Journal Article

DZNE-2025-00763

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Disease severity across psychiatric disorders is linked to pro-inflammatory cytokines.

Solomon, P. ; Budde, M. ; Kohshour, M. O. ; Adorjan, K. ; Heilbronner, M. ; Navarro-Flores, A. ; Papiol, S. ; Reich-Erkelenz, D. ; Schulte, E. C. ; Senner, F. ; Vogl, T. ; Kaurani, L.DZNE* ; Krüger, D. M.DZNE* ; Sananbenesi, F.DZNE* ; Pena, T.DZNE* ; Burkhardt, S.DZNE* ; Schütz, A.-L.DZNE* ; Anghelescu, I.-G. ; Arolt, V. ; Baune, B. T. ; Dannlowski, U. ; Dietrich, D. E. ; Fallgatter, A. J.Extern* ; Figge, C. ; Juckel, G. ; Konrad, C. ; Lang, F. U. ; Reimer, J. ; Reininghaus, E. Z. ; Schmauß, M. ; Spitzer, C. ; Wiltfang, J.DZNE* ; Zimmermann, J. ; Fischer, A.DZNE* ; Falkai, P. ; Schulze, T. G. ; Heilbronner, U. ; Poschmann, J.

2025
Elsevier Orlando, Fla. [u.a.]

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Please use a persistent id in citations: doi:10.1016/j.bbi.2025.06.004

Abstract: Numerous 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.This study aimed to identify transdiagnostic patient clusters based on disease severity and explore the underlying biological mechanisms independently of the traditional categorical classification.We 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.We 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.The 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.

Keyword(s): Cognitive dysfunction ; Disease severity ; Inflammation ; Multi-omics analysis ; PLAUR ; Proteomics ; Severe mental disorders ; Transdiagnostic clustering

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Contributing Institute(s):

1. Epigenetics and Systems Medicine in Neurodegenerative Diseases (AG Fischer)
2. Bioinformatics and Genome Dynamics Core (Göttingen) (Bioinformatics Unit (Göttingen))
3. Genome Dynamics in Neurodegenerative Diseases (AG Sananbenesi)
4. Molecular biomarkers for predictive diagnostics of neurodegenerative diseases (AG Wiltfang)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)
2. 899 - ohne Topic (POF4-899) (POF4-899)
3. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2025

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 15 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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