title: GABAergic system impairment in the hippocampus and superior temporal gyrus of patients with paranoid schizophrenia: A post-mortem study.
abstract: Glutamic acid decarboxylase (GAD) is a key enzyme in GABA synthesis and alterations in GABAergic neurotransmission related to glial abnormalities are thought to play a crucial role in the pathophysiology of schizophrenia. This study aimed to identify potential differences regarding the neuropil expression of GAD between paranoid and residual schizophrenia.
  
  
  
  GAD65/67 immunostained histological sections were evaluated by quantitative densitometric analysis of GAD-immunoreactive (ir) neuropil. Regions of interest were the hippocampal formation (CA1 field and dentate gyrus [DG]), superior temporal gyrus (STG), and laterodorsal thalamic nucleus (LD). Data from 16 post-mortem schizophrenia patient samples (10 paranoid and 6 residual schizophrenia cases) were compared with those from 16 matched controls.
  
  
  
  Overall, schizophrenia patients showed a lower GAD-ir neuropil density (P=0.014), particularly in the right CA1 (P=0.033). However, the diagnostic subgroups differed significantly (P<0.001), mainly because of lower right CA1 GAD-ir neuropil density in paranoid versus residual patients (P=0.036) and controls (P<0.003). Significant GAD-ir neuropil reduction was also detected in the right STG layer V of paranoid versus residual schizophrenia cases (P=0.042). GAD-ir neuropil density correlated positively with antipsychotic dosage, particularly in CA1 (right: r=0.850, P=0.004; left: r=0.800, P=0.010).
  
  
  
  Our finding of decreased relative density of GAD-ir neuropil suggests hypofunction of the GABAergic system, particularly in hippocampal CA1 field and STG layer V of patients with paranoid schizophrenia. The finding that antipsychotic medication seems to counterbalance GABAergic hypofunction in schizophrenia patients suggests the possibility of exploring new treatment avenues which target this system.
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Magdeburg, Magdeburg, Germany; Center for Behavioral Brain Sciences, Magdeburg, Germany. Electronic address: johann.steiner@med.ovgu.de.
authors.forename: Johann
authors.initials: J
authors.lastname: Steiner
authors.affiliation: Department of Forensic Medicine, Medical University of Gdańsk, Gdańsk, Poland.
authors.forename: Ralf
authors.initials: R
authors.lastname: Brisch
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Magdeburg, Magdeburg, Germany; Center for Behavioral Brain Sciences, Magdeburg, Germany.
authors.forename: Kolja
authors.initials: K
authors.lastname: Schiltz
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Magdeburg, Magdeburg, Germany.
authors.forename: Henrik
authors.initials: H
authors.lastname: Dobrowolny
authors.affiliation: Institute of Neuropathology, University of Magdeburg, Magdeburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Mawrin
authors.affiliation: Department of Forensic Medicine, Medical University of Gdańsk, Gdańsk, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Krzyżanowska
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Magdeburg, Magdeburg, Germany.
authors.forename: Hans-Gert
authors.initials: HG
authors.lastname: Bernstein
authors.affiliation: Department of Forensic Medicine, Medical University of Gdańsk, Gdańsk, Poland.
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Jankowski
authors.affiliation: Center for Behavioral Brain Sciences, Magdeburg, Germany; Department of Zoology/Developmental Neurobiology, Institute of Biology, University of Magdeburg, Magdeburg, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Braun
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University Munich, Munich, Germany; Laboratory of Neuroscience (LIM27), Institute of Psychiatry, University of São Paulo, São Paulo, Brazil.
authors.forename: Andrea
authors.initials: A
authors.lastname: Schmitt
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Magdeburg, Magdeburg, Germany; Center for Behavioral Brain Sciences, Magdeburg, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Bogerts
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Magdeburg, Magdeburg, Germany; Department of Forensic Medicine, Medical University of Gdańsk, Gdańsk, Poland; Department of Zoology/Developmental Neurobiology, Institute of Biology, University of Magdeburg, Magdeburg, Germany.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Gos
mesh_terms: D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000627:therapeutic use; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D005968:Glutamate Decarboxylase / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020645:Mediodorsal Thalamic Nucleus / Q000187:drug effects / Q000378:metabolism; D008875:Middle Aged; D019581:Neuropil / Q000378:metabolism; D012563:Schizophrenia, Paranoid / Q000188:drug therapy / Q000378:metabolism*; D013702:Temporal Lobe / Q000187:drug effects / Q000378:metabolism*
chemical_list: D014150:Antipsychotic Agents; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; C401141:glutamate decarboxylase 2
keywords: GAD 65/67; Paranoid; Post-mortem; Residual; Schizophrenia