Dataset Information

Electroconvulsive therapy modulates functional interactions between submodules of the emotion regulation network in major depressive disorder.

ABSTRACT: 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.

SUBMITTER: Xu J

PROVIDER: S-EPMC7406501 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Electroconvulsive therapy modulates functional interactions between submodules of the emotion regulation network in major depressive disorder.

Xu Jinping J Wei Qiang Q Bai Tongjian T Wang Lijie L Li Xuemei X He Zhengyu Z Wu Jianhuang J Hu Qingmao Q Yang Xun X Wang Chao C Tian Yanghua Y Wang Jiaojian J Wang Kai K

Translational psychiatry 20200805 1

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 h ...[more]

PMID: 32759936

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Project description:Major depressive disorder (MDD) is a complex mental disorder featured by an increased focus on the self and emotion dysregulation whose interaction remains unclear, though. At the same time, various studies observed abnormal representation of global fMRI brain activity in specifically those regions, e.g., cortical midline structure (CMS) in MDD that are associated with the self. Are the self and its impact on emotion regulation related to global brain activity unevenly represented in CMS relative to non-CMS? Addressing this yet open question is the main goal of our study. We here investigate post-acute treatment responder MDD and healthy controls in fMRI during an emotion task involving both attention and reappraisal of negative and neutral stimuli. We first demonstrate abnormal emotion regulation with increased negative emotion severity on the behavioral level. Next, focusing on a recently established three-layer topography of self, we show increased representation of global fMRI brain activity in specifically those regions mediating the mental (CMS) and exteroceptive (Right temporo-parietal junction and mPFC) self in post-acute MDD during the emotion task. Applying a complex statistical model, namely multinomial regression analyses, we show that increased global infra-slow neural activity in the regions of the mental and exteroceptive self modulates the behavioral measures of specifically negative emotion regulation (emotion attention and reappraisal/suppression). Together, we demonstrate increased representation of global brain activity in regions of the mental and exteroceptive self, including their modulation of negative emotion dysregulation in specifically the infra-slow frequency range (0.01 to 0.1 Hz) of post-acute MDD. These findings support the assumption that the global infra-slow neural basis of the increased self-focus in MDD may take on the role as basic disturbance in that it generates the abnormal regulation of negative emotions.

Project description:Background: Major Depressive Disorder (MDD) is a moderately heritable disorder with a high lifetime prevalence. At present, laboratory blood tests to support MDD diagnosis are not available. Methods: We used a classifier approach on blood gene expression profiles of a unique set of non-medicated subjects (MDD patients and controls) to select genes of which expression is predictive for disease status. To reveal blood gene expression changes related to MDD disease, we applied a powerful ex vivo stimulus to the blood, i.e. incubation with lipopolysaccharide (LPS; 10 ng/ml blood). Results: Based on LPS-stimulated blood gene expression using whole-genome microarrays in 42 subjects (primary cohort; 21 MDD patients (mean age 42.3 years), 21 healthy controls (mean age 41.9 years)), we identified a set of genes (CAPRIN1, CLEC4A, KRT23, MLC1, PLSCR1, PROK2, ZBTB16) that serves as a molecular signature of MDD. These findings were validated for the primary cohort using an independent quantitative PCR method (P = 0.007). The difference between depressive patients and controls was confirmed (P = 0.019) in a replication cohort of 13 patients with MDD (mean age 42.8 years) and 14 controls (mean age 45.6 years). The MDD-signature score comprised of expression levels of 7 genes could discriminate depressive patients from controls with sensitivity of 76.9% and specificity of 71.8%. Conclusions: We show for the first time that molecular analysis of stimulated blood cells can be used as an endophenotype for MDD diagnosis, which is a milestone in establishing biomarkers for neuropsychiatric disorders with moderate heritability in general. Our results may provide a new entry point for following and predicting treatment outcome, as well as prediction of severity and recurrence of MDD. In total, 33 MDD patients and 34 healthy controls were analyzed using basal gene expression in whole blood, and gene expression from whole blood that was stimulated with LPS for 5-6 h, using microarrays. Patients were arbitrarily selected from all patients to serve as primary cohort (nMDD = 21 (MDD01-MDD21); nControls = 21 (Con01-Con21)), or replication cohort (nMDD = 12 (MDD22-MDD35); nControls = 13 (Con22-Con37)) using microarrays. This submission does not include Samples CON21_LPS or CON30_LPS.

Dataset Information

Electroconvulsive therapy modulates functional interactions between submodules of the emotion regulation network in major depressive disorder.

Publications

Electroconvulsive therapy modulates functional interactions between submodules of the emotion regulation network in major depressive disorder.

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