Title:Ginkgo biloba for Tardive Dyskinesia and Plasma MnSOD Activity: Association with MnSOD Ala-9Val Variant: A Randomized, Double-blind Trial
Volume: 22
Issue: 14
Author(s): Dongmei Wang, Yang Tian, Jiajing Chen, Rongrong Zhu, Jiaxin Li, Huixia Zhou, Dachun Chen, Li Wang, Thomas R. Kosten and Xiang-Yang Zhang*
Affiliation:
- CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China
- Department of Psychology, University of Chinese Academy of Sciences, Beijing, China
Keywords:
Schizophrenia, genotype, pharmacogenetics, ginkgo biloba extract, tardive dyskinesia, plasma MnSOD.
Abstract:
Background: Excessive free radicals are implicated in the pathophysiology of tardive dyskinesia
(TD), and Ginkgo biloba extract (EGb761) scavenges free radicals, thereby enhancing antioxidant
enzymes such as mitochondrial manganese superoxide dismutase (MnSOD). This study examined
whether EGb761 treatment would improve TD symptoms and increase MnSOD activity, particularly
in TD patients with specific MnSOD Val-9Ala genotype.
Methods: An EGb761 (240 mg/day) 12-week double-blind clinical trial with 157 TD patients was
randomized. The severity of TD was measured by the Abnormal Involuntary Movement Scale (AIMS)
and plasma MnSOD activity was assayed before and after 12 weeks of treatment. Further, in an expanded
sample, we compared MnSOD activity in 159 TD, 227 non-TD and 280 healthy controls, as
well as the allele frequencies and genotypes for the MnSOD Ala-9Val polymorphism in 352 TD, 486
non-TD and 1150 healthy controls.
Results: EGb761 significantly reduced TD symptoms and increased MnSOD activity in TD patients
compared to placebo (both p < 0.01). Moreover, we found an interaction between genotype and treatment
response (p < 0.001). Furthermore, in the EGb761 group, patients carrying the Ala allele displayed a significantly
lower AIMS total score than patients with the Val/Val genotype. In addition, MnSOD activity
was significantly lower at baseline in TD patients compared with healthy controls or non-TD patients.
Conclusion: EGb761 treatment enhanced low MnSOD activity in TD patients and produced greater
improvement in TD symptoms in patients with the Ala allele of the MnSOD Ala-9Val polymorphism.
