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Glycogen synthase kinase-3β gene is associated with antidepressant treatment response in Chinese major depressive disorder

The Pharmacogenomics Journal volume 8, pages 384–390 (2008)Cite this article

Abstract

Evidence suggests that glycogen synthase kinase-3β (GSK3B) activity is increased significantly in the brain of patients with major depressive disorders (MDD). Inhibition of GSK3B is thought to be a key feature in the therapeutic mechanism of antidepressants. To investigate whether common genetic variants in the GSK3B gene are associated with MDD and the therapeutic response to antidepressants, four polymorphisms (rs334558 (−50 T>C), rs13321783 (IVS7+9227 A>G), rs2319398 (IVS7+11660 G>T) and rs6808874 (IVS11+4251 T>A)) of the GSK3B gene were genotyped in 230 Chinese MDD patients and 415 controls. Among the MDD patients, 168 accepted selective serotonin reuptake inhibitor (SSRI) (fluoxetine or citalopram) antidepressant treatment and therapeutic evaluation for 4 weeks and 117 for 8 weeks. Significant association with MDD was not shown in the alleles and genotypes of single loci or four-locus haplotypes. However, three of the four polymorphisms investigated were significantly associated with 4-week antidepressant therapeutic effect (P=0.002–0.011). Of the four-locus haplotype analysis, the GSK3B TAGT carriers showed a poorer response to antidepressants in 4-week (P<0.0001) and 8-week (P=0.015) evaluation compared with other haplotype groups and would quite likely be the non-remitter to 8-week antidepressant treatment (P=0.006). Our findings show, for the first time, that GSK3B genetic variants play a role in the SSRI antidepressant therapeutic response and support the hypothesis that drugs regulating GSK3B activity may represent a novel treatment strategy for MDD.

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Acknowledgements

This work was supported by Grant NSC 92-2314-B-075-087 from the National Science Council, Taiwan and Grant VGH-92-161 from the Taipei Veterans General Hospital. We thank Jer-Yuan Wu, the National Genotyping Center and the National Clinical Core at Academia Sinica, Taiwan, for genotyping support.

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Author notes

  1. S-J Tsai and Y-J Liou: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan

    S-J Tsai, Y-J Liou & C-J Hong

  2. Division of Psychiatry, School of Medicine, National Yang-Ming University, Taipei, Taiwan

    S-J Tsai & C-J Hong

  3. Department of Psychiatry, Yuli Veterans Hospital, Hualien, Taiwan

    Y-J Liou

  4. Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan

    Y-J Liou

  5. Division of Mental Health and Substance Abuse Research, National Health Research Institutes, Miaoli, Taiwan

    Y-J Liou

  6. Yu's Psychiatric Clinic, Kaohsiung, Taiwan

    Y W-Y Yu

  7. Department of Psychiatry, E-DA Hospital and I-Shou University, Kaohsiung, Taiwan

    T-J Chen

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  1. S-J Tsai
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  2. Y-J Liou
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  3. C-J Hong
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  4. Y W-Y Yu
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Corresponding author

Correspondence to S-J Tsai.

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None declared.

Supplementary Information accompanies the paper on the The Pharmacogenomics Journal website (http://www.nature.com/tpj)

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Tsai, SJ., Liou, YJ., Hong, CJ. et al. Glycogen synthase kinase-3β gene is associated with antidepressant treatment response in Chinese major depressive disorder. Pharmacogenomics J 8, 384–390 (2008). https://doi.org/10.1038/sj.tpj.6500486

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