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Disease severity across psychiatric disorders is linked to pro-inflammatory cytokines

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Title: Disease severity across psychiatric disorders is linked to pro-inflammatory cytokines
Authors: Solomon, Pierre, Budde, Monika, Kohshour, Mojtaba Oraki, Adorjan, Kristina, Heilbronner, Maria, Navarro-Flores, Alba, Papiol, Sergi, Reich-Erkelenz, Daniela, Schulte, Eva, Senner, Fanny, Vogl, Thomas, Kaurani, Lalit, Krüger, Dennis, Sananbenesi, Farahnaz, Pena, Tonatiuh, Burkhardt, Susanne, Schütz, Anna-Lena, Anghelescu, Ion-George, Arolt, Volker, Baune, Bernhardt, Dannlowski, Udo, Dietrich, Detlef, Fallgatter, Andreas, Figge, Christian, Juckel, Georg, Konrad, Carsten, Lang, Fabian, Reimer, Jens, Reininghaus, Eva, Schmauß, Max, Spitzer, Carsten, Wiltfang, Jens, Zimmermann, Jörg, Fischer, André, Falkai, Peter, Schulze, Thomas, Heilbronner, Urs, Poschmann, Jeremie
Contributors: KERANDEL-DION, Céline, Solomon, Pierre, Budde, Monika, Kohshour, Mojtaba Oraki, Adorjan, Kristina, Heilbronner, Maria, Navarro-Flores, Alba, Papiol, Sergi, Reich-Erkelenz, Daniela, Schulte, Eva C., Senner, Fanny, Vogl, Thomas, Kaurani, Lalit, Krüger, Dennis M., Sananbenesi, Farahnaz, Pena, Tonatiuh, Burkhardt, Susanne, Schütz, Anna-Lena, Anghelescu, Ion-George, Arolt, Volker, Baune, Bernhardt T., Poschmann, Jeremie
Source: Brain, behavior and immunity 129, 359-372 (2025). doi:10.1016/j.bbi.2025.06.004
Publisher Information: Elsevier BV, 2025.
Publication Year: 2025
Subject Terms: [SDV] Life Sciences [q-bio], Inflammation, PLAUR, Proteomics, Multi-omics analysis, ddc:150, Cognitive dysfunction, Transdiagnostic clustering, Severe mental disorders, Disease severity
Description: ImportanceNumerous studies indicate that the traditional categorical classification of severe mental disorders (SMD), such as schizophrenia, bipolar disorders, and major depressive disorders, does not align with the underlying biology of those disorders as they frequently overlap in terms of symptoms and risk factors.ObjectiveThis study aimed to identify transdiagnostic patient clusters based on disease severity and explore the underlying biological mechanisms independently of the traditional categorical classification.DesignWe utilized data from 443 participants diagnosed with SMD of the PsyCourse Study, a longitudinal study with deep phenotyping across up to four visits. We performed longitudinal clustering to group patients based on symptom trajectories and cognitive performance. The resulting clusters were compared on cross-sectional variables, including independent measures of severity as well as polygenic risk scores, serum protein quantification, miRNA expression, and DNA methylation.ResultsWe identified two distinct clusters of patients that exhibited marked differences in illness severity but did not differ significantly in age, sex, or diagnostic proportions. We found 19 serum proteins significantly dysregulated between the two clusters. Functional enrichment pointed to a convergence of immune system dysregulation and neurodevelopmental processes.ConclusionThe observed differences in serum protein expression suggest that disease severity is associated with the convergence of immune system dysregulation and neurodevelopmental alterations, particularly involving pathways related to inflammation and brain plasticity. The identification of pro-inflammatory proteins among the differentially expressed markers underscores the potential role of systemic inflammation in the pathophysiology of SMD. These results highlight the importance of considering illness severity as a core dimension in psychiatric research and clinical practice and suggest that targeting immune-related mechanisms may offer promising new therapeutic avenues for patients with SMD.Key pointsQuestionCan analyzing symptom trajectories and cognitive profiles across diagnostic categories reveal clinically relevant subgroups in severe mental disorders?FindingsIn this longitudinal study of 443 individuals with severe mental disorders, two distinct clusters emerged, differing significantly in illness severity, with the more severe group displaying elevated pro-inflammatory serum proteins, suggesting an association between disease severity and inflammation.MeaningThese findings suggest that transdiagnostic clustering clarifies shared mechanisms, underscores the importance of inflammation in severe mental disorders, and highlights a promising avenue for novel therapeutic approaches.
Document Type: Article
Other literature type
File Description: application/pdf
Language: English
ISSN: 0889-1591
DOI: 10.1016/j.bbi.2025.06.004
DOI: 10.1101/2025.03.28.645923
DOI: 10.48620/88794
Access URL: https://inserm.hal.science/inserm-05251637v1
https://inserm.hal.science/inserm-05251637v1/document
https://doi.org/10.1016/j.bbi.2025.06.004
https://resolver.sub.uni-goettingen.de/purl?gro-2/150277
https://resolver.sub.uni-goettingen.de/purl?gro-2/150277
https://resolver.sub.uni-goettingen.de/purl?gro-2/150626
Rights: CC BY
CC BY NC ND
Accession Number: edsair.doi.dedup.....f146b10fdc043aa42583d77a512c2727
Database: OpenAIRE
Description
Abstract:ImportanceNumerous studies indicate that the traditional categorical classification of severe mental disorders (SMD), such as schizophrenia, bipolar disorders, and major depressive disorders, does not align with the underlying biology of those disorders as they frequently overlap in terms of symptoms and risk factors.ObjectiveThis study aimed to identify transdiagnostic patient clusters based on disease severity and explore the underlying biological mechanisms independently of the traditional categorical classification.DesignWe utilized data from 443 participants diagnosed with SMD of the PsyCourse Study, a longitudinal study with deep phenotyping across up to four visits. We performed longitudinal clustering to group patients based on symptom trajectories and cognitive performance. The resulting clusters were compared on cross-sectional variables, including independent measures of severity as well as polygenic risk scores, serum protein quantification, miRNA expression, and DNA methylation.ResultsWe identified two distinct clusters of patients that exhibited marked differences in illness severity but did not differ significantly in age, sex, or diagnostic proportions. We found 19 serum proteins significantly dysregulated between the two clusters. Functional enrichment pointed to a convergence of immune system dysregulation and neurodevelopmental processes.ConclusionThe observed differences in serum protein expression suggest that disease severity is associated with the convergence of immune system dysregulation and neurodevelopmental alterations, particularly involving pathways related to inflammation and brain plasticity. The identification of pro-inflammatory proteins among the differentially expressed markers underscores the potential role of systemic inflammation in the pathophysiology of SMD. These results highlight the importance of considering illness severity as a core dimension in psychiatric research and clinical practice and suggest that targeting immune-related mechanisms may offer promising new therapeutic avenues for patients with SMD.Key pointsQuestionCan analyzing symptom trajectories and cognitive profiles across diagnostic categories reveal clinically relevant subgroups in severe mental disorders?FindingsIn this longitudinal study of 443 individuals with severe mental disorders, two distinct clusters emerged, differing significantly in illness severity, with the more severe group displaying elevated pro-inflammatory serum proteins, suggesting an association between disease severity and inflammation.MeaningThese findings suggest that transdiagnostic clustering clarifies shared mechanisms, underscores the importance of inflammation in severe mental disorders, and highlights a promising avenue for novel therapeutic approaches.
ISSN:08891591
DOI:10.1016/j.bbi.2025.06.004