract