Max Planck Institute of Psychiatry, D-80804 Munich, Germany.
Neuron. 2011 Apr 28;70(2):252-65. doi: 10.1016/j.neuron.2011.04.005.
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.
重度抑郁症（MD）是最常见的精神疾病之一，也是导致工作生产力下降的主要原因。遗传和环境风险因素的结合可能导致 MD。我们提供了一项全基因组关联研究的数据，该研究揭示了神经元特异性中性氨基酸转运蛋白（SLC6A15）是 MD 的易感基因。人类的风险等位基因携带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 MD 病理生理学中的一个关键脑区。相同的多态性也与海马体体积和神经元完整性的改变有关。因此，由于遗传或环境因素导致的 SLC6A15 表达降低，可能会改变与 MD 易感性相关的神经元回路。我们从人类遗传学、表达研究、脑成像和动物模型获得的一致数据表明，MD 可能存在一种可通过药物靶向的病理生理学机制。
