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000279432 037__ $$aDZNE-2025-00763
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000279432 1001_ $$aSolomon, Pierre$$b0
000279432 245__ $$aDisease severity across psychiatric disorders is linked to pro-inflammatory cytokines.
000279432 260__ $$aOrlando, Fla. [u.a.]$$bElsevier$$c2025
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000279432 520__ $$aNumerous 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.
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000279432 650_7 $$2Other$$aCognitive dysfunction
000279432 650_7 $$2Other$$aDisease severity
000279432 650_7 $$2Other$$aInflammation
000279432 650_7 $$2Other$$aMulti-omics analysis
000279432 650_7 $$2Other$$aPLAUR
000279432 650_7 $$2Other$$aProteomics
000279432 650_7 $$2Other$$aSevere mental disorders
000279432 650_7 $$2Other$$aTransdiagnostic clustering
000279432 7001_ $$aBudde, Monika$$b1
000279432 7001_ $$aKohshour, Mojtaba Oraki$$b2
000279432 7001_ $$aAdorjan, Kristina$$b3
000279432 7001_ $$aHeilbronner, Maria$$b4
000279432 7001_ $$aNavarro-Flores, Alba$$b5
000279432 7001_ $$aPapiol, Sergi$$b6
000279432 7001_ $$aReich-Erkelenz, Daniela$$b7
000279432 7001_ $$aSchulte, Eva C$$b8
000279432 7001_ $$aSenner, Fanny$$b9
000279432 7001_ $$aVogl, Thomas$$b10
000279432 7001_ $$0P:(DE-2719)2812832$$aKaurani, Lalit$$b11$$udzne
000279432 7001_ $$0P:(DE-2719)2812548$$aKrüger, Dennis M$$b12$$udzne
000279432 7001_ $$0P:(DE-2719)2811099$$aSananbenesi, Farahnaz$$b13$$udzne
000279432 7001_ $$0P:(DE-2719)2811063$$aPena, Tonatiuh$$b14$$udzne
000279432 7001_ $$0P:(DE-2719)2810773$$aBurkhardt, Susanne$$b15$$udzne
000279432 7001_ $$0P:(DE-2719)2810585$$aSchütz, Anna-Lena$$b16$$udzne
000279432 7001_ $$aAnghelescu, Ion-George$$b17
000279432 7001_ $$aArolt, Volker$$b18
000279432 7001_ $$aBaune, Bernhardt T$$b19
000279432 7001_ $$aDannlowski, Udo$$b20
000279432 7001_ $$aDietrich, Detlef E$$b21
000279432 7001_ $$0P:(DE-2719)2811701$$aFallgatter, Andreas J$$b22$$udzne
000279432 7001_ $$aFigge, Christian$$b23
000279432 7001_ $$aJuckel, Georg$$b24
000279432 7001_ $$aKonrad, Carsten$$b25
000279432 7001_ $$aLang, Fabian U$$b26
000279432 7001_ $$aReimer, Jens$$b27
000279432 7001_ $$aReininghaus, Eva Z$$b28
000279432 7001_ $$aSchmauß, Max$$b29
000279432 7001_ $$aSpitzer, Carsten$$b30
000279432 7001_ $$0P:(DE-2719)2811317$$aWiltfang, Jens$$b31$$udzne
000279432 7001_ $$aZimmermann, Jörg$$b32
000279432 7001_ $$0P:(DE-2719)2000047$$aFischer, André$$b33$$udzne
000279432 7001_ $$aFalkai, Peter$$b34
000279432 7001_ $$aSchulze, Thomas G$$b35
000279432 7001_ $$aHeilbronner, Urs$$b36
000279432 7001_ $$aPoschmann, Jeremie$$b37
000279432 773__ $$0PERI:(DE-600)1462491-6$$a10.1016/j.bbi.2025.06.004$$gVol. 129, p. 359 - 372$$p359 - 372$$tBrain, behavior and immunity$$v129$$x0889-1591$$y2025
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