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首页> 外文期刊>Neuron >The Neuronal Transporter Gene SLC6A15 Confers Risk to Major Depression.
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The Neuronal Transporter Gene SLC6A15 Confers Risk to Major Depression.

机译:神经元转运蛋白基因SLC6A15使患上严重抑郁症的风险增加。

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摘要

Major depression (MD) is one of the most prevalent psychiatric disorders and a leading cause of loss in work productivity. A combination of genetic and environmental risk factors probably contributes to MD. We present data from a genome-wide association study revealing a neuron-specific neutral amino acid transporter (SLC6A15) as a susceptibility gene for MD. Risk allele carrier status in humans and chronic stress in mice were associated with a downregulation of the expression of this gene in the hippocampus, a brain region implicated in the pathophysiology of MD. The same polymorphisms also showed associations with alterations in hippocampal volume and neuronal integrity. Thus, decreased SLC6A15 expression, due to genetic or environmental factors, might alter neuronal circuits related to the susceptibility for MD. Our convergent data from human genetics, expression studies, brain imaging, and animal models suggest a pathophysiological mechanism for MD that may be accessible to drug targeting.
机译:重度抑郁症(MD)是最普遍的精神疾病之一,也是导致工作效率下降的主要原因。遗传和环境风险因素的组合可能导致MD。我们目前来自全基因组关联研究的数据揭示了神经元特异性中性氨基酸转运蛋白(SLC6A15)作为MD的易感基因。人类的风险等位基因携带者状态和小鼠的慢性应激与该基因在海马体中的表达下调有关,海马体是与MD的病理生理有关的大脑区域。相同的多态性还显示出与海马体积和神经元完整性改变有关。因此,由于遗传或环境因素,SLC6A15表达降低可能会改变与MD易感性有关的神经元回路。我们来自人类遗传学,表达研究,脑成像和动物模型的融合数据表明,MD的病理生理机制可能可用于靶向药物。

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