Glutamatergic neurometabolite levels in major depressive disorder: a systematic review and meta-analysis of proton magnetic resonance spectroscopy studies

Sho Moriguchi, Akihiro Takamiya, Yoshihiro Noda, Nobuyuki Horita, Masataka Wada, Sakiko Tsugawa, Eric Plitman, Yasunori Sano, Ryosuke Tarumi, Muhammad ElSalhy, Nariko Katayama, Kamiyu Ogyu, Takahiro Miyazaki, Taishiro Kishimoto, Ariel Graff-Guerrero, Jeffrey H. Meyer, Daniel M. Blumberger, Zafiris J. Daskalakis, Masaru Mimura, Shinichiro Nakajima

Research output: Contribution to journalReview article

17 Citations (Scopus)

Abstract

Alterations in glutamatergic neurotransmission are implicated in the pathophysiology of depression, and the glutamatergic system represents a treatment target for depression. To summarize the nature of glutamatergic alterations in patients with depression, we conducted a meta-analysis of proton magnetic resonance (1H-MRS) spectroscopy studies examining levels of glutamate. We used the search terms: depress* AND (MRS OR “magnetic resonance spectroscopy”). The search was performed with MEDLINE, Embase, and PsycINFO. The inclusion criteria were 1H-MRS studies comparing levels of glutamate + glutamine (Glx), glutamate, or glutamine between patients with depression and healthy controls. Standardized mean differences (SMD) were calculated to assess group differences in the levels of glutamatergic neurometabolites. Forty-nine studies met the eligibility criteria, which included 1180 patients and 1066 healthy controls. There were significant decreases in Glx within the medial frontal cortex (SMD = −0.38; 95% CI, −0.69 to −0.07) in patients with depression compared with controls. Subanalyses revealed that there was a significant decrease in Glx in the medial frontal cortex in medicated patients with depression (SMD = −0.50; 95% CI, −0.80 to −0.20), but not in unmedicated patients (SMD = −0.27; 95% CI, −0.76 to 0.21) compared with controls. Overall, decreased levels of glutamatergic metabolites in the medial frontal cortex are linked with the pathophysiology of depression. These findings are in line with the hypothesis that depression may be associated with abnormal glutamatergic neurotransmission.

Original languageEnglish
Pages (from-to)952-964
Number of pages13
JournalMolecular Psychiatry
Volume24
Issue number7
DOIs
Publication statusPublished - 2019 Jul 1

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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    Moriguchi, S., Takamiya, A., Noda, Y., Horita, N., Wada, M., Tsugawa, S., Plitman, E., Sano, Y., Tarumi, R., ElSalhy, M., Katayama, N., Ogyu, K., Miyazaki, T., Kishimoto, T., Graff-Guerrero, A., Meyer, J. H., Blumberger, D. M., Daskalakis, Z. J., Mimura, M., & Nakajima, S. (2019). Glutamatergic neurometabolite levels in major depressive disorder: a systematic review and meta-analysis of proton magnetic resonance spectroscopy studies. Molecular Psychiatry, 24(7), 952-964. https://doi.org/10.1038/s41380-018-0252-9