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Applying a Dynamical Systems Model and Network Theory to Major Depressive Disorder.

ABSTRACT: Mental disorders like major depressive disorder can be modeled as complex dynamical systems. In this study we investigate the dynamic behavior of individuals to see whether or not we can expect a transition to another mood state. We introduce a mean field model to a binomial process, where we reduce a dynamic multidimensional system (stochastic cellular automaton) to a one-dimensional system to analyse the dynamics. Using maximum likelihood estimation, we can estimate the parameter of interest which, in combination with a bifurcation diagram, reflects the expectancy that someone has to transition to another mood state. After numerically illustrating the proposed method with simulated data, we apply this method to two empirical examples, where we show its use in a clinical sample consisting of patients diagnosed with major depressive disorder, and a general population sample. Results showed that the majority of the clinical sample was categorized as having an expectancy for a transition, while the majority of the general population sample did not have this expectancy. We conclude that the mean field model has great potential in assessing the expectancy for a transition between mood states. With some extensions it could, in the future, aid clinical therapists in the treatment of depressed patients.

SUBMITTER: Kossakowski JJ

PROVIDER: S-EPMC6692450 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Applying a Dynamical Systems Model and Network Theory to Major Depressive Disorder.

Kossakowski Jolanda J JJ Gordijn Marijke C M MCM Riese Harriëtte H Waldorp Lourens J LJ

Frontiers in psychology 20190807

Mental disorders like major depressive disorder can be modeled as complex dynamical systems. In this study we investigate the dynamic behavior of individuals to see whether or not we can expect a transition to another mood state. We introduce a mean field model to a binomial process, where we reduce a dynamic multidimensional system (stochastic cellular automaton) to a one-dimensional system to analyse the dynamics. Using maximum likelihood estimation, we can estimate the parameter of interest w ...[more]

PMID: 31447730

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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:Background and Objectives: Depressive symptoms are prominent in both major depressive disorder (MDD) and bipolar disorder (BD). However, comparative research on the network structure of depressive symptoms in these two diagnostic groups has been limited. This study aims to compare the network structure of depressive symptoms in MDD and BD, providing a deeper understanding of the depressive symptomatology of each disorder. Materials and Methods: The Zung Self-Rating Depressive Scale, a 20-item questionnaire, was administered to assess the depressive symptoms in individuals with MDD (n = 322) and BD (n = 516). A network analysis was conducted using exploratory graph analysis (EGA), and the network structure was analyzed using regularized partial correlation models. To validate the dimensionality of the Zung SDS, principal component analysis (PCA) was adopted. Centrality measures of the depressive symptoms within each group were assessed, followed by a network comparison test between the two groups. Results: In both diagnostic groups, the network analysis revealed four distinct categories, aligning closely with the PCA results. "Depressed affect" emerged as the most central symptom in both MDD and BD. Furthermore, non-core symptoms, "Personal devaluation" in MDD and "Confusion" in BD, displayed strong centrality. The network comparison test did not reveal significant differences in the network structure between MDD and BD. Conclusions: The absence of significant differences in the network structures between MDD and BD suggests that the underlying mechanisms of depressive symptoms may be similar across these disorders. The identified central symptoms, including "Depressed affect", in both disorders and the distinct non-core symptoms in each highlight the complexity of the depressive symptomatology. Future research should focus on validating these symptoms as therapeutic targets and incorporate various methodologies, including non-metric dimension reduction techniques or canonical analysis.

Dataset Information

Applying a Dynamical Systems Model and Network Theory to Major Depressive Disorder.

Publications

Applying a Dynamical Systems Model and Network Theory to Major Depressive Disorder.

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