Elevated peripheral blood glutamate levels in major depressive disorder

Abstract

Purpose

There is growing evidence that glutamatergic signaling may be involved in major depressive disorder (MDD). In regard to peripheral blood glutamate changes in MDD, inconsistent findings have been reported. The purpose of the present study was to evaluate whether blood glutamate levels differed between MDD patients and control participants.

Materials and methods

We conducted a systematic review and meta-analysis of 12 association studies between blood glutamate levels and MDD in a total of 529 MDD patients and 590 controls. Subsequently, we conducted subgroup analyses and a meta-regression analysis to examine the sources of potential heterogeneity.

Results

A random effects model showed that blood glutamate levels were significantly higher in MDD patients than in controls (standardized mean difference=0.54, 95% CI=0.27–0.82, p=8.5×10⁻⁵) with high heterogeneity (I²=75.0%, p<0.05). Subgroup analyses showed elevated glutamate levels in MDD patients compared with controls in plasma, but not serum studies, and in studies using high-performance liquid chromatography but not with mass spectrometry for glutamate assay. A meta-regression analysis showed no effects of age, gender, medication use, sample size, and published year on blood glutamate levels.

Conclusion

Our findings suggest that altered glutamate levels may be implicated in MDD, which provides further evidence of glutamatergic dysfunction in MDD.

Keywords:

• glutamate
• major depressive disorder
• blood
• association study
• meta-analysis

Supplementary materials

Figure S1 Flow chart of the study selection process.

Table S1 Result of leave-one-out sensitivity analysis

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Acknowledgments

This work was supported in part by Japan Agency for Medical Research and Development, AMED (Tetsuro Ohmori), Grant-in-Aid for Scientific Research (C) (No 15K09809) (Shusuke Numata), and Grant-in-Aid for Young Scientists (B) (No 16K19769) (Shin-ya Watanabe).

Author contribution

Shusuke Numata designed the study. Tetsuro Ohmori and Shusuke Numata managed the research. Masatoshi Inoshita, Yukiko Tomioka, and Shin-ya Watanabe collected the data. Makoto Kinoshita, Masahito Nakataki, Atsushi Tajima, and Hidehiro Umehara undertook the statistical analysis. Masatoshi Inoshita, Masahito Nakataki, and Shusuke Numata wrote the draft. All authors contributed toward data analysis, drafting and critically revising the paper and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.