Department of Psychiatry and Psychotherapy, Philipps University Marburg, Rudolf-Bultmann-Str. 8, 35039 Marburg, Germany.
Department of Psychiatry and Psychotherapy, Philipps University Marburg, Rudolf-Bultmann-Str. 8, 35039 Marburg, Germany.
Neuroimage. 2014 Apr 1;89:256-61. doi: 10.1016/j.neuroimage.2013.11.030. Epub 2013 Nov 21.
Genome-wide association studies have identified the CACNA1C single nucleotide polymorphism (SNP) rs1006737 as one of the most consistent genetic findings as susceptibility locus for major psychiatric disorders. Furthermore, animal and genetic imaging studies have reported strong functional evidence for the association of CACNA1C with learning, memory, neural plasticity, and its association with the hippocampal formation. In the present study we investigated the impact of the CACNA1C SNP rs1006737 on the fractional anisotropy (FA) in the hippocampal formation as well as on verbal learning and memory in healthy individuals.
118 healthy individuals (72 males, 46 females, age 18-56years) initially underwent diffusion tensor imaging (DTI), 100 of them were included in the final analysis. We used Tract-Based Spatial Statistics (TBSS) to examine the impact of the CACNA1C SNP rs1006737 on the hippocampal formation as predefined region of interest (ROI). Furthermore, all participants completed the Verbal Learning and Memory Test (VLMT).
In the VLMT genotype was significantly associated with learning performance. Bonferroni corrected post-hoc tests indicated a diminished performance at the beginning of the learning curve in risk allele carriers compared to non-risk allele carriers. The TBSS ROI analysis revealed one cluster of reduced FA in risk allele carriers compared to non-risk allele carriers located in the right hippocampal formation. Moreover, an association between the initial learning performance and FA values was found.
These findings demonstrate that genetic variation in the CACNA1C SNP rs1006737 is associated with FA reduction in the hippocampal formation as well as with differences in learning performance in healthy individuals.
全基因组关联研究已经确定 CACNA1C 单核苷酸多态性（SNP）rs1006737 是最一致的遗传发现之一，是主要精神疾病的易感基因座。此外，动物和遗传成像研究报告了 CACNA1C 与学习、记忆、神经可塑性的强烈功能关联及其与海马结构的关联。在本研究中，我们调查了 CACNA1C SNP rs1006737 对海马结构各向异性分数（FA）以及对健康个体言语学习和记忆的影响。
118 名健康个体（72 名男性，46 名女性，年龄 18-56 岁）最初接受了弥散张量成像（DTI）检查，其中 100 名个体纳入最终分析。我们使用基于束流的空间统计学（TBSS）来检查 CACNA1C SNP rs1006737 对海马结构的影响，海马结构作为预先定义的感兴趣区（ROI）。此外，所有参与者都完成了言语学习和记忆测试（VLMT）。
在 VLMT 中，基因型与学习表现显著相关。经 Bonferroni 校正的事后检验表明，与非风险等位基因携带者相比，风险等位基因携带者在学习曲线的开始阶段表现出较差的学习成绩。TBSS ROI 分析显示，与非风险等位基因携带者相比，风险等位基因携带者的右侧海马结构存在 FA 值降低的一个簇。此外，还发现了初始学习成绩与 FA 值之间的关联。
这些发现表明，CACNA1C SNP rs1006737 的遗传变异与海马结构的 FA 值降低以及健康个体学习成绩的差异有关。
