Genetic effects on white matter integrity in drug-naive patients with major depressive disorder: a diffusion tensor imaging study of 17 genetic loci associated with depressive symptoms
Genetic effects on white matter integrity in drug-naive patients with major depressive disorder: a diffusion tensor imaging study of 17 genetic loci associated with depressive symptoms
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DOI：
10.2147/ndt.s190268
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发表时间：
2019-01
影响因子：
3.2
通讯作者：
S. Kakeda;Keita Watanabe;A. Katsuki;K. Sugimoto;I. Ueda;Natsuki Igata;T. Kishi;N. Iwata;O. Abe;R. Yoshimura;Y. Korogi
中科院分区：
文献类型：
--
作者：
S. Kakeda;Keita Watanabe;A. Katsuki;K. Sugimoto;I. Ueda;Natsuki Igata;T. Kishi;N. Iwata;O. Abe;R. Yoshimura;Y. Korogi
背景
一项利用海量数据进行的全基因组关联研究在重性抑郁症（MDD）的候选基因中确定了17个单核苷酸多态性（SNP）。这些MDD易感性多态性可能影响白质（WM）的完整性。本研究旨在利用基于纤维束的空间统计（TBSS）方法，研究未用药的首发MDD患者的WM改变与MDD候选基因中的17个SNP之间的关系。
方法
35例未用药的首发MDD患者和47例年龄及性别匹配的健康受试者接受了扩散张量成像扫描和基因分型。针对17个SNP，利用TBSS评估了与WM完整性相关的基因型 - 诊断相互作用。
结果
对于丘脑前辐射、扣带束、皮质脊髓束、额枕下束、下纵束、上纵束、钩束、大钳和小钳，仅在精氨酸 - 谷氨酸二肽（RE）重复序列（RERE）基因中的一个SNP（rs301806）上，诊断组之间的基因型效应存在显著差异（P<0.05，经家族误差校正）。
结论
RERE多态性与首发且未用药的MDD患者的WM改变有关，这可能至少部分与MDD的表现相关。未来需要研究探索个体WM完整性方面的基因 - 环境相互作用。
Background A genome-wide association study using megadata identified 17 single-nucleotide polymorphisms (SNPs) in candidate genes for major depressive disorder (MDD). These MDD susceptibility polymorphisms may affect white matter (WM) integrity. This study aimed to investigate the relationship between WM alterations and 17 SNPs in candidate genes for MDD in the first depressive episode of drug-naive MDD patients using a tract-based spatial statistics (TBSS) method. Methods Thirty-five drug-naive MDD patients with a first depressive episode and 47 age-and sex-matched healthy subjects underwent diffusion tensor imaging scans and genotyping. The genotype–diagnosis interactions related to WM integrity were evaluated using TBSS for the 17 SNPs. Results For the anterior thalamic radiation, cingulum, corticospinal tract, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, superior longitudinal fasciculus, uncinate fasciculus, forceps major, and forceps minor, the genotype effect significantly differed between diagnosis groups (P<0.05, family-wise error corrected) in only one SNP, rs301806, in the arginine–glutamic acid dipeptide (RE) repeats (RERE) gene. Conclusion The RERE polymorphism was associated with WM alterations in first-episode and drug-naive MDD patients, which may be at least partially related to the manifestation of MDD. Future studies are needed to explore the gene–environment interactions with regard to individual WM integrity.