Department of Psychology, Institute of Psychiatry, King's College London, London, United Kingdom.
Hum Brain Mapp. 2009 Dec;30(12):3934-43. doi: 10.1002/hbm.20818.
The majority of psychopathology is rooted early in life and first emerges during childhood and adolescence. However, little is known about how risk genes affect brain function to increase biological vulnerability to psychopathology in childhood, because most imaging genetic studies published so far have been conducted on adult participants. We examined the impact of neuregulin1 (NRG1), a probable susceptibility gene for schizophrenia and bipolar disorder, on brain function in a sample of 102 ten- to twelve-year-old children. Each participant performed a Go/Nogo task, whereas brain responses were measured using functional magnetic resonance imaging. Statistical parametric mapping was used to estimate the impact of genetic variation in NRG1 on brain activation. Response accuracy and reaction times did not differ as a function of NRG1 genotype. However, individuals with the high-risk variant expressed greater brain activation for both Go and Nogo stimuli in the right posterior orbital gyrus, where NRG1 genotype accounted for 11% of interindividual variance. There were no regions showing a significant interaction between NRG1 genotype and stimulus type even at trend level, suggesting that the impact of NRG1 on brain activation was not specific to either response inhibition or motor execution. These results suggest that that genetic variation in NRG1 is associated with different levels of prefrontal engagement in children as young as 10-12 years of age. Our investigation provides support to the idea that genetic factors may affect brain function to moderate vulnerability to psychopathology from childhood.
大多数精神病理学都源于生命早期，最早出现在儿童和青少年时期。然而，人们对风险基因如何影响大脑功能，从而增加儿童时期精神病理学的生物学易感性知之甚少，因为迄今为止发表的大多数影像学遗传研究都是在成年参与者中进行的。我们研究了神经调节蛋白 1（NRG1）对 102 名 10 至 12 岁儿童样本大脑功能的影响。每个参与者都执行了 Go/Nogo 任务，而大脑反应则通过功能磁共振成像进行测量。统计参数映射用于估计 NRG1 基因变异对大脑激活的影响。遗传变异与大脑激活之间的关系与反应准确性和反应时间无关。然而，高风险变异个体在右眶后回对 Go 和 Nogo 刺激的大脑激活更强，NRG1 基因型解释了个体间变异的 11%。即使在趋势水平上，也没有发现 NRG1 基因型与刺激类型之间存在显著相互作用的区域，这表明 NRG1 对大脑激活的影响不是针对反应抑制或运动执行的。这些结果表明，NRG1 的遗传变异与儿童大脑额叶参与程度的不同有关。我们的研究结果为遗传因素可能通过影响大脑功能来调节儿童时期精神病理学易感性的观点提供了支持。
