The University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, Scotland, UK.
Psychiatry Res. 2011 Apr 30;192(1):20-8. doi: 10.1016/j.pscychresns.2011.01.015. Epub 2011 Mar 3.
Three risk variants (rs1538979, rs821577, and rs821633) in the Disrupted-in-Schizophrenia-1 (DISC1) gene have previously been associated with both schizophrenia and bipolar disorder in a recent collaborative analysis of European cohorts. In this study we examined the effects of these risk variants on brain activation during functional magnetic resonance imaging (fMRI) of the Hayling Sentence Completion Task (HSCT) in healthy volunteers (n=33), patients with schizophrenia (n=20) and patients with bipolar disorder (n=36). In the healthy controls the risk associated allele carriers of SNPs rs1538979 and rs821633 demonstrated decreased activation of the cuneus. Moreover, there was an effect of SNP rs1538979 in the pre/postcentral gyrus with decreased activation in healthy controls and increased activation in patients with schizophrenia. In the bipolar group there was decreased activation in the risk carriers of SNP rs821633 in the inferior parietal lobule and left cingulate cortex. Clusters in the precentral gyrus, left middle temporal gyrus and left cerebellum were found to be significant on examining the group × genotype interactions. These findings may provide a better understanding of the neural effects of DISC1 variants and on the pathophysiology of schizophrenia and bipolar disorder.
三个风险变异体(rs1538979、rs821577 和 rs821633)在精神分裂症相关基因 1(DISC1)中，先前在最近的欧洲队列合作分析中与精神分裂症和双相情感障碍都有关联。在这项研究中，我们在健康志愿者(n=33)、精神分裂症患者(n=20)和双相情感障碍患者(n=36)的功能磁共振成像(fMRI)的 Hayling 句子完成任务(HSCT)中检查了这些风险变异体对大脑激活的影响。在健康对照组中，SNP rs1538979 和 rs821633 的风险相关等位基因携带者表现出楔前叶和中央后回的激活减少。此外，SNP rs1538979 在后中央回也有影响，健康对照组中激活减少，精神分裂症患者中激活增加。在双相组中，SNP rs821633 的风险携带者在下顶叶和左扣带回皮层的激活减少。在检查组×基因型相互作用时，发现中央前回、左颞中回和左小脑的聚类具有显著性。这些发现可能提供了对 DISC1 变异体的神经影响的更好理解，并对精神分裂症和双相情感障碍的病理生理学有更好的理解。
