Dataset Information

Trait- and state-like co-activation pattern dynamics in current and remitted major depressive disorder.

ABSTRACT:

Background

Distinguishing between trait- and state-like neural alternations in major depressive disorder (MDD) may advance our understanding of this recurring disorder. We aimed to investigate dynamic functional connectivity alternations in unmedicated individuals with current or past MDD using co-activation pattern analyses.

Methods

Resting-state functional magnetic resonance imaging data were acquired from individuals with first-episode current MDD (cMDD, n = 50), remitted MDD (rMDD, n = 44), and healthy controls (HCs, n = 64). Using a data-driven consensus clustering technique, four whole-brain states of spatial co-activation were identified and associated metrics (dominance, entries, transition frequency) were analyzed with respect to clinical characteristics.

Results

Relative to rMDD and HC, cMDD showed increased dominance and entries of state 1 (primarily involving default mode network (DMN)), and decreased dominance of state 4 (mostly involving frontal-parietal network (FPN)). Among cMDD, state 1 entries correlated positively with trait rumination. Conversely, relative to cMDD and HC, individuals with rMDD were characterized by increased state 4 entries. Relative to HC, both MDD groups showed increased state 4-to-1 (FPN to DMN) transition frequency but reduction in state 3 (spanning visual attention, somatosensory, limbic networks), with the former metric specifically related to trait rumination.

Limitations

Further confirmation with longitudinal studies are required.

Conclusions

Regardless of symptoms, MDD was characterized by increased FPN-to-DMN transitions and reduced dominance of a hybrid network. State-related effect emerged in regions critically implicated in repetitive introspection and cognitive control. Asymptomatic individuals with past MDD were uniquely linked to increased FPN entries. Our findings identify trait-like brain network dynamics that might increase vulnerability to future MDD.

SUBMITTER: Liu C

PROVIDER: S-EPMC10897955 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Publications

Trait- and state-like co-activation pattern dynamics in current and remitted major depressive disorder.

Liu Chengwen C Belleau Emily L EL Dong Daifeng D Sun Xiaoqiang X Xiong Ge G Pizzagalli Diego A DA Auerbach Randy P RP Wang Xiang X Yao Shuqiao S

Journal of affective disorders 20230526

<h4>Background</h4>Distinguishing between trait- and state-like neural alternations in major depressive disorder (MDD) may advance our understanding of this recurring disorder. We aimed to investigate dynamic functional connectivity alternations in unmedicated individuals with current or past MDD using co-activation pattern analyses.<h4>Methods</h4>Resting-state functional magnetic resonance imaging data were acquired from individuals with first-episode current MDD (cMDD, n = 50), remitted MDD ( ...[more]

PMID: 37245549

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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:Temporal neural synchrony disruption can be linked to a variety of symptoms of major depressive disorder (MDD), including mood rigidity and the inability to break the cycle of negative emotion or attention biases. This might imply that altered dynamic neural synchrony may play a role in the persistence and exacerbation of MDD symptoms. Our study aimed to investigate the changes in whole-brain dynamic patterns of the brain functional connectivity and activity related to depression using the hidden Markov model (HMM) on resting-state functional magnetic resonance imaging (rs-fMRI) data. We compared the patterns of brain functional dynamics in a large sample of 314 patients with MDD (65.9% female; age (mean ± standard deviation): 35.9 ± 13.4) and 498 healthy controls (59.4% female; age: 34.0 ± 12.8). The HMM model was used to explain variations in rs-fMRI functional connectivity and averaged functional activity across the whole-brain by using a set of six unique recurring states. This study compared the proportion of time spent in each state and the average duration of visits to each state to assess stability between different groups. Compared to healthy controls, patients with MDD showed significantly higher proportional time spent and temporal stability in a state characterized by weak functional connectivity within and between all brain networks and relatively strong averaged functional activity of regions located in the somatosensory motor (SMN), salience (SN), and dorsal attention (DAN) networks. Both proportional time spent and temporal stability of this brain state was significantly associated with depression severity. Healthy controls, in contrast to the MDD group, showed proportional time spent and temporal stability in a state with relatively strong functional connectivity within and between all brain networks but weak averaged functional activity across the whole brain. These findings suggest that disrupted brain functional synchrony across time is present in MDD and associated with current depression severity.

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

Trait- and state-like co-activation pattern dynamics in current and remitted major depressive disorder.

Background

Methods

Results

Limitations

Conclusions

Publications

Trait- and state-like co-activation pattern dynamics in current and remitted major depressive disorder.

Similar Datasets

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