Fatemi S Hossein, Folsom Timothy D, Thuras Paul D
Department of Psychiatry, Division of Neuroscience Research, University of Minnesota Medical School, 420 Delaware St. SE, MMC 392, Minneapolis, Minnesota, 55455.
Department of Neuroscience, University of Minnesota Medical School, 321 Church St. SE, Minneapolis, Minnesota, 55455.
Synapse. 2017 Jul;71(7). doi: 10.1002/syn.21973. Epub 2017 Apr 5.
Schizophrenia and bipolar disorder are complex psychiatric disorders that affect millions of people worldwide. Evidence from gene association and postmortem studies has identified abnormalities of the gamma-aminobutyric acid (GABA) signaling system in both disorders. Abnormal GABAergic signaling and transmission could contribute to the symptomatology of these disorders, potentially through impaired gamma oscillations which normally occur during cognitive processing. In the current study, we examined the protein expression of 14 GABA and two GABA receptor subunits in the superior frontal cortex of subjects with schizophrenia, bipolar disorder, and healthy controls. Analyses of Variance (ANOVAs) identified significant group effects for protein levels for the α1, α6, β1, β3, δ, ɛ, and π GABA receptor subunits and R1 and R2 GABA receptor subunits. Follow-up t tests confirmed changes for these subunits in subjects with schizophrenia, subjects with bipolar disorder, or both groups. Alterations in stoichiometry of GABA receptor subunits could result in altered ligand binding, transmission, and pharmacology of GABA receptors in superior frontal cortex. Thus, impaired GABAergic transmission may negatively contribute to symptoms such as anxiety or panic as well as impaired learning and information processing, all of which are disrupted in schizophrenia and bipolar disorder. Taken together, these results provide additional evidence of GABAergic receptor abnormalities in these disorders.
精神分裂症和双相情感障碍是复杂的精神疾病，影响着全球数百万人。基因关联研究和尸检研究的证据已确定这两种疾病中γ-氨基丁酸（GABA）信号系统存在异常。异常的GABA能信号传导和传递可能导致这些疾病的症状，可能是通过认知加工过程中通常会出现的γ振荡受损。在本研究中，我们检测了精神分裂症患者、双相情感障碍患者和健康对照者额叶上皮质中14种GABA和两种GABA受体亚基的蛋白表达。方差分析（ANOVA）确定了α1、α6、β1、β3、δ、ɛ和π GABA受体亚基以及R1和R2 GABA受体亚基的蛋白水平存在显著的组间效应。后续的t检验证实了精神分裂症患者、双相情感障碍患者或两组患者中这些亚基的变化。GABA受体亚基化学计量的改变可能导致额叶上皮质中GABA受体的配体结合、传递和药理学发生改变。因此，GABA能传递受损可能对焦虑或恐慌等症状以及学习和信息处理受损产生负面影响，而这些在精神分裂症和双相情感障碍中均受到破坏。综上所述，这些结果为这些疾病中GABA能受体异常提供了更多证据。
