title: Region and state specific glutamate downregulation in major depressive disorder: a meta-analysis of (1)H-MRS findings.
abstract: For major depressive disorder (MDD), magnetic resonance spectroscopy ((1)H-MRS) studies of glutamate, glutamine and Glx (the composite measure of mainly glutamate and glutamine) have yielded inconclusive or seemingly inconsistent results. We therefore systematically reviewed whether in vivo concentrations of glutamate, glutamine and Glx measured with (1)H-MRS differ between MDD patients and controls. Meta-analysis including meta-regression, sensitivity, statistical heterogeneity, and publication bias analyses were conducted. Glutamate and Glx concentrations were found to be lower in the anterior cingulate cortex (ACC) in patients compared to controls (standardized mean difference (SMD) for glutamate with 95% CIs: -0.86, -1.55 to -0.17; and for Glx: -1.15, -1.86 to -0.44). In addition, Glx was decreased in all brain regions together in current episode patients (SMD: -0.62, -1.17 to -0.07). We conclude that in MDD, glutamate and possibly glutamine are downregulated primarily in the ACC and during depressive states. These results fit the central role of the ACC in depressive symptomatology and suggest that in MDD changes in glutamatergic neurotransmission are state-dependent.
authors.affiliation: Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands. j.luykx@umcutrecht.nl
authors.forename: J J
authors.initials: JJ
authors.lastname: Luykx
authors.forename: K G
authors.initials: KG
authors.lastname: Laban
authors.forename: M P
authors.initials: MP
authors.lastname: van den Heuvel
authors.forename: M P M
authors.initials: MP
authors.lastname: Boks
authors.forename: R C W
authors.initials: RC
authors.lastname: Mandl
authors.forename: R S
authors.initials: RS
authors.lastname: Kahn
authors.forename: S C
authors.initials: SC
authors.lastname: Bakker
mesh_terms: D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D003865:Major Depressive Disorder / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation / Q000502:physiology*; D004583:Electrons; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008954:Models, Biological; D011877:Radionuclide Imaging
chemical_list: D018698:Glutamic Acid