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@ARTICLE{Solomon:279432,
      author       = {Solomon, Pierre and Budde, Monika and Kohshour, Mojtaba
                      Oraki and Adorjan, Kristina and Heilbronner, Maria and
                      Navarro-Flores, Alba and Papiol, Sergi and Reich-Erkelenz,
                      Daniela and Schulte, Eva C and Senner, Fanny and Vogl,
                      Thomas and Kaurani, Lalit and Krüger, Dennis M and
                      Sananbenesi, Farahnaz and Pena, Tonatiuh and Burkhardt,
                      Susanne and Schütz, Anna-Lena and Anghelescu, Ion-George
                      and Arolt, Volker and Baune, Bernhardt T and Dannlowski, Udo
                      and Dietrich, Detlef E and Fallgatter, Andreas J and Figge,
                      Christian and Juckel, Georg and Konrad, Carsten and Lang,
                      Fabian U and Reimer, Jens and Reininghaus, Eva Z and
                      Schmauß, Max and Spitzer, Carsten and Wiltfang, Jens and
                      Zimmermann, Jörg and Fischer, André and Falkai, Peter and
                      Schulze, Thomas G and Heilbronner, Urs and Poschmann,
                      Jeremie},
      title        = {{D}isease severity across psychiatric disorders is linked
                      to pro-inflammatory cytokines.},
      journal      = {Brain, behavior and immunity},
      volume       = {129},
      issn         = {0889-1591},
      address      = {Orlando, Fla. [u.a.]},
      publisher    = {Elsevier},
      reportid     = {DZNE-2025-00763},
      pages        = {359 - 372},
      year         = {2025},
      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.},
      keywords     = {Cognitive dysfunction (Other) / Disease severity (Other) /
                      Inflammation (Other) / Multi-omics analysis (Other) / PLAUR
                      (Other) / Proteomics (Other) / Severe mental disorders
                      (Other) / Transdiagnostic clustering (Other)},
      cin          = {AG Fischer / Bioinformatics Unit (Göttingen) / AG
                      Sananbenesi / AG Wiltfang},
      ddc          = {150},
      cid          = {I:(DE-2719)1410002 / I:(DE-2719)1440016 /
                      I:(DE-2719)1410004 / I:(DE-2719)1410006},
      pnm          = {352 - Disease Mechanisms (POF4-352) / 899 - ohne Topic
                      (POF4-899) / 353 - Clinical and Health Care Research
                      (POF4-353)},
      pid          = {G:(DE-HGF)POF4-352 / G:(DE-HGF)POF4-899 /
                      G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40505822},
      doi          = {10.1016/j.bbi.2025.06.004},
      url          = {https://pub.dzne.de/record/279432},
}