Ginkgo biloba for Tardive Dyskinesia and Plasma MnSOD Activity: Association with MnSOD Ala-9Val Variant: A Randomized, Double-blind Trial


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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.

About the authors

Dongmei Wang

CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences

Email: info@benthamscience.net

Yang Tian

CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences

Email: info@benthamscience.net

Jiajing Chen

CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences

Email: info@benthamscience.net

Rongrong Zhu

CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences

Email: info@benthamscience.net

Jiaxin Li

CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences

Email: info@benthamscience.net

Huixia Zhou

CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences

Email: info@benthamscience.net

Dachun Chen

, Beijing HuiLongGuan Hospital

Email: info@benthamscience.net

Li Wang

CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences

Email: info@benthamscience.net

Thomas Kosten

Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine

Email: info@benthamscience.net

Xiang-Yang Zhang

CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences

Author for correspondence.
Email: info@benthamscience.net

References

  1. Carbon, M.; Kane, J.M.; Leucht, S.; Correll, C.U. Tardive dyskinesia risk with first‐ and second‐generation antipsychotics in comparative randomized controlled trials: A meta‐analysis. World Psychiatry, 2018, 17(3), 330-340. doi: 10.1002/wps.20579 PMID: 30192088
  2. Lohr, J.B.; Kuczenski, R.; Niculescu, A.B. Oxidative mechanisms and tardive dyskinesia. CNS Drugs, 2003, 17(1), 47-62. doi: 10.2165/00023210-200317010-00004 PMID: 12467492
  3. Cho, C.H.; Lee, H.J. Oxidative stress and tardive dyskinesia: Pharmacogenetic evidence. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2013, 46, 207-213. doi: 10.1016/j.pnpbp.2012.10.018 PMID: 23123399
  4. Bishnoi, M.; Boparai, R.K. An animal model to study the molecular basis of tardive dyskinesia. Methods Mol. Biol., 2012, 829, 193-201. doi: 10.1007/978-1-61779-458-2_12 PMID: 22231815
  5. Zhang, X.Y.; Chen, D.C.; Xiu, M.H.; Yang, F.D.; Tan, Y.; Luo, X.; Zuo, L.; Kosten, T.A.; Kosten, T.R. Cognitive function, plasma MnSOD activity, and MnSOD Ala-9Val polymorphism in patients with schizophrenia and normal controls. Schizophr. Bull., 2014, 40(3), 592-601. doi: 10.1093/schbul/sbt045 PMID: 23588476
  6. Zhang, X.Y.; Tan, Y.L.; Zhou, D.F.; Cao, L.Y.; Wu, G.Y.; Haile, C.N.; Kosten, T.A.; Kosten, T.R. Disrupted antioxidant enzyme activity and elevated lipid peroxidation products in schizophrenic patients with tardive dyskinesia. J. Clin. Psychiatry, 2007, 68(5), 754-760. doi: 10.4088/JCP.v68n0513 PMID: 17503985
  7. Factor, S.A. Management of Tardive Syndrome: Medications and surgical treatments. Neurotherapeutics, 2020, 17(4), 1694-1712. doi: 10.1007/s13311-020-00898-3 PMID: 32720245
  8. Soares-Weiser, K.; Maayan, N.; Bergman, H. Vitamin E for antipsychotic-induced tardive dyskinesia. Cochrane Database Syst. Rev., 2018, 1(1), CD000209. PMID: 29341067
  9. Fedota, J.R.; Matous, A.L.; Salmeron, B.J.; Gu, H.; Ross, T.J.; Stein, E.A. Insula demonstrates a non-linear response to varying demand for cognitive control and weaker resting connectivity with the executive control network in smokers. Neuropsychopharmacology, 2016, 41(10), 2557-2565. doi: 10.1038/npp.2016.62 PMID: 27112116
  10. Loonen, A.J.M.; Ivanova, S.A. New insights into the mechanism of drug-induced dyskinesia. CNS Spectr., 2013, 18(1), 15-20. doi: 10.1017/S1092852912000752 PMID: 23593652
  11. Mahmoudi, S.; Lévesque, D.; Blanchet, P.J. Upregulation of dopamine D3, not D2, receptors correlates with tardive dyskinesia in a primate model. Mov. Disord., 2014, 29(9), 1125-1133. doi: 10.1002/mds.25909 PMID: 24838395
  12. Mahadik, S.P.; Mukherjee, S. Free radical pathology and antioxidant defense in Schizophrenia: A review. Schizophr. Res., 1996, 19(1), 1-17. doi: 10.1016/0920-9964(95)00049-6 PMID: 9147491
  13. Sakamoto, T.; Imai, H. Hydrogen peroxide produced by superoxide dismutase SOD-2 activates sperm in Caenorhabditis elegans. J. Biol. Chem., 2017, 292(36), 14804-14813. doi: 10.1074/jbc.M117.788901 PMID: 28724632
  14. Tsai, G.; Goff, D.C.; Chang, R.W.; Flood, J.; Baer, L.; Coyle, J.T. Markers of glutamatergic neurotransmission and oxidative stress associated with tardive dyskinesia. Am. J. Psychiatry, 1998, 155(9), 1207-1213. doi: 10.1176/ajp.155.9.1207 PMID: 9734544
  15. Lindholm, E.; Ekholm, B.; Shaw, S.; Jalonen, P.; Johansson, G.; Pettersson, U.; Sherrington, R.; Adolfsson, R.; Jazin, E. A schizophrenia-susceptibility locus at 6q25, in one of the world’s largest reported pedigrees. Am. J. Hum. Genet., 2001, 69(1), 96-105. doi: 10.1086/321288 PMID: 11389481
  16. Shimoda-Matsubayashi, S.; Matsumine, H.; Kobayashi, T.; Nakagawa-Hattori, Y.; Shimizu, Y.; Mizuno, Y. Structural dimorphism in the mitochondrial targeting sequence in the human manganese superoxide dismutase gene. A predictive evidence for conformational change to influence mitochondrial transport and a study of allelic association in Parkinson’s disease. Biochem. Biophys. Res. Commun., 1996, 226(2), 561-565. doi: 10.1006/bbrc.1996.1394 PMID: 8806673
  17. Rosenblum, J.S.; Gilula, N.B.; Lerner, R.A. On signal sequence polymorphisms and diseases of distribution. Proc. Natl. Acad. Sci. , 1996, 93(9), 4471-4473. doi: 10.1073/pnas.93.9.4471 PMID: 8633092
  18. Hori, H.; Ohmori, O.; Shinkai, T.; Kojima, H.; Okano, C.; Suzuki, T.; Nakamura, J. Manganese superoxide dismutase gene polymorphism and schizophrenia: Relation to tardive dyskinesia. Neuropsychopharmacology, 2000, 23(2), 170-177. doi: 10.1016/S0893-133X(99)00156-6 PMID: 10882843
  19. Gałecki, P.; Pietras, T.; Szemraj, J. Manganese superoxide dismutase gene (MnSOD) polimorphism in schizophrenics with tardive dyskinesia from central Poland. Psychiatr. Pol., 2006, 40(5), 937-948. PMID: 17217237
  20. Zhang, Z.; Zhang, X.; Hou, G.; Sha, W.; Reynolds, G.P. The increased activity of plasma manganese superoxide dismutase in tardive dyskinesia is unrelated to the Ala-9Val polymorphism. J. Psychiatr. Res., 2002, 36(5), 317-324. doi: 10.1016/S0022-3956(02)00007-9 PMID: 12127599
  21. Akyol, O.; Yanik, M.; Elyas, H.; Namli, M.; Canatan, H.; Akin, H.; Yuce, H.; Yilmaz, H.R.; Tutkun, H.; Sogut, S.; Herken, H.; Özyurt, H.; Savas, H.A.; Zoroglu, S.S. Association between Ala-9Val polymorphism of Mn-SOD gene and schizophrenia. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2005, 29(1), 123-131. doi: 10.1016/j.pnpbp.2004.10.014 PMID: 15610954
  22. Pae, C.U.; Kim, T.S.; Patkar, A.A.; Kim, J.J.; Lee, C.U.; Lee, S.J.; Jun, T.Y.; Lee, C.; Paik, I.H. Manganese superoxide dismutase (MnSOD: Ala-9Val) gene polymorphism may not be associated with schizophrenia and tardive dyskinesia. Psychiatry Res., 2007, 153(1), 77-81. doi: 10.1016/j.psychres.2006.04.011 PMID: 17582511
  23. Hitzeroth, A.; Niehaus, D.J.H.; Koen, L.; Botes, W.C.; Deleuze, J.F.; Warnich, L. Association between the MnSOD Ala-9Val polymorphism and development of schizophrenia and abnormal involuntary movements in the Xhosa population. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2007, 31(3), 664-672. doi: 10.1016/j.pnpbp.2006.12.019 PMID: 17291655
  24. Kang, S.G.; Choi, J.E.; An, H.; Park, Y.M.; Lee, H.J.; Han, C.; Kim, Y.K.; Kim, S.H.; Cho, S.N.; Joe, S.H.; Jung, I.K.; Kim, L.; Lee, M.S. Manganese superoxide dismutase gene Ala-9Val polymorphism might be related to the severity of abnormal involuntary movements in Korean schizophrenic patients. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2008, 32(8), 1844-1847. doi: 10.1016/j.pnpbp.2008.08.013 PMID: 18790709
  25. Thelma, B.K.; Tiwari, A.K.; Deshpande, S.N.; Lerer, B.; Nimgaonkar, V.L. Genetic susceptibility to Tardive Dyskinesia in chronic schizophrenia subjects: Role of oxidative stress pathway genes. Schizophr. Res., 2007, 92(1-3), 278-279. doi: 10.1016/j.schres.2006.12.019 PMID: 17317105
  26. Bakker, P.R.; van Harten, P.N.; van Os, J. Antipsychotic-induced tardive dyskinesia and polymorphic variations in COMT, DRD2, CYP1A2 and MnSOD genes: A meta-analysis of pharmacogenetic interactions. Mol. Psychiatry, 2008, 13(5), 544-556. doi: 10.1038/sj.mp.4002142 PMID: 18180754
  27. Wang, D.F.; Cao, B.; Xu, M.Y.; Liu, Y.Q.; Yan, L.L.; Liu, R.; Wang, J.Y.; Lu, Q.B. Meta-analyses of manganese superoxide dismutase activity, gene Ala-9Val polymorphism, and the risk of schizophrenia. Medicine , 2015, 94(36), e1507. doi: 10.1097/MD.0000000000001507 PMID: 26356721
  28. Zhang, Z.J.; Zhang, X.B.; Hou, G.; Yao, H.; Reynolds, G.P. Interaction between polymorphisms of the dopamine D3 receptor and manganese superoxide dismutase genes in susceptibility to tardive dyskinesia. Psychiatr. Genet., 2003, 13(3), 187-192. doi: 10.1097/00041444-200309000-00010 PMID: 12960753
  29. Liu, H.; Wang, C.; Chen, P.H.; Zhang, B.S.; Zheng, Y.L.; Zhang, C.X.; Meng, H.Q.; Wang, Y.; Chen, D.C.; Xiu, M.H.; Kosten, T.R.; Zhang, X.Y. Association of the manganese superoxide dismutase gene Ala-9Val polymorphism with clinical phenotypes and tardive dyskinesia in schizophrenic patients. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2010, 34(4), 692-696. doi: 10.1016/j.pnpbp.2010.03.026 PMID: 20346996
  30. Ponto, L.B.; Schultz, S. Ginkgo biloba extract: Review of CNS effects. Ann. Clin. Psychiatry, 2003, 15(2), 109-119. doi: 10.3109/10401230309085676 PMID: 12938868
  31. DeFeudis, F.; Drieu, K. Ginkgo biloba extract (EGb 761) and CNS functions: Basic studies and clinical applications. Curr. Drug Targets, 2000, 1(1), 25-58. doi: 10.2174/1389450003349380 PMID: 11475535
  32. Zhang, W.F.; Tan, Y.L.; Zhang, X.Y.; Chan, R.C.K.; Wu, H.R.; Zhou, D.F. Extract of Ginkgo biloba treatment for tardive dyskinesia in schizophrenia: A randomized, double-blind, placebo-controlled trial. J. Clin. Psychiatry, 2011, 72(5), 615-621. doi: 10.4088/JCP.09m05125yel PMID: 20868638
  33. Montes, P.; Ruiz-Sanchez, E.; Rojas, C.; Rojas, P. Ginkgo biloba extract 761: A review of basic studies and potential clinical use in psychiatric disorders. CNS Neurol. Disord. Drug Targets, 2015, 14(1), 132-149. doi: 10.2174/1871527314666150202151440 PMID: 25642989
  34. Ihl, R. Effects of Ginkgo biloba extract EGb761® in dementia with neuropsychiatric features: Review of recently completed randomised, controlled trials. Int. J. Psychiatry Clin. Pract., 2013, 17(S1), 8-14. doi: 10.3109/13651501.2013.814796 PMID: 23808613
  35. Gauthier, S.; Schlaefke, S. Efficacy and tolerability of Ginkgo biloba extract EGb761® in dementia: A systematic review and meta-analysis of randomized placebo-controlled trials. Clin. Interv. Aging, 2014, 9, 2065-2077. doi: 10.2147/CIA.S72728 PMID: 25506211
  36. Tan, M.S.; Yu, J.T.; Tan, C.C.; Wang, H.F.; Meng, X.F.; Wang, C.; Jiang, T.; Zhu, X.C.; Tan, L. Efficacy and adverse effects of ginkgo biloba for cognitive impairment and dementia: A systematic review and meta-analysis. J. Alzheimers Dis., 2014, 43(2), 589-603. doi: 10.3233/JAD-140837 PMID: 25114079
  37. Ji, H.; Zhou, X.; Wei, W.; Wu, W.; Yao, S. Ginkgol Biloba extract as an adjunctive treatment for ischemic stroke. Medicine , 2020, 99(2), e18568. doi: 10.1097/MD.0000000000018568 PMID: 31914035
  38. Diamond, B.J.; Bailey, M.R. Ginkgo biloba. Psychiatr. Clin. North Am., 2013, 36(1), 73-83. doi: 10.1016/j.psc.2012.12.006 PMID: 23538078
  39. Zheng, W.; Xiang, Y.Q.; Ng, C.; Ungvari, G.; Chiu, H.; Xiang, Y.T. Extract of Ginkgo biloba for Tardive Dyskinesia: Meta-analysis of randomized controlled trials. Pharmacopsychiatry, 2016, 49(3), 107-111. doi: 10.1055/s-0042-102884 PMID: 26979525
  40. Kam, I.W.; Chung, W.S.D.; Liu, S.; Fong, S. The Chinese-bilingual SCID-I/P project: Stage 1 - Reliability for mood disorders and schizophrenia. Hong Kong J. Psychiatry, 2003, 13(1)
  41. Kane, J.M.; Kane, J.M. Research diagnoses for tardive dyskinesia. Arch. Gen. Psychiatry, 1982, 39(4), 486-487. doi: 10.1001/archpsyc.1982.04290040080014 PMID: 6121550
  42. Fan, B. The Chinese version of the Abnormal Involuntary Movement Scale (AIMS). 1984, 2, 80-81.
  43. SI T.; Yang, J.; Shu, L. The reliability, validity of PANSS and its implication. Chinese Mental Health Journal, 1992, 1992(12)
  44. Ōyanagui, Y. Reevaluation of assay methods and establishment of kit for superoxide dismutase activity. Anal. Biochem., 1984, 142(2), 290-296. doi: 10.1016/0003-2697(84)90467-6 PMID: 6099057
  45. Wu, J.Q.; Kosten, T.R.; Zhang, X.Y. Free radicals, antioxidant defense systems, and schizophrenia. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2013, 46, 200-206. doi: 10.1016/j.pnpbp.2013.02.015 PMID: 23470289
  46. Mahadevan, S.; Park, Y. Multifaceted therapeutic benefits of Ginkgo biloba L.: Chemistry, efficacy, safety, and uses. J. Food Sci., 2008, 73(1), R14-R19. doi: 10.1111/j.1750-3841.2007.00597.x PMID: 18211362
  47. Loonen, A.J.M.; van Praag, H.M. Measuring movement disorders in antipsychotic drug trials: The need to define a new standard. J. Clin. Psychopharmacol., 2007, 27(5), 423-430. doi: 10.1097/jcp.0b013e31814f1105 PMID: 17873670
  48. Kane, J.M.; Correll, C.U.; Nierenberg, A.A.; Caroff, S.N.; Sajatovic, M. Revisiting the abnormal involuntary movement scale. J. Clin. Psychiatry, 2018, 79(3), 17cs11959. doi: 10.4088/JCP.17cs11959 PMID: 29742330
  49. Shimoda-Matsubayashi, S.; Hattori, T.; Matsumine, H.; Shinohara, A.; Yoritaka, A.; Mori, H.; Kondo, T.; Chiba, M.; Mizuno, Y. Mn SOD activity and protein in a patient with chromosome 6-linked autosomal recessive parkinsonism in comparison with Parkinson’s disease and control. Neurology, 1997, 49(5), 1257-1262. doi: 10.1212/WNL.49.5.1257 PMID: 9371904
  50. Bresciani, G.; Cruz, I.B.M.; de Paz, J.A.; Cuevas, M.J.; González-Gallego, J. The MnSOD Ala16Val SNP: Relevance to human diseases and interaction with environmental factors. Free Radic. Res., 2013, 47(10), 781-792. doi: 10.3109/10715762.2013.836275 PMID: 23952573
  51. Zeng, K.; Li, M.; Hu, J.; Mahaman, Y.A.R.; Bao, J.; Huang, F.; Xia, Y.; Liu, X.; Wang, Q.; Wang, J.Z.; Yang, Y.; Liu, R.; Wang, X. Ginkgo biloba extract EGb761 attenuates hyperhomocysteinemia-induced AD like Tau hyperphosphorylation and cognitive impairment in rats. Curr. Alzheimer Res., 2017, 15(1), 89-99. doi: 10.2174/1567205014666170829102135 PMID: 28847282
  52. Kwon, K.J.; Lee, E.J.; Cho, K.S.; Cho, D.H.; Shin, C.Y.; Han, S.H. Ginkgo biloba extract (Egb761) attenuates zinc-induced tau phosphorylation at Ser262 by regulating GSK3β activity in rat primary cortical neurons. Food Funct., 2015, 6(6), 2058-2067. doi: 10.1039/C5FO00219B PMID: 26032477
  53. Loonen, A.J.M.; Doorschot, C.H.; van Hemert, D.A.; Oostelbos, M.C.J.M.; Sijben, A.E.S. The schedule for the assessment of drug-induced movement disorders (SADIMoD): Inter-rater reliability and construct validity. Int. J. Neuropsychopharmacol., 2001, 4(4), 347-360. doi: 10.1017/S1461145701002589 PMID: 11806860
  54. Loonen, A.J.M.; Doorschot, C.H.; van Hemert, D.A.; Oostelbos, M.C.J.M.; Sijben, A.E.S. The Schedule for the Assessment of Drug-Induced Movement Disorders (SADIMoD): Test-retest reliability and concurrent validity. Int. J. Neuropsychopharmacol., 2000, 3(4), 285-296. doi: 10.1017/S1461145700002066 PMID: 11343606
  55. Stacy, M.; Sajatovic, M.; Kane, J.M.; Cutler, A.J.; Liang, G.S.; O’Brien, C.F.; Correll, C.U. Abnormal involuntary movement scale in tardive dyskinesia: Minimal clinically important difference. Mov. Disord., 2019, 34(8), 1203-1209. doi: 10.1002/mds.27769 PMID: 31234240

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