title: Age-related increases in basal ganglia glutamate are associated with TNF, reduced motivation and decreased psychomotor speed during IFN-alpha treatment: Preliminary findings.
abstract: Inflammation-induced alterations in central nervous system (CNS) metabolism have focused on glutamate. At excessive concentrations, glutamate is toxic to glia and neurons, and inflammatory cytokines have been shown to influence glutamate turnover by blocking glutamate reuptake and increasing glutamate release. Increased glutamate has also been found in depression, a disorder associated with increased inflammation. Data by our group have shown increased glutamate as measured by magnetic resonance spectroscopy (MRS) in basal ganglia and dorsal anterior cingulate cortex of patients administered the inflammatory cytokine interferon (IFN)-alpha. Given data that increasing age is associated with an exaggerated CNS inflammatory response, we examined whether older age (>55years) would be associated with a greater IFN-alpha-induced increase in CNS glutamate. Using a longitudinal design, 31 patients with hepatitis C virus (HCV) underwent MRS, blood sampling for inflammatory markers, and behavioral assessments before (Visit 1) and after 4weeks (Visit 2) of either IFN-alpha (n=17) or no treatment (n=14). Older patients treated with IFN-alpha exhibited a significantly greater increase in glutamate from Visit 1 to Visit 2 as reflected by the glutamate/creatine ratio (Glu/Cr) in left basal ganglia compared to older controls and younger IFN-alpha-treated and untreated subjects. In addition, increased Glu/Cr in older but not younger IFN-alpha-treated and untreated patients was associated with increased tumor necrosis factor, reduced motivation as measured by the Multidimensional Fatigue Inventory and increased choice movement time on the Cambridge Neuropsychological Test Automated Battery. Taken together, these preliminary data support the notion that older age may interact with inflammation to exaggerate the effects of inflammatory stimuli on CNS glutamate and behavior.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, United States.
authors.forename: Ebrahim
authors.initials: E
authors.lastname: Haroon
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, United States.
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Felger
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, United States.
authors.forename: Bobbi J
authors.initials: BJ
authors.lastname: Woolwine
authors.affiliation: Coulter BME Biomedical Imaging Technology Center, Emory University School of Medicine, Atlanta, GA United States.
authors.forename: Xiangchuan
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Medicine, Division of Digestive Diseases, Emory University School of Medicine, Atlanta, GA, United States.
authors.forename: Samir
authors.initials: S
authors.lastname: Parekh
authors.affiliation: Department of Medicine, Division of Digestive Diseases, Emory University School of Medicine, Atlanta, GA, United States.
authors.forename: James R
authors.initials: JR
authors.lastname: Spivey
authors.affiliation: Coulter BME Biomedical Imaging Technology Center, Emory University School of Medicine, Atlanta, GA United States.
authors.forename: Xiaoping P
authors.initials: XP
authors.lastname: Hu
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, United States.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Miller
mesh_terms: D000328:Adult; D000367:Age Factors; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001479:Basal Ganglia / Q000378:metabolism*; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D006526:Hepatitis C / Q000188:drug therapy / Q000378:metabolism / Q000523:psychology; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009042:Motivation / Q000187:drug effects / Q000502:physiology*; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology*; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D014409:Tumor Necrosis Factor-alpha; D018698:Glutamic Acid
keywords: Aging; Basal ganglia; Cytokine; Glutamate; IFN-alpha; Inflammation; Motivation; Psychomotor speed; TNF