Symptom networks in major depressive disorder and treatment response: special focus on TRD

Abstract Background Heterogeneous symptoms in major depression contribute to unsuccessful antidepressant treatment, termed treatment-resistant depression (TRD). Psychometric network modeling conceptualizes depression as interplay of symptoms with potential benefits for treatment; however, a knowledg...

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Main Authors: Alexander Kautzky, Lucie Bartova, Markus Dold, Daniel Souery, Stuart Montgomery, Joseph Zohar, Julien Mendlewicz, Chiara Fabbri, Alessandro Serretti, Evgenii Tretiakov, Dan Rujescu, Tibor Harkany, Siegfried Kasper
Format: Article
Language:English
Published: Cambridge University Press 2025-01-01
Series:European Psychiatry
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Online Access:https://www.cambridge.org/core/product/identifier/S092493382502454X/type/journal_article
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Summary:Abstract Background Heterogeneous symptoms in major depression contribute to unsuccessful antidepressant treatment, termed treatment-resistant depression (TRD). Psychometric network modeling conceptualizes depression as interplay of symptoms with potential benefits for treatment; however, a knowledge gap exists regarding networks in TRD. Methods Symptoms from 1,385 depressed patients, assessed by the Montgomery-Åsberg-depression rating scale (MADRS) as part of the “TRD-III” cohort of the multinational research consortium “Group for the Studies of Resistant Depression,” were used for Gaussian graphical network modeling. Networks were estimated for two timepoints, pretreatment and posttreatment, after the establishment of outcomes response, non-response, and TRD. Applying the network-comparison test, edge weights, and symptom centrality was assessed by bootstrapping. Applying the network-comparison test, outcome groups were compared cross-sectionally and longitudinally regarding the networks’ global strength, invariance, and centrality. Results Pretreatment networks did not differ in global strength, but outcome groups showed distinct symptom connections. For both response and TRD, global strength was reduced posttreatment, leading to significant differences between each pair of networks posttreatment. Sadness, lassitude, inability-to-feel, and pessimistic thoughts ranked most centrally in unfavorable outcomes, while reduced-appetite and suicidal thoughts were more densely connected in response. Connections between central symptoms increased in strength following unsuccessful treatment, particularly regarding links involving pessimistic thoughts in TRD. Conclusion Treatment reduced global network strength across outcome groups. However, distinct symptom networks were found in patients showing response to treatment, non-response, and TRD. More easily targetable symptoms such as reduced-appetite were central to networks in patients with response, while pessimistic thoughts may be a key symptom upholding disease burden in TRD.
ISSN:0924-9338
1778-3585