Association of symptom severity and cerebrospinal fluid alterations in recent 
onset psychosis in schizophrenia-spectrum disorders - An individual patient data
 meta-analysis

Campana, Mattia; Yakimov, Vladislav; Moussiopoulou, Joanna; Maurus, Isabel; Loehrs, Lisa; Raabe, Florian; Jaeger, Iris; Mortazavi, Matin; Benros, Michael E.; Jeppesen, Rose; zu Hoerste, Gerd Meyer; Heming, Michael; Gine-Serven, Eloi; Labad, Javier; Boix, Ester; Lennox, Belinda; Yeeles, Ksenija; Steiner, Johann; Meyer-Lotz, Gabriela; Dobrowolny, Henrik; Malchow, Berend; Hansen, Niels; Falkai, Peter; Siafis, Spyridon; Leucht, Stefan; Halstead, Sean; Warren, Nicola; Siskind, Dan; Strube, Wolfgang; Hasan, Alkomiet; Wagner, Elias

doi:10.1016/j.bbi.2024.04.011

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Association of symptom severity and cerebrospinal fluid alterations in recent onset psychosis in schizophrenia-spectrum disorders - An individual patient data<i> meta</i>-analysis

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Raabe, Florian
Max Planck Institute of Psychiatry, Max Planck Society;

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Citation

Campana, M., Yakimov, V., Moussiopoulou, J., Maurus, I., Loehrs, L., Raabe, F., et al. (2024). Association of symptom severity and cerebrospinal fluid alterations in recent onset psychosis in schizophrenia-spectrum disorders - An individual patient data<i> meta</i>-analysis. BRAIN BEHAVIOR AND IMMUNITY, 119, 353-362. doi:10.1016/j.bbi.2024.04.011.

Cite as: https://hdl.handle.net/21.11116/0000-000F-7A14-2

Abstract

Neuroinflammation and blood-cerebrospinal fluid barrier (BCB) disruption could be key elements in schizophrenia-spectrum disorders (SSDs) etiology and symptom modulation. We present the largest two-stage individual patient data (IPD) meta -analysis, investigating the association of BCB disruption and cerebrospinal fluid (CSF) alterations with symptom severity in first-episode psychosis (FEP) and recent onset psychotic disorder (ROP) individuals, with a focus on sex-related differences. Data was collected from PubMed and EMBASE databases. FEP, ROP and high-risk syndromes for psychosis IPD were included if routine basic CSF-diagnostics were reported. Risk of bias of the included studies was evaluated. Random-effects meta -analyses and mixed-effects linear regression models were employed to assess the impact of BCB alterations on symptom severity. Published (6 studies) and unpublished IPD from n = 531 individuals was included in the analyses. CSF was altered in 38.8 % of individuals. No significant differences in symptom severity were found between individuals with and without CSF alterations (SMD = -0.17, 95 %CI - 0.55 -0.22, p = 0.341). However, males with elevated CSF/ serum albumin ratios or any CSF alteration had significantly higher positive symptom scores than those without alterations (SMD = 0.34, 95 %CI 0.05 -0.64, p = 0.037 and SMD = 0.29, 95 %CI 0.17 -0.41p = 0.005, respectively). Mixed-effects and simple regression models showed no association (p > 0.1) between CSF parameters and symptomatic outcomes. No interaction between sex and CSF parameters was found (p > 0.1). BCB disruption appears highly prevalent in early psychosis and could be involved in positive symptoms severity in males, indicating potential difficult-to-treat states. This work highlights the need for considering BCB breakdown and sex-related differences in SSDs clinical trials and treatment strategies.