Dataset Information

Aberrant degree centrality profiles during rumination in major depressive disorder.

ABSTRACT: Rumination is closely linked to the onset and maintenance of major depressive disorder (MDD). Prior neuroimaging studies have identified the association between self-reported rumination trait and the functional coupling among a network of brain regions using resting-state functional magnetic resonance imaging (MRI). However, little is known about the underlying neural circuitry mechanism during active rumination in MDD. Degree centrality (DC) is a simple metric to denote network integration, which is critical for higher-order psychological processes such as rumination. During an MRI scan, individuals with MDD (N = 45) and healthy controls (HC, N = 46) completed a rumination state task. We examined the interaction effect between the group (MDD vs. HC) and condition (rumination vs. distraction) on vertex-wise DC. We further characterized the identified brain region's functional involvement with Neurosynth and BrainMap. Network-wise seed-based functional connectivity (FC) analysis was also conducted for the identified region of interest. Finally, exploratory correlation analysis was conducted between the identified region of interest's network FCs and self-reported in-scanner affect levels. We found that a left superior frontal gyrus (SFG) region, generally overlapped with the frontal eye field, showed a significant interaction effect. Further analysis revealed its involvement with executive functions. FCs between this region, the frontoparietal, and the dorsal attention network (DAN) also showed significant interaction effects. Furthermore, its FC to DAN during distraction showed a marginally significant negative association with in-scanner affect level at the baseline. Our results implicated an essential role of the left SFG in the rumination's underlying neural circuitry mechanism in MDD and provided novel evidence for the conceptualization of rumination in terms of impaired executive control.

SUBMITTER: Jia FN

PROVIDER: S-EPMC10619375 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Aberrant degree centrality profiles during rumination in major depressive disorder.

Jia Feng-Nan FN Chen Xiao X Du Xiang-Dong XD Tang Zhen Z Ma Xiao-Yun XY Ning Tian-Tian TT Zou Si-Yun SY Zuo Shang-Fu SF Li Hui-Xian HX Cui Shi-Xian SX Deng Zhao-Yu ZY Fu Jia-Lin JL Fu Xiao-Qian XQ Huang Yue-Xiang YX Li Xue-Ying XY Lian Tao T Liao Yi-Fan YF Liu Li-Li LL Lu Bin B Wang Yan Y Wang Yu-Wei YW Wang Zi-Han ZH Ye Gang G Zhang Xin-Zhu XZ Zhu Hong-Liang HL Quan Chuan-Sheng CS Sun Hong-Yan HY Yan Chao-Gan CG Liu Yan-Song YS

Human brain mapping 20231014 17

Rumination is closely linked to the onset and maintenance of major depressive disorder (MDD). Prior neuroimaging studies have identified the association between self-reported rumination trait and the functional coupling among a network of brain regions using resting-state functional magnetic resonance imaging (MRI). However, little is known about the underlying neural circuitry mechanism during active rumination in MDD. Degree centrality (DC) is a simple metric to denote network integration, whi ...[more]

PMID: 37837649

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Project description:BackgroundAs one of the most common diseases, major depressive disorder (MDD) has a significant adverse impact on the li of patients. As a mild form of depression, subclinical depression (SD) serves as an indicator of progression to MDD. This study analyzed the degree centrality (DC) for MDD, SD, and healthy control (HC) groups and identified the brain regions with DC alterations.MethodsThe experimental data were composed of resting-state functional magnetic resonance imaging (rs-fMRI) from 40 HCs, 40 MDD subjects, and 34 SD subjects. After conducting a one-way analysis of variance, two-sample t-tests were used for further analysis to explore the brain regions with changed DC. Receiver operating characteristic (ROC) curve analysis of single index and composite index features was performed to analyze the distinguishable ability of important brain regions.ResultsFor the comparison of MDD vs. HC, increased DC was found in the right superior temporal gyrus (STG) and right inferior parietal lobule (IPL) in the MDD group. For SD vs. HC, the SD group showed a higher DC in the right STG and the right middle temporal gyrus (MTG), and a smaller DC in the left IPL. For MDD vs. SD, increased DC in the right middle frontal gyrus (MFG), right IPL, and left IPL, and decreased DC in the right STG and right MTG was found in the MDD group. With an area under the ROC (AUC) of 0.779, the right STG could differentiate MDD patients from HCs and, with an AUC of 0.704, the right MTG could differentiate MDD patients from SD patients. The three composite indexes had good discriminative ability in each pairwise comparison, with AUCs of 0.803, 0.751, and 0.814 for MDD vs. HC, SD vs. HC, and MDD vs. SD, respectively.ConclusionAltered DC in the STG, MTG, IPL, and MFG were identified in depression groups. The DC values of these altered regions and their combinations presented good discriminative ability between HC, SD, and MDD. These findings could help to find effective biomarkers and reveal the potential mechanisms of depression.

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.

Project description:Major depressive disorder (MDD) is a globally prevalent and highly disabling disease characterized by dysfunction of large-scale brain networks. Previous studies have found that static functional connectivity is not sufficient to reflect the complicated and time-varying properties of the brain. The underlying dynamic interactions between brain functional networks of MDD remain largely unknown, and it is also unclear whether neuroimaging-based dynamic properties are sufficiently robust to discriminate individuals with MDD from healthy controls since the diagnosis of MDD mainly depends on symptom-based criteria evaluated by clinical observation. Resting-state functional magnetic resonance imaging (fMRI) data of 221 MDD patients and 215 healthy controls were shared by REST-meta-MDD consortium. We investigated the spatial-temporal dynamics of MDD using co-activation pattern analysis and made individual diagnoses using support vector machine (SVM). We found that MDD patients exhibited aberrant dynamic properties (such as dwell time, occurrence rate, transition probability, and entropy of Markov trajectories) in some transient networks including subcortical network (SCN), activated default mode network (DMN), de-activated SCN-cerebellum network, a joint network, activated attention network (ATN), and de-activated DMN-ATN, where some dynamic properties were indicative of depressive symptoms. The trajectories of other networks to deactivated DMN-ATN were more accessible in MDD patients. Subgroup analyses also showed subtle dynamic changes in first-episode drug-naïve (FEDN) MDD patients. Finally, SVM achieved preferable accuracies of 84.69%, 76.77%, and 88.10% in discriminating patients with MDD, FEDN MDD, and recurrent MDD from healthy controls with their dynamic metrics. Our findings reveal that MDD is characterized by aberrant dynamic fluctuations of brain network and the feasibility of discriminating MDD patients using dynamic properties, which provide novel insights into the neural mechanism of MDD.

Project description:Thalamocortical circuitry has a substantial impact on emotion and cognition. Previous studies have demonstrated alterations in thalamocortical functional connectivity (FC), characterized by region-dependent hypo- or hyper-connectivity, among individuals with major depressive disorder (MDD). However, the dynamical reconfiguration of the thalamocortical system over time and potential abnormalities in dynamic thalamocortical connectivity associated with MDD remain unclear. Hence, we analyzed dynamic FC (dFC) between ten thalamic subregions and seven cortical subnetworks from resting-state functional magnetic resonance images of 48 patients with MDD and 57 healthy controls (HCs) to investigate time-varying changes in thalamocortical FC in patients with MDD. Moreover, dynamic laterality analysis was conducted to examine the changes in functional lateralization of the thalamocortical system over time. Correlations between the dynamic measures of thalamocortical FC and clinical assessment were also calculated. We identified four dynamic states of thalamocortical circuitry wherein patients with MDD exhibited decreased fractional time and reduced transitions within a negative connectivity state that showed strong correlations with primary cortical networks, compared with the HCs. In addition, MDD patients also exhibited increased fluctuations in functional laterality in the thalamocortical system across the scan duration. The thalamo-subnetwork analysis unveiled abnormal dFC variability involving higher-order cortical networks in the MDD cohort. Significant correlations were found between increased dFC variability with dorsal attention and default mode networks and the severity of symptoms. Our study comprehensively investigated the pattern of alteration of the thalamocortical dFC in MDD patients. The heterogeneous alterations of dFC between the thalamus and both primary and higher-order cortical networks may help characterize the deficits of sensory and cognitive processing in MDD.

Dataset Information

Aberrant degree centrality profiles during rumination in major depressive disorder.

Publications

Aberrant degree centrality profiles during rumination in major depressive disorder.

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