title: Cognitive impairment and in vivo metabolites in first-episode neuroleptic-naive and chronic medicated schizophrenic patients: a proton magnetic resonance spectroscopy study.
abstract: Involvement of the prefrontal cortex in schizophrenia has been implicated by neuropsychological, as well as neuropathological and imaging studies. Reductions of N-acetylaspartate (NAA), an in vivo marker of neuronal integrity, have repeatedly been detected in the frontal lobes of patients with schizophrenia by proton magnetic resonance spectroscopy (1H-MRS). In chronic medicated patients, a positive correlation between NAA levels of the prefrontal cortex and cognitive functioning has been observed, but to date, there have been no studies in first-episode neuroleptic-naive patients. In this study, single-voxel 1H-MRS was used to investigate neuronal function of the dorsolateral prefrontal cortex in 15 first-episode and 20 chronic schizophrenic patients. Outcomes were compared to 20 age-matched healthy controls to assess the relationship between prefrontal metabolism and neuropsychological performance. Patients with chronic schizophrenia had significant reductions of NAA, glutamate/glutamine, and choline levels compared to first-episode patients and healthy controls. Furthermore, creatine and phosphocreatine were significantly reduced in both patient groups compared to healthy controls. In the neuropsychological tests, chronic schizophrenic patients performed significantly poorer in the Auditory Verbal Learning Task (AVLT) compared to first-episode patients. In both patient groups, NAA levels of the left frontal lobe significantly correlated with performances in verbal learning and memory. These results corroborate data from recent structural and spectroscopic imaging studies of the frontal lobes in schizophrenia, in which cortical gray matter reductions after onset of symptoms as well as reduced levels of NAA in chronic, but not in first-episode schizophrenic patients have been reported.
authors.affiliation: Department of Psychiatry, University of Muenster, Albert-Schweitzer Strasse 11, D-48149 Muenster, NRW, Germany. ohrmann@uni-muenster.de
authors.forename: Patricia
authors.initials: P
authors.lastname: Ohrmann
authors.forename: Ansgar
authors.initials: A
authors.lastname: Siegmund
authors.forename: Thomas
authors.initials: T
authors.lastname: Suslow
authors.forename: Anya
authors.initials: A
authors.lastname: Pedersen
authors.forename: Katharina
authors.initials: K
authors.lastname: Spitzberg
authors.forename: Anette
authors.initials: A
authors.lastname: Kersting
authors.forename: Matthias
authors.initials: M
authors.lastname: Rothermundt
authors.forename: Volker
authors.initials: V
authors.lastname: Arolt
authors.forename: Walter
authors.initials: W
authors.lastname: Heindel
authors.forename: Bettina
authors.initials: B
authors.lastname: Pfleiderer
mesh_terms: D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D002794:Choline / Q000378:metabolism; D002908:Chronic Disease; D003072:Cognition Disorders / Q000188:drug therapy / Q000503:physiopathology*; D003401:Creatine / Q000378:metabolism; D004292:Dominance, Cerebral / Q000502:physiology; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology*; D005260:Female; D005625:Frontal Lobe / Q000187:drug effects / Q000503:physiopathology*; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D011939:Mental Recall / Q000187:drug effects / Q000502:physiology; D008875:Middle Aged; D009474:Neurons / Q000502:physiology; D010725:Phosphocreatine / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects / Q000503:physiopathology*; D011569:Psychiatric Status Rating Scales; D012016:Reference Values; D012559:Schizophrenia / Q000188:drug therapy / Q000503:physiopathology*; D014706:Verbal Learning / Q000187:drug effects / Q000502:physiology
chemical_list: D014150:Antipsychotic Agents; D010725:Phosphocreatine; D005973:Glutamine; D001224:Aspartic Acid; D018698:Glutamic Acid; C000179:N-acetylaspartate; D003401:Creatine; D002794:Choline