GABA-A受体子单元基因的外周循环表达和月经周期的情感变化:一个维度,跨诊断研究
Jordan C Barone1, Raffaele Romano2, Anisha Nagpal3
1Department of Psychiatry, University of Illinois Chicago, Chicago, IL, US. Jbarone2@uic.edu.
月经周期的情感变化与GABA-A受体基因表达有关. GABRG2,GABRA5和GABRDmRNA的波动与情绪症状相关,这表明改变的GABAergic可塑性可能是这些条件的基础.
科学领域:
- 神经科学是一个神经科学.
- 遗传学 是一个遗传学.
- 精神病学是一个精神病学.
背景情况:
- 月经周期的情感变化 (MCAC),包括月经前失调障碍 (PMDD),受到卵巢激素的影响.
- 对MCAC的神经生物学机制的了解很少,其中一个假设涉及GABA-A受体 (GABAAR) 子单元失调.
- 在人类中测试这个假设是具有挑战性的.
研究的目的:
- 研究特定GABAAR子单元 (GABRD,GABRG2,GABRA5) 的外周mRNA表达与MCAC.严重程度之间的关系.
- 探索基因表达的个体差异及其周期性变化与情感症状轨迹的相关性.
主要方法:
- 在112名参与者 (具有自杀倾向和对照的精神病室门诊患者) 中分析了GABRD,GABRG2和GABRA5的外围mRNA表达.
- 收集每日影响评级和五个LH定时血液样本用于RT-PCR分析.
- 基因表达数据与MCAC严重程度和周期性症状模式的维度范围的相关性.
主要成果:
- 在中流阶段,GABRG2表达减少,复制了临床前发现.
- 平均GABRD,GABRG2和GABRA5表达的个体差异以及它们的月经前变化与症状严重程度相关.
- 在特定的子单元中,高表达/增加和低表达/减少都与循环恶化焦虑,易怒和自杀念头有关,这取决于阶段.
结论:
- 结果表明,改变的GABAergic可塑性,可能是失去了平静稳定性,可能与MCAC有关,而不是简单的基因表达水平的差异.
- 外围GABAAR基因表达需要进一步调查MCAC的潜在因果作用.
- 更稳定的子单元表达与较少周期性症状变化相关.
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