title: Increased glutamine in patients undergoing long-term treatment for schizophrenia: a proton magnetic resonance spectroscopy study at 3 T.
abstract: OBJECTIVE
  The N-methyl-d-aspartic acid receptor hypofunction model of schizophrenia predicts a paradoxical increase in synaptic glutamate release. In vivo measurement of glutamatergic neurotransmission in humans is challenging, but glutamine, the principal metabolite of synaptic glutamate, can be quantified with proton magnetic resonance spectroscopy (1H-MRS). Although a few studies have measured glutamate, glutamine, and glutamine to glutamate ratio, it is not clear which of these 1H-MRS indices of glutamatergic neurotransmission is altered in schizophrenia.
  
  
  OBJECTIVE
  To examine glutamine, glutamate, and glutamine to glutamate ratio in the dorsal anterior cingulate, as well as their relationships with symptoms and cognition in schizophrenia.
  
  
  METHODS
  Cross-sectional design using 3-T 1H-MRS in participants recruited from university-based psychiatric outpatient clinics who underwent neuroimaging at an affiliated research facility. Participants were 84 patients with a DSM-IV-TR diagnosis of schizophrenia and 81 psychiatrically healthy volunteers, matched in age, sex, ethnicity, and occupational level to the head of household of family of origin.
  
  
  METHODS
  Glutamine, glutamate, and glutamine to glutamate ratio. Also symptoms and cognition.
  
  
  RESULTS
  Glutamine was increased in the schizophrenia group (P = .01) as well as the glutamine to glutamate ratio (P = .007) but not glutamate (P = .89). Glutamine levels were positively correlated with severity of psychotic symptoms (P = .02). Choline was also increased in schizophrenia (P = .002).
  
  
  CONCLUSIONS
  Elevated glutamine, which was directly related to psychotic symptoms, is consistent with increased glutamatergic synaptic release in schizophrenia, as predicted by the N-methyl-d-aspartic acid receptor hypofunction model. Further understanding the underlying mechanism of glutamatergic dysfunction in schizophrenia may lead to new pharmacological strategies to treat psychosis.
authors.affiliation: Department of Psychiatry, University of New Mexico, Albuquerque2Department of Neurosciences, University of New Mexico, Albuquerque.
authors.forename: Juan R
authors.initials: JR
authors.lastname: Bustillo
authors.affiliation: Department of Psychiatry, University of New Mexico, Albuquerque.
authors.forename: Hongji
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Psychiatry, University of New Mexico, Albuquerque.
authors.forename: Thomas
authors.initials: T
authors.lastname: Jones
authors.affiliation: Department of Psychiatry, University of New Mexico, Albuquerque.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Lemke
authors.affiliation: Department of Psychiatry, University of New Mexico, Albuquerque.
authors.forename: Christopher
authors.initials: C
authors.lastname: Abbott
authors.affiliation: Department of Mathematics and Statistics, University of New Mexico, Albuquerque.
authors.forename: Clifford
authors.initials: C
authors.lastname: Qualls
authors.affiliation: Department of Psychiatry, University of New Mexico, Albuquerque2Department of Neurosciences, University of New Mexico, Albuquerque4Veterans Administration Health Care System, Albuquerque, New Mexico.
authors.forename: Jose
authors.initials: J
authors.lastname: Canive
authors.affiliation: Mind Research Network, Albuquerque, New Mexico.
authors.forename: Charles
authors.initials: C
authors.lastname: Gasparovic
mesh_terms: D000328:Adult; D002794:Choline / Q000378:metabolism; D003430:Cross-Sectional Studies; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D006179:Gyrus Cinguli / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000295:instrumentation / Q000379:methods*; D008297:Male; D011522:Protons; D012559:Schizophrenia / Q000378:metabolism* / Q000503:physiopathology; D012720:Severity of Illness Index; D013997:Time Factors
chemical_list: D011522:Protons; D005973:Glutamine; D018698:Glutamic Acid; D002794:Choline