Wang Lijuan, Liu Zhifen, Cao Xiaohua, Li Jianying, Zhang Aixia, Sun Ning, Yang Chunxia, Zhang Kerang
1 Department of Psychiatry, The First Hospital of Shanxi Medical University , Taiyuan, China .
2 The First Clinical Medical College, Shanxi Medical University , Taiyuan, China .
Genet Test Mol Biomarkers. 2017 Sep;21(9):523-530. doi: 10.1089/gtmb.2016.0426.
The SLC6A15 gene has been identified as a novel candidate gene for major depressive disorder (MDD). However, the mechanism underlying the effects of how the SLC6A15 gene affects functional brain activity of patients with MDD remains unknown.
In the present study, we investigated the effect of the SLC6A15 gene polymorphism, rs1545843, on resting-state brain function in MDD with the imaging genomic technology and the regional homogeneity (ReHo) method. Sixty-seven MDD patients and 44 healthy controls underwent functional magnetic resonance imaging scans and genotyping. The differences in ReHo between genotypes were initially tested using the student's t test. We then performed a 2 × 2 (genotypes × disease status) analysis of variance to identify the main effects of genotypes, disease status, and their interactions in MDD.
MDD patients with A+ genotypes showed decreased ReHo in the medial cingulum compared with MDD patients with the GG genotype. This was in contrast to normal controls with A+ genotypes who showed increased ReHo in the posterior cingulum and the frontal, temporal, and parietal lobes and decreased ReHo in the left corpus callosum, compared with controls with the GG genotypes. The main effect of disease was found in the frontal, parietal, and temporal lobes. The main effect of genotypes was found in the left corpus callosum and the frontal lobe. There was no interaction between rs1545843 genotypes and disease status. We found that the left corpus callosum ReHo was positively correlated with total scores of the Hamilton Depression Scale (HAMD) (p = 0.021), so as was the left inferior parietal gyrus ReHo with cognitive disorder (p = 0.02). In addition, the right middle temporal gyrus had a negative correlation with retardation (p = 0.049).
We observed an association between the SLC6A15 rs1545843 and resting-state brain function of the corpus callosum, cingulum and the frontal, parietal, and temporal lobes in MDD patients, which may be involved in the pathogenesis of MDD.
SLC6A15基因已被确定为重度抑郁症（MDD）的一个新的候选基因。然而，SLC6A15基因影响MDD患者大脑功能活动的潜在机制仍不清楚。
在本研究中，我们采用成像基因组技术和局部一致性（ReHo）方法，研究SLC6A15基因多态性rs1545843对MDD静息态脑功能的影响。67例MDD患者和44名健康对照者接受了功能磁共振成像扫描和基因分型。基因型之间的ReHo差异最初采用学生t检验进行检测。然后我们进行了一个2×2（基因型×疾病状态）方差分析，以确定基因型、疾病状态及其在MDD中的相互作用的主要影响。
与GG基因型的MDD患者相比，A+基因型的MDD患者在内侧扣带回的ReHo降低。这与GG基因型的正常对照者相反，A+基因型的正常对照者在后扣带回、额叶、颞叶和顶叶的ReHo增加，而在胼胝体左侧的ReHo降低。疾病的主要影响见于额叶、顶叶和颞叶。基因型的主要影响见于胼胝体左侧和额叶。rs1545843基因型与疾病状态之间没有相互作用。我们发现胼胝体左侧的ReHo与汉密尔顿抑郁量表（HAMD）总分呈正相关（p = 0.021），左下顶叶回的ReHo与认知障碍也呈正相关（p = 0.02）。此外，右颞中回与迟缓呈负相关（p = 0.049）。
我们观察到SLC6A15 rs1545843与MDD患者胼胝体、扣带回以及额叶、顶叶和颞叶的静息态脑功能之间存在关联，这可能参与了MDD的发病机制。
