Department of Psychiatry, Philipps-University Marburg, Rudolf-Bultmann-Str. 8, 35039 Marburg, Germany.
Neuroimage. 2010 Jan 15;49(2):1831-6. doi: 10.1016/j.neuroimage.2009.09.028. Epub 2009 Sep 23.
Recent genetic studies found the A allele of the variant rs1006737 in the alpha 1C subunit of the L-type voltage-gated calcium channel (CACNA1C) gene to be overrepresented in patients suffering from bipolar disorder, schizophrenia or major depression. While the functions underlying the pathophysiology of these psychiatric disorders are yet unknown, impaired performance in verbal fluency tasks is an often replicated finding. We investigated the influence of the rs1006737 single nucleotide polymorphism (SNP) on verbal fluency and its neural correlates.
Brain activation was measured with functional magnetic resonance imaging (fMRI) during a semantic verbal fluency task in 63 healthy male individuals. They additionally performed more demanding verbal fluency tasks outside the scanner. All subjects were genotyped for CACNA1C rs1006737.
For the behavioral measures outside the scanner, rs1006737genotype had an effect on semantic but not on lexical verbal fluency with decreased performance in risk-allele carriers. In the fMRI experiment, while there were no differences in behavioural performance, increased activation in the left inferior frontal gyrus as well as the left precuneus was found in risk-allele carriers in the semantic verbal fluency task.
The rs1006737 variant does influence language production on a semantic level in conjunction with the underlying neural systems. These findings are in line with results of studies in bipolar disorder, schizophrenia and major depression and may explain some of the cognitive and brain activation variation found in these disorders.
最近的遗传研究发现，L 型电压门控钙通道（CACNA1C）α1C 亚基变体 rs1006737 的 A 等位基因在患有双相情感障碍、精神分裂症或重度抑郁症的患者中更为常见。虽然这些精神疾病的病理生理学基础的功能尚不清楚，但言语流畅性任务表现受损是一个经常被复制的发现。我们研究了 rs1006737 单核苷酸多态性（SNP）对言语流畅性及其神经相关性的影响。
在 63 名健康男性中，使用功能磁共振成像（fMRI）测量语义言语流畅性任务期间的大脑激活。他们还在扫描仪外进行了更具挑战性的言语流畅性任务。所有受试者均进行了 CACNA1C rs1006737 基因分型。
对于扫描仪外的行为测量，rs1006737 基因型对语义但不对词汇言语流畅性有影响，风险等位基因携带者的表现下降。在 fMRI 实验中，虽然行为表现没有差异，但在语义言语流畅性任务中，风险等位基因携带者的左额下回和左楔前叶的激活增加。
rs1006737 变体确实会影响语义语言产生，同时影响潜在的神经系统。这些发现与双相情感障碍、精神分裂症和重度抑郁症的研究结果一致，并可能解释这些疾病中发现的一些认知和大脑激活变化。
