Johann Steiner1, Ralf Brisch2, Kolja Schiltz3, Henrik Dobrowolny4, Christian Mawrin5, Marta Krzyżanowska2, Hans-Gert Bernstein4, Zbigniew Jankowski2, Katharina Braun6, Andrea Schmitt7, Bernhard Bogerts3, Tomasz Gos8. 1. Department of Psychiatry and Psychotherapy, University of Magdeburg, Magdeburg, Germany; Center for Behavioral Brain Sciences, Magdeburg, Germany. Electronic address: johann.steiner@med.ovgu.de. 2. Department of Forensic Medicine, Medical University of Gdańsk, Gdańsk, Poland. 3. Department of Psychiatry and Psychotherapy, University of Magdeburg, Magdeburg, Germany; Center for Behavioral Brain Sciences, Magdeburg, Germany. 4. Department of Psychiatry and Psychotherapy, University of Magdeburg, Magdeburg, Germany. 5. Institute of Neuropathology, University of Magdeburg, Magdeburg, Germany. 6. Center for Behavioral Brain Sciences, Magdeburg, Germany; Department of Zoology/Developmental Neurobiology, Institute of Biology, University of Magdeburg, Magdeburg, Germany. 7. 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. 8. 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.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.
BACKGROUND: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. METHODS: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 schizophreniapatient samples (10 paranoid and 6 residual schizophrenia cases) were compared with those from 16 matched controls. RESULTS: Overall, schizophreniapatients 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 CA1GAD-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). CONCLUSION: 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 schizophreniapatients suggests the possibility of exploring new treatment avenues which target this system.
Authors: Bo Cao; Raymond Y Cho; Dachun Chen; Meihong Xiu; Li Wang; Jair C Soares; Xiang Yang Zhang Journal: Mol Psychiatry Date: 2018-06-19 Impact factor: 15.992
Authors: Nina Vanessa Kraguljac; Matthew Carle; Michael A Frölich; Steve Tran; Michael A Yassa; David Matthew White; Abhishek Reddy; Adrienne Carol Lahti Journal: Biol Psychiatry Cogn Neurosci Neuroimaging Date: 2021-10-12
Authors: Kenneth N Fish; Brad R Rocco; Adam M DeDionisio; Samuel J Dienel; Robert A Sweet; David A Lewis Journal: Biol Psychiatry Date: 2021-02-19 Impact factor: 12.810
Authors: Natalie Matosin; Francesca Fernandez-Enright; Jeremy S Lum; Martin Engel; Jessica L Andrews; Nils C Gassen; Klaus V Wagner; Mathias V Schmidt; Kelly A Newell Journal: NPJ Schizophr Date: 2016-06-29
Authors: Przemysław Adamczyk; Miroslaw Wyczesany; Aleksandra Domagalik; Artur Daren; Kamil Cepuch; Piotr Błądziński; Andrzej Cechnicki; Tadeusz Marek Journal: Neuroimage Clin Date: 2017-06-03 Impact factor: 4.881
Authors: Nina Vanessa Kraguljac; Matthew Carle; Michael A Frölich; Steve Tran; Michael A Yassa; David Matthew White; Abhishek Reddy; Adrienne Carol Lahti Journal: Biol Psychiatry Cogn Neurosci Neuroimaging Date: 2017-02-28
Authors: Tiago Reis Marques; Abhishekh H Ashok; Ilinca Angelescu; Faith Borgan; Jim Myers; Anne Lingford-Hughes; David J Nutt; Mattia Veronese; Federico E Turkheimer; Oliver D Howes Journal: Mol Psychiatry Date: 2020-04-15 Impact factor: 13.437