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Although previous studies reported structural changes associated with electroconvulsive therapy (ECT) in major depressive disorder (MDD), the underlying molecular basis of ECT remains largely unknown. Here, we combined two independent structural MRI datasets of MDD patients receiving ECT and transcriptomic gene expression data from Allen Human Brain Atlas to reveal the molecular basis of ECT for MDD. We performed partial least square regression to explore whether/how gray matter volume (GMV) alterations were associated with gene expression level. Functional enrichment analysis was conducted using Metascape to explore ontological pathways of the associated genes. Finally, these genes were further assigned to seven cell types to determine which cell types contribute most to the structural changes in MDD patients after ECT. We found significantly increased GMV in bilateral hippocampus in MDD patients after ECT. Transcriptome-neuroimaging association analyses showed that expression levels of 726 genes were positively correlated with the increased GMV in MDD after ECT. These genes were mainly involved in synaptic signaling, calcium ion binding and cell-cell signaling, and mostly belonged to excitatory and inhibitory neurons. Moreover, we found that the MDD risk genes of CNR1, HTR1A, MAOA, PDE1A, and SST as well as ECT related genes of BDNF, DRD2, APOE, P2RX7, and TBC1D14 showed significantly positive associations with increased GMV. Overall, our findings provide biological and molecular mechanisms underlying structural plasticity induced by ECT in MDD and the identified genes may facilitate future therapy for MDD., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Although many previous studies reported structural plasticity of the hippocampus and amygdala induced by electroconvulsive therapy (ECT) in major depressive disorder (MDD), yet the exact roles of both areas for antidepressant effects are still controversial., Methods: In the current study, segmentation of amygdala and hippocampal sub-regions was used to investigate the longitudinal changes of volume, the relationship between volume and antidepressant effects, and prediction performances for ECT in MDD patients before and after ECT using two independent datasets., Results: As a result, MDD patients showed selectively and consistently increased volume in the left lateral nucleus, right accessory basal nucleus, bilateral basal nucleus, bilateral corticoamygdaloid transition (CAT), bilateral paralaminar nucleus of the amygdala, and bilateral hippocampus-amygdala transition area (HATA) after ECT in both datasets, whereas marginally significant increase of volume in bilateral granule cell molecular layer of the head of dentate gyrus, the bilateral head of cornu ammonis (CA) 4, and left head of CA 3. Correlation analyses revealed that increased volume of left HATA was significantly associated with antidepressant effects after ECT. Moreover, volumes of HATA in the MDD patients before ECT could be served as potential biomarkers to predict ECT remission with the highest accuracy of 86.95% and 82.92% in two datasets (The predictive models were trained on Dataset 2 and the sensitivity, specificity and accuracy of Dataset 2 were obtained from leave-one-out-cross-validation. Thus, they were not independent and very likely to be inflated)., Conclusions: These results not only suggested that ECT could selectively induce structural plasticity of the amygdala and hippocampal sub-regions associated with antidepressant effects of ECT in MDD patients, but also provided potential biomarkers (especially HATA) for effectively and timely interventions for ECT in clinical applications.

An increasing number of neuroimaging studies have consistently revealed that disrupted functional interactions within the cognitive emotion regulation network (ERN) contribute to the onset of major depressive disorders (MDD). To disentangle the functional reorganization of ERN after electroconvulsive therapy (ECT) in MDD is curial for understanding its neuropathology. Resting-state functional magnetic resonance imaging data was collected from 23 MDD patients before and after ECT, as well as 25 healthy controls. Network modularity analysis was used to identify the submodules and functional connectivity (FC) was used to investigate the functional reorganization of ERN in the MDD patients after ECT. Four submodules of ERN were identified, including emotion response module (ERM), emotion integration module (EIM), emotion generation module (EGM), and emotion execution module (EEM). The increased intra-modular FC of EEM and inter-modular FCs of EEM with EIM\ERM were found in MDD patients after ECT. Modular transition analysis revealed that left ventrolateral prefrontal cortex, supplementary motor area, posterior cingulate cortex, right angular gyrus, and right precentral gyrus were transferred across different submodules across the three groups. Further analyses showed correlations between changed FC and clinical symptoms in the MDD patients after ECT. Finally, we also identified 11 increased connections between nodes belonging to different submodules of ERN in MDD patients after ECT. These results showed that ECT could induce functional reorganization of intra- and inter-modules within the ERN, and the functional changes were related to therapeutic efficacy or memory impairments of ECT in MDD patients.

Although electroconvulsive therapy (ECT) is an efficient treatment for major depressive disorder (MDD), however, it also brings memory impairment. The insula is a critical brain structure for coordinating affective, cognitive memory, saliency processing, and attention switching suggesting functional activity of insula maybe an important indicator to delineate the treatment and side effects of ECT. Here, Resting-state functional connectivity analyses of insular subregions were performed to reveal the changes of connectivity in 23 MDD patients before and after ECT and 25 healthy control (HC) and identified significantly increased functional connectivity of the right ventral anterior insular subregion with bilateral caudate, angular gyrus, and dorsolateral prefrontal cortex after ECT. Granger causality analyses identified significantly increased effective connectivity from dorsolateral prefrontal cortex to right angular gyrus in MDD patients after ECT. Furthermore, increased effective connectivity from dorsolateral prefrontal cortex to right angular gyrus exhibited significantly positive correlation with changed Hamilton Rating Scale for Depression scores. These results showed that ECT can normalize abnormal functional connectivity and effective connectivity in MDD. Our findings also indicated that the right ventral anterior insula and effective connectivity from dorsolateral prefrontal cortex to right angular gyrus are biomarkers of antidepressant effects during ECT of MDD.

Although electroconvulsive therapy (ECT) is one of the most effective treatments for major depressive disorder (MDD), the mechanism underlying the therapeutic efficacy and side effects of ECT remains poorly understood. Here, we investigated alterations in the cortical morphological measurements including cortical thickness (CT), surface area (SA), and local gyrification index (LGI) in 23 MDD patients before and after ECT. Furthermore, multivariate pattern analysis using linear support vector machine (SVM) was applied to investigate whether the changed morphological measurements can be effective indicators for therapeutic efficacy of ECT. Surface-based morphometry (SBM) analysis found significantly increased vertex-wise and regional cortical thickness (CT) and surface area (SA) in widespread regions, mainly located in the left insula (INS) and left fusiform gyrus, as well as hypergyrification in the left middle temporal gyrus (MTG) in MDD patients after ECT. Partial correlational analyses identified associations between the morphological properties and depressive symptom scores and impaired memory scores. Moreover, SVM result showed that the changed morphological measurements were effective to classify the MDD patients before and after ECT. Our findings suggested that ECT may enhance cortical neuroplasticity to facilitate neurogenesis to remit depressive symptoms and to impair delayed memory. These findings indicated that the cortical morphometry is a good index for therapeutic efficacy of ECT.

Background: Electroconvulsive therapy (ECT) has been demonstrated to be an effective treatment of major depressive disorder (MDD). However, the neuroanatomical basis of response to ECT is still largely unknown., Methods: In present study, we used functional connectivity density (FCD) and resting-state functional connectivity (RSFC) to identify the relationship between the changes of resting-state activities and ECT responses in 23 MDD patients before and after ECT. In addition, the identified neural indices as classification characteristics were entered into multivariate pattern analysis using linear support vector machine (SVM) to classify 23 MDD patients before ECT from 25 gender, age and years of education matched healthy controls., Results: We found that the changes of local FCD (lFCD), not long-range FCD, of the left pre-/postcentral gyrus (Pre-/postCG), left superior temporal gyrus (STG), and right STG were significantly correlated with the changes of Hamilton Rating Scale for Depression (HRSD) scores in MDD patients before and after ECT. The subsequent functional connectivity analysis revealed significantly decreased functional connectivity between right STG and right intraparietal sulcus (IPS) in MDD after ECT in spite of no correlation with HRSD scores. Finally, SVM-based classification achieved an accuracy of 72.92% with a sensitivity of 73.91% and a specificity of 72% by leave-one-out cross-validation., Conclusions: Our findings indicated that Pre-/postCG and bilateral STG play an important role in response of ECT in MDD patients, and the lFCD in these areas may serve as a biomarker for predicting ECT response., (Copyright © 2017 Elsevier B.V. All rights reserved.)