Abstract：
The early growth response 3 (EGR3) gene is an immediate early gene that is expressed throughout the brain and has been suggested as a potential susceptibility gene for schizophrenia (SZ). EGR3 impairment is associated with various neurodevelopmental dysfunctions, and some animal studies have reported a role for EGR3 function in the prefrontal cortex. Therefore, EGR3 genotype variation may be reflected in prefrontal function. By using multi-channel near-infrared spectroscopy (NIRS) in an imaging genetics approach, we tested for an association between the EGR3 gene polymorphism and prefrontal hemodynamic response during a cognitive task in patients with SZ. We assessed 73 chronic patients with SZ and 73 age-, gender-, and genotype-matched healthy controls (HC) who provided written informed consent. We used NIRS to measure changes in prefrontal oxygenated hemoglobin concentration (oxyHb) during the letter version of a verbal fluency task (VFT). Statistical comparisons were performed among EGR3 genotype subgroups (rs35201266, GG/GA/AA). The AA genotype group showed significantly smaller oxyHb increases in the left dorsolateral prefrontal cortex (DLPFC) during the VFT than the GG and GA genotype groups; this was true for both patients with SZ and HC. Our findings provide in vivo human evidence of a significant influence of EGR3 polymorphisms on prefrontal hemodynamic activation level in healthy adults and in patients with SZ. Genetic variation in EGR3 may affect prefrontal function through neurodevelopment. This study illustrates the usefulness of NIRS in imaging genetics investigations on psychiatric disorders.
摘要：
早期生长反应3（EGR3）基因是在整个大脑中表达的即时早期基因，已被认为是精神分裂症（SZ）的潜在易感基因。EGR3损伤与各种神经发育障碍有关，一些动物研究报道了EGR3在前额叶皮层中的作用。因此,EGR3基因型变异可能反映在前额叶功能上。通过在成像遗传学方法中使用多通道近红外光谱（NIRS），我们在SZ患者的认知任务中测试了EGR3基因多态性与前额叶血流动力学反应之间的关联.我们评估了73例SZ和73岁的慢性患者，性别-,和提供书面知情同意书的基因型匹配的健康对照（HC）。我们使用NIRS来测量言语流利任务（VFT）的字母版本中前额氧合血红蛋白浓度（oxyHb）的变化。在EGR3基因型亚组(rs35201266,GG/GA/AA)之间进行统计比较。与GG和GA基因型组相比，在VFT期间，AA基因型组显示左背外侧前额叶皮层（DLPFC）的oxyHb增加明显较小；对于SZ和HC患者都是如此。我们的发现提供了体内人类证据，证明EGR3多态性对健康成年人和SZ患者的前额叶血流动力学激活水平有显着影响。EGR3的遗传变异可能通过神经发育影响前额叶功能。这项研究说明了NIRS在精神疾病的影像学遗传学研究中的有用性。
