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A study of N-methyl-D-aspartate receptor gene (GRIN2B) variants as predictors of treatment-resistant major depression

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Abstract

Rationale

In clinical practice, ketamine, an antagonist of the N-methyl-d-aspartate receptor (NMDAR), is used to alleviate depressive symptoms in patients with major depressive disorder (MDD), especially in those with treatment-resistant depression (TRD). Accordingly, the human gene coding for the 2B subunit of the NMDAR (GRIN2B) is considered a promising candidate gene for MDD susceptibility.

Objectives

The primary aim of this study is to examine whether potentially functional polymorphisms of GRIN2B confer risk for MDD, and second to investigate whether GRIN2B acts as a genetic predictor for TRD in MDD patients.

Methods

We enrolled 178 TRD and 612 non-TRD patients as well as 779 healthy controls.

Results

Four potentially functional polymorphisms (rs1805502, rs890, rs1806201, and rs7301328) within GRIN2B were genotyped in all participants. The haplotype analysis found significant differences in the distribution of the G–T haplotype between the TRD and control groups (corrected P = 0.007), and the frequency of the G–T haplotype in TRD group was significantly higher than that in the controls (TRD/control ratio 0.31:0.21). Statistically significant differences in allele and genotype frequencies were detected between TRD and non-TRD groups for the rs1805502 polymorphism within GRIN2B. There was a significant allelic association between rs1805502 and TRD with an excess of the G allele in the TRD group, compared to non-TRD group (OR = 1.55, 95 % CI = 1.18–2.05, corrected P = 0.008).

Conclusions

These initial findings strengthen the hypothesis that GRIN2B not only confers susceptibility to TRD, but also plays a genetic predictor for TRD in MDD patients.

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Acknowledgments

We are deeply grateful to all the participants and the staff of the Division of Mood Disorders, Shanghai Mental Health Center, who assisted us in the implementation of the project. This work was supported by the National Natural Science Foundation of China (91232719), the “12th Five-year Plan” of National Key Technologies R&D Program (2012BAI01B04), the Shanghai Science & Technology Development Foundation (12140904200) and the National Key Clinical Disciplines at Shanghai Mental Health Center (OMA-MH2011-873). The authors thank Dr. Taylor Poor for her editorial help.

Conflict of interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China

    Chen Zhang, Zhiguo Wu, Jun Chen, Zuowei Wang, Daihui Peng, Wu Hong, Chengmei Yuan, Yifeng Xu & Yiru Fang

  2. Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, 650223, Yunnan, China

    Chen Zhang & Lin Xu

  3. Department of Neurology, Shanghai Changhai Hospital, Secondary Military Medical University, Shanghai, 200433, China

    Zezhi Li

  4. Department of Clinical Psychology, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China

    Zhen Wang & Zeping Xiao

  5. Department of Genetics, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China

    Shunying Yu

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  1. Chen Zhang
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  2. Zezhi Li
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  3. Zhiguo Wu
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  4. Jun Chen
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  11. Yifeng Xu
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  13. Zeping Xiao
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  14. Yiru Fang
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Corresponding authors

Correspondence to Zeping Xiao or Yiru Fang.

Additional information

Chen Zhang and Zezhi Li are equally contributed to this work.

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Zhang, C., Li, Z., Wu, Z. et al. A study of N-methyl-D-aspartate receptor gene (GRIN2B) variants as predictors of treatment-resistant major depression. Psychopharmacology 231, 685–693 (2014). https://doi.org/10.1007/s00213-013-3297-0

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  • DOI: https://doi.org/10.1007/s00213-013-3297-0

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