TY  - JOUR
AU  - Solomon, Pierre
AU  - Budde, Monika
AU  - Kohshour, Mojtaba Oraki
AU  - Adorjan, Kristina
AU  - Heilbronner, Maria
AU  - Navarro-Flores, Alba
AU  - Papiol, Sergi
AU  - Reich-Erkelenz, Daniela
AU  - Schulte, Eva C
AU  - Senner, Fanny
AU  - Vogl, Thomas
AU  - Kaurani, Lalit
AU  - Krüger, Dennis M
AU  - Sananbenesi, Farahnaz
AU  - Pena, Tonatiuh
AU  - Burkhardt, Susanne
AU  - Schütz, Anna-Lena
AU  - Anghelescu, Ion-George
AU  - Arolt, Volker
AU  - Baune, Bernhardt T
AU  - Dannlowski, Udo
AU  - Dietrich, Detlef E
AU  - Fallgatter, Andreas J
AU  - Figge, Christian
AU  - Juckel, Georg
AU  - Konrad, Carsten
AU  - Lang, Fabian U
AU  - Reimer, Jens
AU  - Reininghaus, Eva Z
AU  - Schmauß, Max
AU  - Spitzer, Carsten
AU  - Wiltfang, Jens
AU  - Zimmermann, Jörg
AU  - Fischer, André
AU  - Falkai, Peter
AU  - Schulze, Thomas G
AU  - Heilbronner, Urs
AU  - Poschmann, Jeremie
TI  - Disease severity across psychiatric disorders is linked to pro-inflammatory cytokines.
JO  - Brain, behavior and immunity
VL  - 129
SN  - 0889-1591
CY  - Orlando, Fla. [u.a.]
PB  - Elsevier
M1  - DZNE-2025-00763
SP  - 359 - 372
PY  - 2025
AB  - 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.
KW  - Cognitive dysfunction (Other)
KW  - Disease severity (Other)
KW  - Inflammation (Other)
KW  - Multi-omics analysis (Other)
KW  - PLAUR (Other)
KW  - Proteomics (Other)
KW  - Severe mental disorders (Other)
KW  - Transdiagnostic clustering (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:40505822
DO  - DOI:10.1016/j.bbi.2025.06.004
UR  - https://pub.dzne.de/record/279432
ER  -