title: Glutamatergic and Neuronal Dysfunction in Gray and White Matter: A Spectroscopic Imaging Study in a Large Schizophrenia Sample.
abstract: Glutamine plus glutamate (Glx), as well as N-acetylaspartate compounds (NAAc, N-acetylaspartate plus N-acetyl-aspartyl-glutamate), a marker of neuronal viability, can be quantified with proton magnetic resonance spectroscopy (1H-MRS). We used 1H-MRS imaging to assess Glx and NAAc, as well as total-choline (glycerophospho-choline plus phospho-choline), myo-inositol and total-creatine (creatine plus phosphocreatine) from an axial supraventricular slab of gray matter (GM, medial-frontal and medial-parietal) and white matter (WM, bilateral-frontal and bilateral-parietal) voxels. Schizophrenia subjects (N = 104) and healthy controls (N = 97) with a broad age range (16 to 65) were studied. In schizophrenia, Glx was increased in GM (P < .001) and WM (P = .01), regardless of age. However, with greater age, NAAc increased in GM (P < .001) but decreased in WM (P < .001) in schizophrenia. In patients, total creatine decreased with age in WM (P < .001). Finally, overall cognitive score correlated positively with WM neurometabolites in controls but negatively in the schizophrenia group (NAAc, P < .001; and creatine [only younger], P < .001). We speculate the results support an ongoing process of increased glutamate metabolism in schizophrenia. Later in the illness, disease progression is suggested by increased cortical compaction without neuronal loss (elevated NAAc) and reduced axonal integrity (lower NAAc). Furthermore, this process is associated with fundamentally altered relationships between neurometabolite concentrations and cognitive function in schizophrenia.
authors.affiliation: Department of Psychiatry, University of New Mexico, Albuquerque, NM, USA.|Department of Neurosciences, University of New Mexico, Albuquerque, NM, USA.
authors.forename: Juan R
authors.initials: JR
authors.lastname: Bustillo
authors.affiliation: Department of Psychiatry, University of New Mexico, Albuquerque, NM, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Jones
authors.affiliation: Department of Psychiatry, University of New Mexico, Albuquerque, NM, USA.
authors.forename: Hongji
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Psychiatry, University of New Mexico, Albuquerque, NM, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Lemke
authors.affiliation: Department of Psychiatry, University of New Mexico, Albuquerque, NM, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Abbott
authors.affiliation: Department of Mathematics & Statistics, University of New Mexico, Albuquerque, NM, USA.
authors.forename: Clifford
authors.initials: C
authors.lastname: Qualls
authors.affiliation: Department of Psychiatry, University of New Mexico, Albuquerque, NM, USA.
authors.forename: Shannon
authors.initials: S
authors.lastname: Stromberg
authors.affiliation: Department of Psychiatry, University of New Mexico, Albuquerque, NM, USA.|Department of Neurosciences, University of New Mexico, Albuquerque, NM, USA.|Department of Psychiatry, VA Health Care System, Albuquerque, NM, USA.
authors.forename: Jose
authors.initials: J
authors.lastname: Canive
authors.affiliation: Mind Research Network, Albuquerque, NM, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Gasparovic
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D002794:Choline / Q000378:metabolism*; D003401:Creatine / Q000378:metabolism*; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D066128:Gray Matter / Q000000981:diagnostic imaging / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D066244:Proton Magnetic Resonance Spectroscopy / Q000379:methods*; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000378:metabolism*; D066127:White Matter / Q000000981:diagnostic imaging / Q000378:metabolism*; D055815:Young Adult
chemical_list: D005973:Glutamine; D001224:Aspartic Acid; D018698:Glutamic Acid; C000179:N-acetylaspartate; D003401:Creatine; D002794:Choline
keywords: 1H-MRS; N-acetylaspartate; creatine; glutamate; schizophrenia; total-choline