Dataset Information

Identifying Subgroups of Major Depressive Disorder Using Brain Structural Covariance Networks and Mapping of Associated Clinical and Cognitive Variables.

ABSTRACT:

Background

Identifying data-driven subtypes of major depressive disorder (MDD) holds promise for parsing the heterogeneity of MDD in a neurobiologically informed way. However, limited studies have used brain structural covariance networks (SCNs) for subtyping MDD.

Methods

This study included 145 unmedicated patients with MDD and 206 demographically matched healthy control subjects, who underwent a structural magnetic resonance imaging scan and a comprehensive neurocognitive battery. Patterns of structural covariance were identified using source-based morphometry across both patients with MDD and healthy control subjects. K-means clustering algorithms were applied on dysregulated structural networks in MDD to identify potential MDD subtypes. Finally, clinical and neurocognitive measures were compared between identified subgroups to elucidate the profile of these MDD subtypes.

Results

Source-based morphometry across all individuals identified 28 whole-brain SCNs that encompassed the prefrontal, anterior cingulate, and orbitofrontal cortices; basal ganglia; and cerebellar, visual, and motor regions. Compared with healthy control subjects, individuals with MDD showed lower structural network integrity in three networks including default mode, ventromedial prefrontal cortical, and salience networks. Clustering analysis revealed two MDD subtypes based on the patterns of structural network abnormalities in these three networks. Further profiling revealed that patients in subtype 1 had younger age of onset and more symptom severity as well as greater deficits in cognitive performance than patients in subtype 2.

Conclusions

Overall, we identified two MDD subtypes based on SCNs that differed in their clinical and cognitive profile. Our results represent a proof-of-concept framework for leveraging these large-scale SCNs to parse heterogeneity in MDD.

SUBMITTER: Yang X

PROVIDER: S-EPMC9616319 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Identifying Subgroups of Major Depressive Disorder Using Brain Structural Covariance Networks and Mapping of Associated Clinical and Cognitive Variables.

Yang Xiao X Kumar Poornima P Nickerson Lisa D LD Du Yue Y Wang Min M Chen Yayun Y Li Tao T Pizzagalli Diego A DA Ma Xiaohong X

Biological psychiatry global open science 20210504 2

<h4>Background</h4>Identifying data-driven subtypes of major depressive disorder (MDD) holds promise for parsing the heterogeneity of MDD in a neurobiologically informed way. However, limited studies have used brain structural covariance networks (SCNs) for subtyping MDD.<h4>Methods</h4>This study included 145 unmedicated patients with MDD and 206 demographically matched healthy control subjects, who underwent a structural magnetic resonance imaging scan and a comprehensive neurocognitive batter ...[more]

PMID: 36324992

Similar Datasets

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

Identifying Subgroups of Major Depressive Disorder Using Brain Structural Covariance Networks and Mapping of Associated Clinical and Cognitive Variables.

Background

Methods

Results

Conclusions

Publications

Identifying Subgroups of Major Depressive Disorder Using Brain Structural Covariance Networks and Mapping of Associated Clinical and Cognitive Variables.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets