Steiner Johann, Brisch Ralf, Schiltz Kolja, Dobrowolny Henrik, Mawrin Christian, Krzyżanowska Marta, Bernstein Hans-Gert, Jankowski Zbigniew, Braun Katharina, Schmitt Andrea, Bogerts Bernhard, Gos Tomasz
Department of Psychiatry and Psychotherapy, University of Magdeburg, Magdeburg, Germany; Center for Behavioral Brain Sciences, Magdeburg, Germany.
Department of Forensic Medicine, Medical University of Gdańsk, Gdańsk, Poland.
Schizophr Res. 2016 Nov;177(1-3):10-17. doi: 10.1016/j.schres.2016.02.018. Epub 2016 Feb 26.
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.
谷氨酸脱羧酶（GAD）是γ-氨基丁酸（GABA）合成中的关键酶，与神经胶质细胞异常相关的GABA能神经传递改变被认为在精神分裂症的病理生理学中起关键作用。本研究旨在确定偏执型精神分裂症和残留型精神分裂症之间GAD在神经毡表达方面的潜在差异。
通过对GAD免疫反应性（ir）神经毡进行定量光密度分析，评估GAD65/67免疫染色的组织学切片。感兴趣的区域是海马结构（CA1区和齿状回[DG]）、颞上回（STG）和丘脑外侧背核（LD）。将16例死后精神分裂症患者样本（10例偏执型和6例残留型精神分裂症病例）的数据与16例匹配对照的数据进行比较。
总体而言，精神分裂症患者的GAD-ir神经毡密度较低（P = 0.014），尤其是在右侧CA1区（P = 0.033）。然而，诊断亚组存在显著差异（P < 0.001），主要是因为偏执型患者与残留型患者及对照相比，右侧CA1区的GAD-ir神经毡密度较低（偏执型与残留型患者相比，P = 0.036；与对照相比，P < 0.003）。在偏执型与残留型精神分裂症病例的右侧STG第V层中也检测到GAD-ir神经毡显著减少（P = 0.042）。GAD-ir神经毡密度与抗精神病药物剂量呈正相关，尤其是在CA1区（右侧：r = 0.850，P = 0.004；左侧：r = 0.800，P = 0.010）。
我们发现GAD-ir神经毡相对密度降低表明GABA能系统功能减退，尤其是在偏执型精神分裂症患者的海马CA1区和STG第V层。抗精神病药物似乎能抵消精神分裂症患者GABA能功能减退这一发现提示了探索针对该系统的新治疗途径的可能性。
