Tan Tingting, Xu Zhi, Gao Chenjie, Shen Tian, Li Lei, Chen Zimu, Chen Lei, Xu Min, Chen Bingwei, Liu Jiacheng, Zhang Zhijun, Yuan Yonggui
Department of Psychosomatics and Psychiatry, School of Medicine, Zhongda Hospital, Southeast University, Nanjing, 210009, People's Republic of China.
Key Laboratory of Developmental Genes and Human Diseases, Ministry of Education, School of Medicine, Southeast University, Nanjing, 210009, People's Republic of China.
BMC Psychiatry. 2022 Mar 25;22(1):218. doi: 10.1186/s12888-022-03860-z.
Most antidepressants have been developed on the basis of the monoamine deficiency hypothesis of depression, in which neuronal serotonin (5-HT) plays a key role. 5-HT biosynthesis is regulated by the rate-limiting enzyme tryptophan hydroxylase-2 (TPH2). TPH2 methylation is correlated with antidepressant effects. Resting-state functional MRI (rs-fMRI) is applied for detecting abnormal brain functional activity in patients with different antidepressant effects. We will investigate the effect of the interaction between rs-fMRI and TPH2 DNA methylation on the early antidepressant effects.
A total of 300 patients with major depressive disorder (MDD) and 100 healthy controls (HCs) were enrolled, of which 60 patients with MDD were subjected to rs-fMRI. Antidepressant responses was assessed by a 50% reduction in 17-item Hamilton Rating Scale for Depression (HAMD-17) scores at baseline and after two weeks of medication. The RESTPlus software in MATLAB was used to analyze the rs-fMRI data. The amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), fractional ALFF (fALFF), and functional connectivity (FC) were used, and the above results were used as regions of interest (ROIs) to extract the average value of brain ROIs regions in the RESTPlus software. Generalized linear model analysis was performed to analyze the association between abnormal activity found in rs-fMRI and the effect of TPH2 DNA methylation on antidepressant responses.
Two hundred ninety-one patients with MDD and 100 HCs were included in the methylation statistical analysis, of which 57 patients were included in the further rs-fMRI analysis (3 patients were excluded due to excessive head movement). 57 patients were divided into the responder group (n = 36) and the non-responder group (n = 21). Rs-fMRI results showed that the ALFF of the left inferior frontal gyrus (IFG) was significantly different between the two groups. The results showed that TPH2-1-43 methylation interacted with ALFF of left IFG to affect the antidepressant responses (p = 0.041, false discovery rate (FDR) corrected p = 0.149).
Our study demonstrated that the differences in the ALFF of left IFG between the two groups and its association with TPH2 methylation affect short-term antidepressant drug responses.
大多数抗抑郁药是基于抑郁症的单胺缺乏假说研发的，其中神经元5-羟色胺（5-HT）起关键作用。5-HT生物合成受限速酶色氨酸羟化酶-2（TPH2）调控。TPH2甲基化与抗抑郁作用相关。静息态功能磁共振成像（rs-fMRI）用于检测不同抗抑郁效果患者的脑功能活动异常。我们将研究rs-fMRI与TPH2 DNA甲基化之间的相互作用对早期抗抑郁效果的影响。
共纳入300例重度抑郁症（MDD）患者和100例健康对照（HC），其中60例MDD患者接受rs-fMRI检查。通过基线及用药两周后17项汉密尔顿抑郁量表（HAMD-17）评分降低50%来评估抗抑郁反应。使用MATLAB中的RESTPlus软件分析rs-fMRI数据。采用低频振幅（ALFF）、局部一致性（ReHo）、分数低频振幅（fALFF）和功能连接（FC），并将上述结果作为感兴趣区（ROI），在RESTPlus软件中提取脑ROI区域的平均值。进行广义线性模型分析，以分析rs-fMRI中发现的异常活动与TPH2 DNA甲基化对抗抑郁反应的影响之间的关联。
291例MDD患者和100例HC纳入甲基化统计分析，其中57例患者纳入进一步的rs-fMRI分析（3例因头部运动过度被排除）。57例患者分为反应者组（n = 36）和无反应者组（n = 21）。rs-fMRI结果显示，两组之间左额下回（IFG）的ALFF有显著差异。结果表明，TPH2-1-43甲基化与左IFG的ALFF相互作用，影响抗抑郁反应（p = 0.041，错误发现率（FDR）校正p = 0.149）。
我们的研究表明，两组之间左IFG的ALFF差异及其与TPH2甲基化的关联影响短期抗抑郁药物反应。
