Gothelf Doron, Hoeft Fumiko, Hinard Christine, Hallmayer Joachim F, Stoecker John Van Dover, Antonarakis Stylianos E, Morris Michael A, Reiss Allan L
The Behavioral Neurogenetics Center, Child Psychiatry Department, Schneider Children's Medical Center of Israel, Petah Tiqwa, Israel.
Hum Brain Mapp. 2007 Jun;28(6):533-42. doi: 10.1002/hbm.20405.
22q11.2 deletion syndrome (22q11.2DS) is a well-known genetic risk factor for schizophrenia. The catechol-O-methyltransferase (COMT) gene falls within the 22q11.2 minimal critical region of the deletion. Brain activity, as measured by functional magnetic resonance imaging (fMRI) during a Go/NoGo, response inhibition task was assessed in adolescents with 22q11.2DS (n = 13), typically developing (TD) controls (n = 14), and controls with developmental disability (DD, n = 9). Subjects with 22q11.2DS were also genotyped for the COMT Met/Val polymorphism. Groups did not differ on task performance. However, compared to both control groups, the 22q11.2DS group showed greater brain activation within left parietal regions. Comparison of brain activation between 22q11.2DS Met and Val subgroups revealed significantly increased activation (Met>Val) in the cingulate but not the dorsolateral prefrontal cortex. These preliminary findings suggest that adolescents with 22q11.2DS compensate for executive dysfunction via recruitment of parietal regions. Further, the COMT Met subgroup of 22q11.2DS may recruit additional cingulate activation for tasks requiring attention and inhibition. 22q11.2DS is a unique model for learning about the deleterious effects of decreased dosage of the COMT gene on brain function.
22q11.2缺失综合征（22q11.2DS）是一种众所周知的精神分裂症遗传风险因素。儿茶酚-O-甲基转移酶（COMT）基因位于该缺失的22q11.2最小关键区域内。通过功能磁共振成像（fMRI）在“是/否”反应抑制任务期间测量大脑活动，对患有22q11.2DS的青少年（n = 13）、发育正常（TD）的对照组（n = 14）和发育障碍（DD，n = 9）的对照组进行了评估。还对患有22q11.2DS的受试者进行了COMT Met/Val多态性基因分型。各组在任务表现上没有差异。然而，与两个对照组相比，22q11.2DS组在左顶叶区域表现出更大的大脑激活。对22q11.2DS Met和Val亚组之间的大脑激活进行比较，发现扣带回而非背外侧前额叶皮质的激活显著增加（Met>Val）。这些初步发现表明，患有22q11.2DS的青少年通过募集顶叶区域来补偿执行功能障碍。此外，22q11.2DS的COMT Met亚组可能会在需要注意力和抑制的任务中募集额外的扣带回激活。22q11.2DS是一个独特的模型，用于了解COMT基因剂量减少对脑功能的有害影响。
