Li Zhuoqing, He Bo, Xu Jian, Dai Nan, Ping Liangliang, Zhou Cong, Shen Zonglin, Xu Xiufeng, Cheng Yuqi
Department of Psychiatry, First Affiliated Hospital of Kunming Medical University, Kunming, China.
Department of Medical Imaging, First Affiliated Hospital of Kunming Medical University, Kunming, China.
Front Psychiatry. 2020 Dec 7;11:531959. doi: 10.3389/fpsyt.2020.531959. eCollection 2020.
5,10-Methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism is considered as a predisposition and promising genetic candidate to major depressive disorder (MDD), as it is associated with impaired one-carbon cycles, which may be involved in the pathogenesis of depression. Cortical thickness (CT) and subcortical structure volumes have been extensively studied in MDD and have been proposed as one of the phenotypes for MDD. We intend to discuss the association between CT, subcortical structure volume, and C677T polymorphism in first-episode, treatment-naive patients with MDD. In this study, 127 adult patients with MDD and 101 age- and gender-matched healthy controls (HCs) were included. All subjects underwent T1-weighted MRI, C677T genotyping, and FreeSurfer software-based morphological analysis. MDD patients have been detected to have significantly decreased volumes in the left nucleus accumbens ( < 0.001). The 677 T allele carriers manifested with thinner CT in the left caudal anterior cingulate cortex (cACC, = 0.009) compared with CC genotype. There were significant genotype-by-diagnosis interactions for the CT in the left cACC ( = 0.009), isthmus cingulate ( = 0.002), medial orbitofrontal lobe ( = 0.012), posterior cingulate ( = 0.030), and the right lateral orbitofrontal lobe ( = 0.012). We also found a trend in the interaction effect on the volume of the left putamen ( = 0.050). Our results revealed that C677T polymorphism may be involved in the dysfunction of limbic-cortical-striatal-pallidal-thalamic (LCSPT) circuits mediating emotion processing, which may contribute to pathogenesis of MDD.
5,10-亚甲基四氢叶酸还原酶（MTHFR）基因C677T多态性被认为是重度抑郁症（MDD）的一个易患因素及有前景的遗传候选因素，因为它与一碳循环受损有关，而一碳循环可能参与了抑郁症的发病机制。在MDD中，皮质厚度（CT）和皮质下结构体积已得到广泛研究，并被认为是MDD的表型之一。我们旨在探讨首发、未接受过治疗的MDD患者的CT、皮质下结构体积与C677T多态性之间的关联。本研究纳入了127例成年MDD患者和101例年龄及性别匹配的健康对照（HCs）。所有受试者均接受了T1加权磁共振成像、C677T基因分型以及基于FreeSurfer软件的形态学分析。已检测出MDD患者左侧伏隔核体积显著减小（<0.001）。与CC基因型相比，677T等位基因携带者左侧尾侧前扣带回皮质（cACC，=0.009）的CT更薄。在左侧cACC（=0.009）、扣带回峡部（=0.002）、内侧眶额叶（=0.012）、后扣带回（=0.030）和右侧外侧眶额叶（=0.012），CT存在显著的基因型与诊断的交互作用。我们还发现左侧壳核体积的交互作用效应有一个趋势（=0.050）。我们的结果表明，C677T多态性可能参与了介导情绪加工的边缘-皮质-纹状体-苍白球-丘脑（LCSPT）回路的功能障碍，这可能有助于MDD的发病机制。
