Nature子刊：发现影响抑郁的遗传因素

日前，瑞典卡罗琳医学院的一项最新研究发现，一种特定的酶是影响抑郁和焦虑的遗传因素。这将成为研发人类抗抑郁症和焦虑症药物的突破口。相关研究论文刊登在了近期出版的自然子刊《Molecular Psychiatry》上。

此前曾有研究显示，人若缺乏 CYP2C19 酶，患抑郁症和焦虑症的可能性就会降低。科学家一直在寻找导致人对抑郁症和焦虑症反应不同的遗传因素。由于这种酶会发生基因突变，因此不同人携带的 CYP2C19 酶含量也不同。

在这项最新研究中，研究人员将人类的 CYP2C19 酶注射到实验鼠的 DNA 中，随后观察这些实验鼠后代的脑部活动和行为变化。

结果显示，在胚胎阶段这些实验鼠后代大脑中就会存在这种酶，其胚胎发育与普通实验鼠相比也有所不同。

这些实验鼠后代在成年后，其脑部的海马体小于普通实验鼠。行为测试表明，它们变得焦虑，更容易受到压力的影响。海马体在大脑中控制着学习和记忆功能，还控制着个体对压力的反应以及对情绪的控制。若海马体功能失调，将可能导致抑郁症和焦虑症。（转化医学网360zhyx.com）



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Decreased hippocampal volume and increased anxiety in a transgenic mouse model expressing the human CYP2C19 gene

Selective serotonin reuptake inhibitors, tricyclic antidepressants, various psychoactive drugs, as well as endogenous steroids and cannabinoid-like compounds are metabolized by the polymorphic cytochrome P450 2C19 (CYP2C19). Absence of this enzyme has been recently shown to associate with lower levels of depressive symptoms in human subjects. To investigate endogenous functions of CYP2C19 and its potential role in brain function, we have used a transgenic mouse model carrying the human CYP2C19 gene. Here, CYP2C19 was expressed in the developing fetal, but not adult brain and was associated with altered fetal brain morphology, where mice homozygous for the CYP2C19 transgenic insert had severely underdeveloped hippocampus and complete callosal agenesis and high neonatal lethality. CYP2C19 expression was also found in human fetal brain. In adult hemizygous mice we observed besides decreased hippocampal volume, an altered neuronal composition in the hippocampal dentate gyrus. Reduced hippocampal volumes have been reported in several psychiatric disorders, supporting the relevance of this model. Here we found that adult hemizygous CYP2C19 transgenic mice demonstrate behavior indicative of increased stress and anxiety based on four different tests. We hypothesize that expression of the CYP2C19 enzyme prenatally may affect brain development by metabolizing endogenous compounds influencing this development. Furthermore, CYP2C19 polymorphism may have a role in interindividual susceptibility for psychiatric disorders.

来源：bio360