Exploring Blood Glutamate as a Diagnostic Biomarker for Major Depressive Episodes in a Context of Major Depressive Disorder

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INTRODUCTION: Major depressive disorder (MDD) represents a critical public health issue, impacting millions globally and significantly contributing to disability-adjusted life years. Major depressive episode (MDE) is a feature of MDD characterized by severe depressive symptoms. The role of glutamate, a primary excitatory neurotransmitter, in MDD has been extensively studied, and several drugs improving MDE/MDD impact the glutamate cascade; however, findings regarding blood glutamate levels in patients with a current MDE in a context of MDD remain inconsistent. This study aimed to compare blood glutamate levels between MDE/MDD patients and matched controls. METHODS: We conducted a matched case-control study utilizing 185 cases from the METADAP multicentric prospective study (NCT00526383), which was conducted from November 2009 to March 2013, and 185 controls from the VARIETE cohort (NCT01831648), conducted between January 2011 and February 2012. Blood glutamate levels were assessed from plasma samples collected between 8:00 and 10:00 a.m. after an overnight fast. The same method was used for patients and controls. RESULTS: No significant blood glutamate-level differences were observed between the 185 cases and matched controls of this study (conditional logistic regression: OR = 0.99, 95% CI: 0.98-1.01, p = 0.74). CONCLUSION: Further research is warranted to investigate brain glutamate levels and whether glutamate levels of MDE/MDD patients could predict response to conventional antidepressant drugs and anti-glutamatergic drugs such as ketamine.

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