Liu Xiaoyun, Hou Zhenghua, Yin Yingying, Xie Chunming, Zhang Haisan, Zhang Hongxing, Zhang Zhijun, Yuan Yonggui
Department of Psychosomatics and Psychiatry, School of Medicine, Zhongda Hospital, Southeast University, Nanjing, China.
Department of Neurology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
Front Psychiatry. 2020 Dec 22;11:591407. doi: 10.3389/fpsyt.2020.591407. eCollection 2020.
This study aimed to examine the interactive effects of dopamine (DA) pathway gene and disease on spontaneous brain activity and further to explore the relationship between spontaneous brain activity and the early antidepressant therapeutic effect in patients with major depressive disorder (MDD). A total of 104 patients with MDD and 64 healthy controls (HCs) were recruited. The Hamilton Depression Scale-24 (HAMD-24) was used to measure the depression severity. Both groups were given resting-state functional magnetic resonance imaging (rs-fMRI) scan. The amplitude of low-frequency fluctuation (ALFF) was calculated to reflect the spontaneous brain activity based on the rs-fMRI data. After treatment for 2 weeks, depression severity was evaluated again, and HAMD-24 reductive rate was used to measure the therapeutic effect of antidepressants. Multilocus genetic profile scores (MGPS) were used to assess the multi-site cumulative effect of DA pathway gene. The interactive effects of MDD and DA pathway gene on the ALFF of regional brain areas were measured by the multivariate linear regression analysis. Finally, partial correlation analysis (age, sex, education, and illness durations as covariates) was performed to identify the relationship between regional ALFF and therapeutic effect. MDD and DA-MGPS had interactive effects on the left fusiform gyrus (FG_L), right calcarine sulcus (CS_R), left superior temporal gyrus (STG_L), bilateral cerebellum posterior lobe (CPL), bilateral inferior frontal gyrus (IFG), and bilateral superior frontal gyrus (SFG). Partial correlation analysis revealed that the ALFF of STG_L had a significant negative correlation with 2-week HAMD-24 reductive rate ( = -0.211, = 0.035). The spontaneous activity of STG_L may be a potential biomarker of antidepressant-related early therapeutic effect underlying the influence of DA pathway genes in MDD.
本研究旨在探讨多巴胺（DA）通路基因与疾病对自发脑活动的交互作用，并进一步探索重度抑郁症（MDD）患者自发脑活动与早期抗抑郁治疗效果之间的关系。共招募了104例MDD患者和64名健康对照（HCs）。采用汉密尔顿抑郁量表24项版（HAMD - 24）来测量抑郁严重程度。两组均接受静息态功能磁共振成像（rs - fMRI）扫描。基于rs - fMRI数据计算低频振幅（ALFF）以反映自发脑活动。治疗2周后，再次评估抑郁严重程度，并使用HAMD - 24减分率来衡量抗抑郁药的治疗效果。多基因座遗传谱评分（MGPS）用于评估DA通路基因的多位点累积效应。通过多元线性回归分析测量MDD和DA通路基因对脑区ALFF的交互作用。最后，进行偏相关分析（以年龄、性别、教育程度和病程作为协变量）以确定局部ALFF与治疗效果之间的关系。MDD和DA - MGPS对左侧梭状回（FG_L）、右侧距状沟（CS_R）、左侧颞上回（STG_L）、双侧小脑后叶（CPL）、双侧额下回（IFG）和双侧额上回（SFG）的ALFF有交互作用。偏相关分析显示，STG_L的ALFF与2周HAMD - 24减分率呈显著负相关（ = -0.211， = 0.035）。在MDD中，受DA通路基因影响，STG_L的自发活动可能是抗抑郁相关早期治疗效果的潜在生物标志物。
