Xu Zhi, Tan Tingting, Jiang Yan, Tang Haiping, Chen Bingwei, Chen Wenji, Yuan Yonggui
Department of Psychosomatics and Psychiatry, Zhongda Hospital, School of Medicine, Jiangsu Provincial Key Laboratory of Brain Science and Medicine, Southeast University, Nanjing 210009, China.
Department of Psychosomatics and Psychiatry, Zhongda Hospital, School of Medicine, Jiangsu Provincial Key Laboratory of Brain Science and Medicine, Southeast University, Nanjing 210009, China; Institute of Mental Health, Suzhou Psychiatric Hospital, The Affiliated Guangji Hospital of Soochow University, Suzhou, Jiangsu 215137, China.
Brain Res Bull. 2025 Sep;229:111469. doi: 10.1016/j.brainresbull.2025.111469. Epub 2025 Jul 15.
Functional abnormalities in different brain regions are related to major depressive disorder (MDD). In our previous study, we demonstrated that DNA methylation of Tryptophan Hydroxylase-2 (TPH2) is related to the occurrence of MDD. The present study aimed to identify the interaction of the functional activities of brain regions identified as regions of interest (RoI) in MDD with TPH2 gene methylation to explore their relationship.
Data from 98 patients with MDD and 63 controls were utilized. The amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo) and fractional ALFF (fALFF), were used to identify ROIs regions in the RESTPlus Software of MATLAB. General linear regression (GLM) was performed to analyze the association between functional connectivity (FC) found in rs-fMRI and the effect of TPH2 DNA methylation in patients with MDD and controls.
In the rs-fMRI analysis, the ALFF of right superior generalized gyrus (STG) was significantly different between the MDD and HCs groups (p < 0.05). The ReHo of right Middle temporal gyrus (MTG) and left middle occipital gyrus (MOG) were significantly different between the two groups (p < 0.05). These ROIs were used to further analyze the FC differences between MDD and HCs, and it was found that the FC of right STG and right superior frontal gyrus (SFG) and the FC of right MTG and right MOG were significantly different between the two groups (p < 0.05). It was further found that the interaction between ALFF activity of the right STG and TPH2-5-203 methylation (β=-2.108, p = 0.004), ReHo activity level of the right MTG, and TPH2-5-203 methylation were correlated with the occurrence of MDD (β=-1.720, p = 0.018).
This study found that the functional activities of the temporal lobe, middle occipital gyrus, and superior frontal gyrus were abnormal in patients with MDD compared to HCs. Furthermore, the interaction of functional activities of the right superior temporal gyrus /middle temporal gyrus and TPH2 methylation were associated with the occurrence of MDD, suggesting that the combination of functional activities and DNA methylation was helpful for diagnosis of MDD.
不同脑区的功能异常与重度抑郁症（MDD）相关。在我们之前的研究中，我们证明了色氨酸羟化酶2（TPH2）的DNA甲基化与MDD的发生有关。本研究旨在确定在MDD中被确定为感兴趣区域（RoI）的脑区功能活动与TPH2基因甲基化之间的相互作用，以探索它们之间的关系。
使用了来自98例MDD患者和63名对照的数据。在MATLAB的RESTPlus软件中，使用低频振幅（ALFF）、局部一致性（ReHo）和分数低频振幅（fALFF）来确定RoI区域。进行一般线性回归（GLM）分析静息态功能磁共振成像（rs-fMRI）中发现的功能连接（FC）与MDD患者和对照中TPH2 DNA甲基化的影响之间的关联。
在rs-fMRI分析中，MDD组和健康对照组之间右上颞回（STG）的ALFF有显著差异（p<0.05）。两组之间右中颞回（MTG）和左中枕回（MOG）的ReHo有显著差异（p<0.05）。这些RoI被用于进一步分析MDD组和健康对照组之间的FC差异，发现两组之间右STG与右上额回（SFG）的FC以及右MTG与右MOG的FC有显著差异（p<0.05）。进一步发现右STG的ALFF活性与TPH2-5-203甲基化之间的相互作用（β=-2.108，p=0.004）、右MTG的ReHo活性水平以及TPH2-5-203甲基化与MDD的发生相关（β=-1.720，p=0.018）。
本研究发现，与健康对照组相比，MDD患者的颞叶、中枕回和额上回功能活动异常。此外，右上颞回/中颞回的功能活动与TPH2甲基化之间的相互作用与MDD的发生有关，表明功能活动和DNA甲基化的结合有助于MDD的诊断。
