title: Indirect evidence of selective glial involvement in glutamate-based mechanisms of mood regulation in depression: meta-analysis of absolute prefrontal neuro-metabolic concentrations.
abstract: Proton magnetic resonance spectroscopy ((1)H MRS) measures glutamatergic metabolites namely glutamate and glutamine located in neurons and astrocytes respectively. In this meta-analysis the contribution of glutamatergic neurotransmission to depressive symptoms was evaluated together with other putative prefrontal metabolites described in the pathogenesis of mood disorders, and in relation to treatment effects. A comprehensive literature search up to 2014 identified 17 reports which measured absolute concentrations of neurometabolites in the prefrontal cortex with (1)H MRS meeting criteria for inclusion in this meta-analysis. Excess of heterogeneity was investigated with meta-regressions. The analyses showed an exclusive reduction in absolute values of the composite measure of Glutamine and Glutamate (Glx) in the prefrontal cortex in depression, correlating in meta-regression analyses with treatment severity. Glutamate measurements in isolation did not differ vs. healthy controls or in relation to treatment and/or clinical improvement. Similarly there were no significant changes in other neurometabolites at baseline and following treatment. The analysis supports a role for glutamatergic dysfunction in the pathogeneses of mood dysregulation. The reduction in the absolute Glx values in the absence of changes in glutamate levels, suggests a possible modulatory role of astrocytes in the pathophysiology of depression.
authors.affiliation: Center for Affective Disorders, Institute of Psychiatry, Psychology and Neuroscience, King׳s College London, P074, 103 Denmark Hill, London SE5 8AF, United Kingdom. Electronic address: danilo.arnone@kcl.ac.uk.
authors.forename: Danilo
authors.initials: D
authors.lastname: Arnone
authors.affiliation: Department of Human Biology, School of Medicine and Health Sciences, University for Development Studies, Tamale, Ghana.
authors.forename: Abdul Nashirudeen
authors.initials: AN
authors.lastname: Mumuni
authors.affiliation: Department of Psychosis Studies, King׳s College London, Institute of Psychiatry, Psychology and Neuroscience, London, United Kingdom.
authors.forename: Sameer
authors.initials: S
authors.lastname: Jauhar
authors.affiliation: MRI Unit, Institute of Neurological Sciences, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Barrie
authors.initials: B
authors.lastname: Condon
authors.affiliation: Sackler Centre for Psychobiological Research, Institute of Health and Wellbeing, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Cavanagh
mesh_terms: D000339:Affect / Q000502:physiology*; D003866:Depressive Disorder / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D017397:Prefrontal Cortex / Q000378:metabolism*
chemical_list: D018698:Glutamic Acid
keywords: Affective disorders; Depression; Glutamate; MRS; Magnetic resonance spectroscopy; Meta-analysis