Cousijn Helena, Rijpkema Mark, Qin Shaozheng, van Marle Hein J F, Franke Barbara, Hermans Erno J, van Wingen Guido, Fernández Guillén
Donders Institute for Brain, Cognition and Behavior, Radboud University Nijmegen, Nijmegen, The Netherlands.
Proc Natl Acad Sci U S A. 2010 May 25;107(21):9867-72. doi: 10.1073/pnas.1003514107. Epub 2010 May 10.
Probing gene-environment interactions that affect neural processing is crucial for understanding individual differences in behavior and disease vulnerability. Here, we tested whether the current environmental context, which affects the acute brain state, modulates genotype effects on brain function in humans. We manipulated the context by inducing acute psychological stress, which increases noradrenergic activity, and probed its effect on tonic activity and phasic responses in the amygdala using two MRI techniques: conventional blood oxygen level-dependent functional MRI and arterial spin labeling. We showed that only carriers of a common functional deletion in ADRA2B, the gene coding for the alpha2b-adrenoreceptor, displayed increased phasic amygdala responses under stress. Tonic activity, reflecting the perfusion of the amygdala, increased independently of genotype after stress induction. Thus, when tonic activity was heightened by stress, only deletion carriers showed increased amygdala responses. Our results demonstrate that genetic effects on brain operations can be state dependent, such that they only become apparent under specific, often environmentally controlled, conditions.
探究影响神经处理的基因-环境相互作用对于理解行为和疾病易感性的个体差异至关重要。在此，我们测试了当前影响急性脑状态的环境背景是否会调节人类基因型对脑功能的影响。我们通过诱导急性心理应激来操纵环境背景，急性心理应激会增加去甲肾上腺素能活性，并使用两种磁共振成像技术探究其对杏仁核的紧张性活动和相位反应的影响：传统的血氧水平依赖性功能磁共振成像和动脉自旋标记。我们发现，只有编码α2b-肾上腺素能受体的ADRA2B基因常见功能缺失的携带者在应激状态下杏仁核的相位反应增加。反映杏仁核灌注的紧张性活动在应激诱导后与基因型无关而增加。因此，当应激使紧张性活动增强时，只有缺失携带者的杏仁核反应增加。我们的结果表明，基因对脑活动的影响可能依赖于状态，以至于它们仅在特定的、通常由环境控制的条件下才会显现出来。
