Task-Related Neural Activation Abnormalities in Patients with Remitted Major Depressive Disorder: A Coordinate-Based Meta-Analysis

Background: Major depressive disorder (MDD) is one of the most common and debilitating mental diseases; compared with healthy controls (HCs), patients with MDD still demonstrate abnormalities in brain function after complete remission. Many task-related functional magnetic resonance imaging (fMRI) studies have focused on changes in brain function in individuals with remitted MDD (rMDD), but the findings have been inconsistent. Methods: We performed meta-analysis of task-related whole-brain fMRI using anisotropic effect-size signed differential mapping software to explore differences in brain activation between rMDD patients and HCs. Meta-regression analyses were also conducted based on simple linear regression models for assessing the influence of age, sex and severity of depressive symptoms. Findings: Our meta-analysis included 13 studies and 18 experiments comprising observations from 304 rMDD patients and 321 HCs. Patients with rMDD showed increased neural activation in the left inferior parietal (peak coordinates: x = -40, y = -44, z = 48; cluster size, 101) and right fusiform gyrus (peak coordinates: x = 42, y = -28, z = -18; cluster size, 40) and decreased neural activation in the left superior frontal gyrus (peak coordinates: x = -2, y = 52, z = 8; cluster size, 2059), right middle temporal gyrus (peak coordinates: x = 50, y = -64, z = 12; cluster size, 145) and right Heschl gyrus (peak coordinates: x = 58, y = -10, z = 8; cluster size, 11). Meta-regression analysis revealed that mean age was negatively associated with brain activity in the left superior frontal gyrus (peak coordinates: x = -2, y = 52, z = 8; SDM + 0.013 per 1 point decrease in mean age, p = 0.0045). Interpretation: Our findings suggested that rMDD patients’ brain function was abnormal, especially in areas involving cognitive function, emotion regulation and perception, thus indicating that these brain regions are involved in the inherent neurophysiological mechanism of MDD and providing potential neuroimaging targets for early screening of MDD in the population. Funding Information: This study was financially supported by the National Science Foundation of China (Grant No. 82171513); Institutional Research Fund from Sichuan University (No. 2022SCUH0026); Med-X Center for Informatics funding project (No. YGJC012); 1·3·5 project for disciplines of excellence, West China Hospital, Sichuan University (No. ZYJC21069) to Dr. H.Z and research grants from Science and Technology Department of Sichuan Province (2021YJC0440); the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (2019PT310020); the National Key Research and Development Plan (grant number 2017YFC0113907) to Dr. Zhili Zou. Declaration of Interests: The authors have no conflict of interest to declare.