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. 2025 Aug 3;15(1):28319.
doi: 10.1038/s41598-025-13367-8.

Pilot study of cerebrospinal fluid biomarkers reveals inflammatory changes in patients with paranoid schizophrenia

Franz Felix Konen #  1   2 , Philipp Sebastian Gehring #  1 , Hannah Benedictine Maier  2 , Sebastian Schröder  2 , Seda Nur Türker  2 , Helge Frieling  2   3 , Stefan Bleich  2 , André Huss  4 , Hayrettin Tumani  5 , Daniel Lüdecke  6 , Jürgen Gallinat  6 , Berend Malchow  7 , Niels Hansen  7 , Jens Wiltfang  7   8   9 , Alexandra Neyazi  3   10 , Thomas Skripuletz  11 ; CAP (Cerebrospinal Fluid Analysis in Psychiatry) Consortium
Affiliations

Pilot study of cerebrospinal fluid biomarkers reveals inflammatory changes in patients with paranoid schizophrenia

Franz Felix Konen et al. Sci Rep. .

Abstract

Paranoid schizophrenia is a severe mental illness with both positive and negative symptoms. Currently, the role of peripheral and central inflammation is increasingly suspected as possible factor in the pathogenesis of schizophrenia. This retrospective, monocentric pilot study investigated 35 patients (15/35 female) diagnosed with paranoid schizophrenia after exclusion of possible underlying neuroinflammatory disorders to assess for inflammatory changes of the cerebrospinal fluid (CSF) and associated signs of neurodegeneration. Kappa free light chains (KFLC), a panel of 21 cyto- and chemokines, and neurofilament light chains (NFL) as surrogate parameters for neuro-inflammation and -degeneration were determined in patients with paranoid schizophrenia as well as age- and sex-matched inflammatory (n = 35) and non-inflammatory controls (n = 40). Patients with paranoid schizophrenia exhibited significantly higher intrathecal synthesized fractions of KFLC than non-inflammatory controls. KFLC-positive patients with paranoid schizophrenia had significantly higher NFL concentrations in CSF than KFLC-negative patients according to Reiber´s diagram. NFL concentrations in CSF of patients with paranoid schizophrenia were associated with illness duration, frequency of psychotic episodes, and amount of antipsychotic treatment attempts. This pilot study highlights inflammatory changes in the CSF among a specific subgroup of patients with paranoid schizophrenia, positively correlating with elevated NFL levels in CSF.

Keywords: Cerebrospinal fluid; Chemokines; Cytokines; Kappa free light chains; Neurofilament light chains; Paranoid schizophrenia.

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Conflict of interest statement

Declarations. Competing interests: The authors declare no conflict of interest. PSG, SNT, SS, HF, SB, AH, DL, NH, JW state that there are no conflicts of interest. Outside the submitted work, some authors received honoraria for lectures, travel grants, or research grants. FFK received travel grants from Merck and Novartis. HBM took part in an educational event sponsored by Livanova. HT has participated in meetings sponsored by or received honoraria for acting as an advisor/speaker for Alexion, Bayer, Biogen, Bristol-Myers Squibb, Celgene, Diamed, Fresenius, Fujirebio, GlaxoSmithKline, Horizon, Janssen-Cilag, Merck, Novartis, Roche, Sanofi-Genzyme, Siemens, and Teva. JG has received research funding from the German Federal Ministry of Education and Research, German Science Foundation, and speaker fees from Lundbeck, Janssen-Cilag, Lilly and Boehringer. AN received lecture fees from Novartis and Merck. BM has received speakership fees from Rovi and Recordati. TS reports research support from Alnylam Pharmaceuticals, Bristol-Myers Squibb Foundation for Immuno-Oncology, Claudia von Schilling Foundation, CSL Behring, Else Kröner Fresenius Foundation, Sanofi Genzyme, VHV Stiftung and honoraria for lectures and travel grants from Alexion, Alnylam Pharmaceuticals, Bayer Vital, Biogen, Celgene, Centogene, CSL Behring, Euroimmun, Janssen, Merck Serono, Novartis, Pfizer, Roche, Sanofi, Siemens, Sobi, Teva; all outside the submitted work. All other authors have not received honoraria for lectures, travel grants, or research grants outside the submitted work. Ethics approval and consent to participate: The investigation was approved by the Ethics Committee of MHH (No. 10417_BO_K2022, 08.06.2022; No. 7837_BO_K_2018, 6 April 2018) and followed the rules of the Declaration of Helsinki of 1975 and its revisions. This is a retrospective study and only data were included that were evaluated for patients treatment or diagnostic purposes as part of the clinical routine. Thus, the local Ethics Committee of MHH waived the need for written informed consent from the participants. The data used in this study was anonymized before its use.

Figures

Fig. 1
Fig. 1
Neurofilament light chain (NFL) concentrations in patients with schizophrenia in association with different measures for illness severity. (A) CSF NFL concentrations in patients who experienced three or more psychotic episodes compared to patients in their initial or second episode. (B) Correlation between the number of psychotic episodes and CSF NFL concentrations. (C) CSF NFL concentrations in patients with a history of up to 2 antipsychotic treatment attempts compared to patients with 3 or more distinct antipsychotic treatment attempts. (D) Correlation between the number of months since symptom onset and CSF NFL concentrations. (E) CSF NFL concentrations in patients who exhibited intrathecal KFLC synthesis as indicated by Reiber’s diagram for KFLC compared to KFLC-negative patients. NFL = neurofilament light chain; KFLC = kappa free light chains; KFLC + = intrathecal KFLC synthesis according to Reiber´s diagram for KFLC; KFLC- = no intrathecal KFLC synthesis according to Reiber´s diagram for KFLC; ns = not significant (p-value > 0.05). P-values are indicated above the arrowed line or are given above the graph.
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