Effect of selective serotonin reuptake inhibitor on prefrontal-striatal connectivity is dependent on the level of TNF-α in patients with major depressive disorder

• Published in: Psychological medicine 2019-11, Vol.49 (15), p.2608-2616
• Main Authors: Liu, Kai, Zhao, Xiaohua, Lu, Xiaobing, Zhu, Xiaoxia, Chen, Hui, Wang, Mengmeng, Yan, Weixin, Jing, Linlin, Deng, Yanjia, Yu, Lin, Wu, Huawang, Wen, Ge, Sun, Xuegang, Lv, Zhiping
• Format: Article
• Language: English
• Subjects: Antidepressants; Blood; Brain; Brain mapping; Chronic illnesses; Cortex; Cortex (temporal); Cytokines; Depressive personality disorders; Functional connectivity; Functional magnetic resonance imaging; Genomes; Inflammation; Magnetic resonance imaging; Mental depression; Mental disorders; Necrosis; Neostriatum; Neural networks; Neuroimaging; Original Articles; Prefrontal cortex; Psychotropic drugs; Resting; Seeds; Serotonin reuptake inhibitors; Serotonin uptake inhibitors; Serum; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Tumors
• ISSN: 0033-2917; 1469-8978
• DOI: 10.1017/S0033291718003616

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). 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. 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. 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.