PNAS:为什么焦虑在青春期达到顶峰
美国康奈尔大学一项研究发现，一个影响内源性大麻素信号传导的常见的基因突变改变了大脑回路的发育，这可能对青春期的焦虑相关行为的出现有贡献。已知青春期的焦虑障碍的发生率高，但是许多治疗是基于对成年人的研究。理解遗传因素如何影响大脑发育的不同阶段出现精神障碍的风险，对于优化治疗是关键。BJ Casey及其同事研究了一个影响内源性大麻素信号传导的常见的遗传突变如何改变了前额边缘回路的发育，这可能对青春期的焦虑相关行为的出现有贡献。这组作者使用弥散磁共振成像测量了1050名3到21岁的个体的前额叶皮层与边缘结构之间的连通性。一些受试者由于一种干扰了脂肪酰胺水解酶(FAAH)的活性的遗传突变而有更高的内源性大麻素水平，脂肪酰胺水解酶(FAAH)能分解内源性大麻素。与没有这个脂肪酰胺水解酶(FAAH)突变等位基因的个体相比，那些具有这个等位基因的个体表现出了更高的前额边缘连通性以及更低的自我报告的焦虑，但是只是在12岁之后才是如此。这些发现表明了这个遗传因子对大脑回路以及青春期焦虑相关行为的出现的效应。这组作者说，这些结果可能帮助开发焦虑的生物标记，以及开发精确的医学方法，优化对患精神障碍的青少年的治疗。
原文链接：
Individual differences in frontolimbic circuitry and anxiety emerge with adolescent changes in endocannabinoid signaling across species
原文摘要：
Anxiety disorders peak in incidence during adolescence, a developmental window that is marked by dynamic changes in GENE expression, endocannabinoid signaling, and frontolimbic circuitry. We tested whether genetic alterations in endocannabinoid signaling related to a common polymorphism in fatty acid amide hydrolase (FAAH), which alters endocannabinoid anandamide (AEA) levels, would impact the development of frontolimbic circuitry implicated in anxiety disorders. In a pediatric imaging sample of over 1,000 3- to 21-y-olds, we show effects of the FAAH genotype specific to frontolimbic connectivity that emerge by ∼12 y of age and are paralleled by changes in anxiety-related behavior. Using a knock-in mouse model of the FAAH polymorphism that controls for genetic and environmental backgrounds, we confirm phenotypic differences in frontoamygdala circuitry and anxiety-related behavior by postnatal day 45 (P45), when AEA levels begin to decrease, and also, at P75 but not before. These results, which converge across species and level of analysis, highlight the importance of underlying developmental neurobiology in the emergence of genetic effects on brain circuitry and function. Moreover, the results have important implications for the identification of risk for disease and precise targeting of treatments to the biological state of the developing brain as a function of developmental changes in gene expression and neural circuit maturation.
作者：Dylan G. Gee
