title: Glutamatergic dysfunction linked to energy and membrane lipid metabolism in frontal and anterior cingulate cortices of never treated first-episode schizophrenia patients.
abstract: BACKGROUND
  Glutamatergic dysfunction and altered membrane lipid and energy metabolism have been repeatedly demonstrated in the frontal/prefrontal and anterior cingulate cortex (ACC) in schizophrenia. Though having been already studied in animals, the presumed link between glutamatergic function and structural plasticity has not been investigated directly in the human brain yet. We measured glutamate (Glu), focal energy metabolism, and membrane phospholipid turnover to investigate main pathologies in those key brain regions of schizophrenia.
  
  
  METHODS
  (1)H- and (31)P-Chemical Shift Imaging (CSI) was combined in a single session to assess Glu and markers of energy (PCr, ATP) and membrane lipid (PME, PDE) metabolism in 31 neuroleptic-naïve first acute onset psychosis patients and 31 matched healthy controls. Multivariate analyses of covariance were used to assess disease effects on Glu and to investigate the impact of Glu alterations on phospholipid and energy metabolites.
  
  
  RESULTS
  Glu levels of patients were increased in the frontal and prefrontal cortex bilaterally and in the ACC. Higher Glu was associated with increased left frontal/prefrontal PME and right frontal/prefrontal PDE in patients, which was not observed in healthy controls. In contrast, higher Glu levels were associated with lower PCr or ATP values in the frontal/prefrontal cortex bilaterally and in the right ACC of controls. This was not observed in the right ACC and left frontal/prefrontal cortex of patients.
  
  
  CONCLUSIONS
  Frontal glutamatergic hyperactivity is disconnected from physiologically regulated energy metabolism and is associated with increased membrane breakdown in right and increased membrane restoration in left frontal and prefrontal cortical regions. As indicated by previous findings, this pathology is likely dynamic during the course of first acute illness and possibly associated with negative symptoms and cognitive impairment. Our findings underline the importance of further research on neuroprotective treatment options during the early acute or even better for the ultra-high risk state of psychotic illness.
authors.affiliation: Department of Psychiatry, Jena University Hospital, Philosophenweg 3, D-07743 Jena, Germany. Electronic address: Stefan.Smesny@med.uni-jena.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Smesny
authors.affiliation: Medical Physics Group, Department of Diagnostic and Interventional Radiology, Jena University Hospital, Philosophenweg 3, D-07740 Jena, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Gussew
authors.affiliation: Department of Psychiatry, Jena University Hospital, Philosophenweg 3, D-07743 Jena, Germany.
authors.forename: Natalie Joan
authors.initials: NJ
authors.lastname: Biesel
authors.affiliation: Department of Psychiatry, Jena University Hospital, Philosophenweg 3, D-07743 Jena, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Schack
authors.affiliation: Institute of Medical Statistics, Computer Sciences and Documentation (IMSID), Jena University Hospital, Friedrich-Schiller University Jena, Bachstraße 18, D-07743 Jena, Germany.
authors.forename: Mario
authors.initials: M
authors.lastname: Walther
authors.affiliation: Medical Physics Group, Department of Diagnostic and Interventional Radiology, Jena University Hospital, Philosophenweg 3, D-07740 Jena, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Rzanny
authors.affiliation: Department of Psychiatry, Jena University Hospital, Philosophenweg 3, D-07743 Jena, Germany; Department of Psychiatry, Thüringen-Kliniken "Georgius Agricola" GmbH Rainweg 68, D-07318 Saalfeld/Saale, Germany.
authors.forename: Berko
authors.initials: B
authors.lastname: Milleit
authors.affiliation: Department of Psychiatry, Jena University Hospital, Philosophenweg 3, D-07743 Jena, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Gaser
authors.affiliation: Department of Psychiatry, Thüringen-Kliniken "Georgius Agricola" GmbH Rainweg 68, D-07318 Saalfeld/Saale, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Sobanski
authors.affiliation: Department of Psychiatry, Jena University Hospital, Philosophenweg 3, D-07743 Jena, Germany.
authors.forename: Carl Christoph
authors.initials: CC
authors.lastname: Schultz
authors.affiliation: Department of Child and Adolescent Psychiatry, Medical University Vienna, Währingergürtel 18-20, A-1090 Vienna, Austria; Orygen Youth Health Research Centre, The University of Melbourne, Locked Bag 10, 35 Poplar Road Parkville, Victoria 3052, Melbourne, Australia.
authors.forename: Paul
authors.initials: P
authors.lastname: Amminger
authors.affiliation: Department of Dermatology, Jena University Hospital, Erfurter Straße 35, D-07743 Jena, Germany.
authors.forename: Uta-Christina
authors.initials: UC
authors.lastname: Hipler
authors.affiliation: Department of Psychiatry, Jena University Hospital, Philosophenweg 3, D-07743 Jena, Germany.
authors.forename: Heinrich
authors.initials: H
authors.lastname: Sauer
authors.affiliation: Medical Physics Group, Department of Diagnostic and Interventional Radiology, Jena University Hospital, Philosophenweg 3, D-07740 Jena, Germany.
authors.forename: Jürgen R
authors.initials: JR
authors.lastname: Reichenbach
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D003401:Creatine / Q000378:metabolism; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D006179:Gyrus Cinguli / Q000378:metabolism*; D006801:Humans; D050356:Lipid Metabolism; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D010759:Phosphorus Isotopes / Q000493:pharmacokinetics; D011522:Protons; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000473:pathology*; D055815:Young Adult
chemical_list: D008563:Membrane Lipids; D010743:Phospholipids; D010759:Phosphorus Isotopes; D011522:Protons; D001224:Aspartic Acid; D018698:Glutamic Acid; C000179:N-acetylaspartate; D003401:Creatine
keywords: (1)H-MRS; (31)P-MRS; CSI; Energy metabolism; First-episode psychosis; Glutamate; Phospholipids; Schizophrenia