Sex differences in GABAergic gene expression occur in the anterior cingulate cortex in schizophrenia.
Sex differences in GABAergic gene expression occur in the anterior cingulate cortex in schizophrenia.
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DOI：
10.1016/j.schres.2015.01.025
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发表时间：
2015-09
影响因子：
4.5
通讯作者：
Sodhi MS
中科院分区：
文献类型：
--
作者：
Bristow GC;Bostrom JA;Haroutunian V;Sodhi MS
GABA能功能障碍与精神分裂症的病理生理密切相关。在这项研究中，我们分析了几个GABA能基因的表达水平在前扣带皮层（ACC）的尸检受试者精神分裂症（n=21）和对照组的个人没有精神疾病史（n=18）。我们的分析揭示了性别对诊断的显著影响，沿着的是基于用药状态的GABA能基因表达的显著差异。分析显示，在男性组中，与对照组相比，精神分裂症病例中GABA能基因的表达通常较低，GABA-Aα5、GABA-Aβ1和GABA-Aε的表达水平显著较低。女性精神分裂症患者GABA能基因的表达明显增高，其中GABA-Aβ1和GAD 67基因的表达明显增高。对精神分裂症受试者的药物效应分析显示，与未用药组相比，用药组中GABA-Aα1-3、GABA-A β2、GABA-Aγ2和GAD 67的表达显著更高。这些数据表明，性别差异的GABA能基因的表达发生在ACC精神分裂症。因此，我们的数据支持以前的发现GABA能功能障碍的精神分裂症，并强调考虑性别的重要性，在分析精神分裂症的病理生理。GABA能调节ACC功能的性别差异可能导致男性和女性精神分裂症患者症状的差异。此外，我们的研究结果表明，抗精神病药物可能会改变ACC中的GABA能信号，支持GABA能靶点用于开发新型抗精神病药物的潜力。
GABAergic dysfunction has been strongly implicated in the pathophysiology of schizophrenia. In this study, we analyzed the expression levels of several GABAergic genes in the anterior cingulate cortex (ACC) of postmortem subjects with schizophrenia (n=21) and a comparison group of individuals without a history of psychiatric illness (n=18). Our analyses revealed a significant sex by diagnosis effect, along with significant differences in GABAergic gene expression based on medication status. Analyses revealed that in male groups, the expression of GABAergic genes was generally lower in schizophrenia cases compared to the controls, with significantly lower expression levels of GABA-Aα5, GABA-Aβ1, and GABA-Aε. In females, the expression of GABAergic genes was higher in the schizophrenia cases, with significantly higher expression of the GABA-Aβ1 and GAD67 genes. Analysis of the effect of medication in the schizophrenia subjects revealed significantly higher expression of GABA-Aα1–3, GABA-Aβ2, GABA-Aγ2, and GAD67 in the medicated group compared to the unmedicated group. These data show that sex differences in the expression of GABAergic genes occur in the ACC in schizophrenia. Therefore our data support previous findings of GABAergic dysfunction in schizophrenia and emphasize the importance of considering sex in analyses of the pathophysiology of schizophrenia. Sex differences in the GABAergic regulation of ACC function may contribute to the differences observed in the symptoms of male and female patients with schizophrenia. In addition, our findings indicate that antipsychotic medications may alter GABAergic signaling in the ACC, supporting the potential of GABAergic targets for the development of novel antipsychotic medication.