Kai Liu1,2, Xiaohua Zhao1, Xiaobing Lu3, Xiaoxia Zhu1, Hui Chen2, Mengmeng Wang1, Weixin Yan1, Linlin Jing4, Yanjia Deng2, Lin Yu3, Huawang Wu3, Ge Wen2, Xuegang Sun1,5, Zhiping Lv1. 1. School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China. 2. Medical Imaging Department, Nanfang Hospital, Southern Medical University, Guangzhou, China. 3. The Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou, China. 4. TCM Integrated Hospital of Southern Medical University, Southern Medical University, Guangzhou, China. 5. Key Laboratory of Ministry of Education for TCM Viscera-State Theory and Applications, Liaoning University of Traditional Chinese Medicine, Shenyang, China.
Abstract
BACKGROUND: We hypothesize that the tumor necrosis factor-α (TNF-α) may play a role in disturbing the effect of selective serotonin reuptake inhibitor (SSRI) on the striatal connectivity in patients with major depressive disorder (MDD). METHODS: We performed a longitudinal observation by combining resting-state functional magnetic resonance imaging (rs-fMRI) and biochemical analyses to identify the abnormal striatal connectivity in MDD patients, and to evaluate the effect of TNF-α level on these abnormal connectivities during SSRI treatment. Eighty-five rs-fMRI scans were collected from 25 MDD patients and 35 healthy controls, and the scans were repeated for all the patients before and after a 6-week SSRI treatment. Whole-brain voxel-wise functional connectivity (FC) was calculated by correlating the rs-fMRI time courses between each voxel and the striatal seeds (i.e. spherical regions placed at the striatums). The level of TNF-α in serum was evaluated by Milliplex assay. Factorial analysis was performed to assess the interaction effects of 'TNF-α × treatment' in the regions with between-group FC difference. RESULTS: Compared with controls, MDD patients showed significantly higher striatal FC in the medial prefrontal cortex (MPFC) and bilateral middle/superior temporal cortices before SSRI treatment (p < 0.001, uncorrected). Moreover, a significant interaction effect of 'TNF-α × treatment' was found in MPFC-striatum FC in MDD patients (p = 0.002), and the significance remained after adjusted for age, gender, head motion, and episode of disease. CONCLUSION: These findings provide evidence that treatment-related brain connectivity change is dependent on the TNF-α level in MDD patients, and the MPFC-striatum connectivities possibly serve as an important target in the brain.
BACKGROUND: We hypothesize that the tumor necrosis factor-α (TNF-α) may play a role in disturbing the effect of selective serotonin reuptake inhibitor (SSRI) on the striatal connectivity in patients with major depressive disorder (MDD). METHODS: We performed a longitudinal observation by combining resting-state functional magnetic resonance imaging (rs-fMRI) and biochemical analyses to identify the abnormal striatal connectivity in MDDpatients, and to evaluate the effect of TNF-α level on these abnormal connectivities during SSRI treatment. Eighty-five rs-fMRI scans were collected from 25 MDDpatients and 35 healthy controls, and the scans were repeated for all the patients before and after a 6-week SSRI treatment. Whole-brain voxel-wise functional connectivity (FC) was calculated by correlating the rs-fMRI time courses between each voxel and the striatal seeds (i.e. spherical regions placed at the striatums). The level of TNF-α in serum was evaluated by Milliplex assay. Factorial analysis was performed to assess the interaction effects of 'TNF-α × treatment' in the regions with between-group FC difference. RESULTS: Compared with controls, MDDpatients showed significantly higher striatal FC in the medial prefrontal cortex (MPFC) and bilateral middle/superior temporal cortices before SSRI treatment (p < 0.001, uncorrected). Moreover, a significant interaction effect of 'TNF-α × treatment' was found in MPFC-striatum FC in MDDpatients (p = 0.002), and the significance remained after adjusted for age, gender, head motion, and episode of disease. CONCLUSION: These findings provide evidence that treatment-related brain connectivity change is dependent on the TNF-α level in MDDpatients, and the MPFC-striatum connectivities possibly serve as an important target in the brain.
Authors: C E Millett; J Harder; J J Locascio; M Shanahan; G Santone; R N Fichorova; A Corrigan; C Baecher-Allan; K E Burdick Journal: Brain Behav Immun Date: 2020-04-06 Impact factor: 7.217