title: Interaction of hippocampal volume and N-acetylaspartate concentration deficits in schizophrenia: a combined MRI and 1H-MRS study.
abstract: BACKGROUND
  Volume deficits assessed with magnetic resonance imaging (MRI) and neurochemical dysfunctions (N-acetylaspartate, NAA) diagnosed using proton MR spectroscopy ((1)H-MRS) are reliable observations in the hippocampus of schizophrenic patients. NAA is an important cerebral amino acid in the synthesis pathways of glutamate, which has been implicated as a pathobiological core of schizophrenic symptomatology, of histological alterations and brain volume deficits in schizophrenia. However, the possible interaction between regional NAA reduction and volume deficits has been targeted only marginally in previous investigations.
  
  
  METHODS
  In 29 schizophrenic patients and 44 control subjects, a multimodal imaging study with (1)H-MRS and MRI volumetry of the left hippocampus was performed on a 3-Tesla scanner.
  
  
  RESULTS
  Compared to the control group, the hippocampus of the patients exhibited a significant volume reduction and a significant NAA concentration decrease. In schizophrenic patients, but not in healthy controls, a significant negative correlation between hippocampal NAA concentration and volume (r=-0.455, p=0.017) was observed. None of the imaging parameters was associated with clinical parameters.
  
  
  CONCLUSIONS
  The results argue for a coexistent neurochemical and structural deficit in the hippocampus of schizophrenic patients. The inverse relationship between the two parameters observed in patients only may reflect an interaction of neurochemistry and brain morphology as a pathobiological mechanism in schizophrenia. This observation is compatible with the important role of NAA in the synthesis of excitatory neurotransmitters and the hypothesized role of glutamate for brain morphology. The independence of the measured imaging parameters from clinical parameters is in line with the neurodevelopmental hypothesis of schizophrenia.
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité-University Medicine Berlin, Campus Mitte, Berlin, Germany. andreas.klaer@charite.de
authors.forename: Andreas Arthur
authors.initials: AA
authors.lastname: Klär
authors.forename: Martina
authors.initials: M
authors.lastname: Ballmaier
authors.forename: Karolina
authors.initials: K
authors.lastname: Leopold
authors.forename: Ines
authors.initials: I
authors.lastname: Häke
authors.forename: Martin
authors.initials: M
authors.lastname: Schaefer
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Brühl
authors.forename: Florian
authors.initials: F
authors.lastname: Schubert
authors.forename: Jürgen
authors.initials: J
authors.lastname: Gallinat
mesh_terms: D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D005260:Female; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D009929:Organ Size; D011522:Protons; D012559:Schizophrenia / Q000378:metabolism* / Q000473:pathology*; D014018:Tissue Distribution
chemical_list: D011522:Protons; D001224:Aspartic Acid; C000179:N-acetylaspartate