Choi Sunyoung, Han Kyu-Man, Kang June, Won Eunsoo, Chang Hun Soo, Tae Woo Suk, Son Kyu Ri, Kim Su-Jin, Lee Min-Soo, Ham Byung-Joo
Department of Brain and Cognitive Engineering, Korea University, Seoul, Republic of Korea.
Department of Psychiatry, Korea University College of Medicine, Seoul, Republic of Korea.
PLoS One. 2016 Oct 10;11(10):e0164301. doi: 10.1371/journal.pone.0164301. eCollection 2016.
The SLC6A15 gene has been identified as a novel candidate gene for major depressive disorder (MDD). It is presumed to be involved in the pathophysiology of MDD through regulation of glutamate transmission in the brain. However, the involvement of this gene in microstructural changes in white matter (WM) tracts remains unclear. We aimed to investigate the influence of a polymorphism of this gene (rs1545853) on the structural integrity of WM tracts in the cortico-limbic network.
Eighty-six patients with MDD and 64 healthy controls underwent T1-weighted structural magnetic resonance imaging, including diffusion tensor imaging (DTI), and genotype analysis. We selected the genu of the corpus callosum, the uncinate fasciculus, cingulum, and fornix as regions of interest, and extracted fractional anisotropy (FA) values using the FMRIB Diffusion Toolbox software.
FA values for the left parahippocampal cingulum (PHC) was significantly reduced in the patients with MDD compared to healthy control participants (p = 0.004). We also found that MDD patients with the A allele showed reduced FA values for the left PHC than did healthy controls with the A allele (p = 0.012). There was no significant difference in the FA value of left PHC for the comparison between the G homozygotes of MDD and healthy control group.
We observed an association between the risk allele of the SLC6A15 gene rs1545843 and the WM integrity of the PHC in MDD patients, which is known to play an important role in the neural circuit involved in emotion processing.
溶质载体家族6成员15（SLC6A15）基因已被确定为重度抑郁症（MDD）的一个新候选基因。据推测，它通过调节大脑中的谷氨酸传递参与MDD的病理生理过程。然而，该基因在白质（WM）束微观结构变化中的作用仍不清楚。我们旨在研究该基因的一个多态性（rs1545853）对皮质-边缘网络中WM束结构完整性的影响。
86例MDD患者和64名健康对照者接受了T1加权结构磁共振成像，包括扩散张量成像（DTI）和基因分型分析。我们选择胼胝体膝部、钩束、扣带束和穹窿作为感兴趣区域，并使用FMRIB扩散工具箱软件提取分数各向异性（FA）值。
与健康对照者相比，MDD患者左侧海马旁扣带束（PHC）的FA值显著降低（p = 0.004）。我们还发现，携带A等位基因的MDD患者左侧PHC的FA值低于携带A等位基因的健康对照者（p = 0.012）。MDD的G纯合子与健康对照组之间左侧PHC的FA值比较无显著差异。
我们观察到SLC6A15基因rs1545843的风险等位基因与MDD患者PHC的WM完整性之间存在关联，已知PHC在参与情绪处理的神经回路中起重要作用。
