title: Conceptual convergence: increased inflammation is associated with increased basal ganglia glutamate in patients with major depression.
abstract: Inflammation and altered glutamate metabolism are two pathways implicated in the pathophysiology of depression. Interestingly, these pathways may be linked given that administration of inflammatory cytokines such as interferon-α to otherwise non-depressed controls increased glutamate in the basal ganglia and dorsal anterior cingulate cortex (dACC) as measured by magnetic resonance spectroscopy (MRS). Whether increased inflammation is associated with increased glutamate among patients with major depression is unknown. Accordingly, we conducted a cross-sectional study of 50 medication-free, depressed outpatients using single-voxel MRS, to measure absolute glutamate concentrations in basal ganglia and dACC. Multivoxel chemical shift imaging (CSI) was used to explore creatine-normalized measures of other metabolites in basal ganglia. Plasma and cerebrospinal fluid (CSF) inflammatory markers were assessed along with anhedonia and psychomotor speed. Increased log plasma C-reactive protein (CRP) was significantly associated with increased log left basal ganglia glutamate controlling for age, sex, race, body mass index, smoking status and depression severity. In turn, log left basal ganglia glutamate was associated with anhedonia and psychomotor slowing measured by the finger-tapping test, simple reaction time task and the Digit Symbol Substitution Task. Plasma CRP was not associated with dACC glutamate. Plasma and CSF CRP were also associated with CSI measures of basal ganglia glutamate and the glial marker myoinositol. These data indicate that increased inflammation in major depression may lead to increased glutamate in the basal ganglia in association with glial dysfunction and suggest that therapeutic strategies targeting glutamate may be preferentially effective in depressed patients with increased inflammation as measured by CRP.
authors.affiliation: Emory Behavioral Immunology Program, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.|Emory Biomedical Imaging Technology Center, Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA, USA.|Winship Cancer Center, Department of Hematology and Oncology, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: E
authors.identifier: 0000-0002-8817-1116
authors.initials: E
authors.lastname: Haroon
authors.affiliation: Emory Biomedical Imaging Technology Center, Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA, USA.
authors.forename: C C
authors.initials: CC
authors.lastname: Fleischer
authors.affiliation: Emory Behavioral Immunology Program, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.|Winship Cancer Center, Department of Hematology and Oncology, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Felger
authors.affiliation: Emory Biomedical Imaging Technology Center, Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA, USA.
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.affiliation: Emory Behavioral Immunology Program, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.|Winship Cancer Center, Department of Hematology and Oncology, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: B J
authors.initials: BJ
authors.lastname: Woolwine
authors.affiliation: Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: T
authors.initials: T
authors.lastname: Patel
authors.affiliation: Emory Biomedical Imaging Technology Center, Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA, USA.
authors.forename: X P
authors.initials: XP
authors.lastname: Hu
authors.affiliation: Emory Behavioral Immunology Program, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.|Winship Cancer Center, Department of Hematology and Oncology, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: A H
authors.initials: AH
authors.lastname: Miller
mesh_terms: D000328:Adult; D001479:Basal Ganglia / Q000378:metabolism* / Q000502:physiology; D001921:Brain / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D003430:Cross-Sectional Studies; D003863:Depression / Q000188:drug therapy / Q000378:metabolism; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D006179:Gyrus Cinguli / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D016898:Interferon-alpha; D008279:Magnetic Resonance Imaging / Q000379:methods; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D008875:Middle Aged
chemical_list: D016898:Interferon-alpha; D018698:Glutamic Acid; D002097:C-Reactive Protein