TY - JOUR
T1 - Association of symptom severity and cerebrospinal fluid alterations in recent onset psychosis in schizophrenia-spectrum disorders – An individual patient data meta-analysis
AU - Campana, Mattia
AU - Yakimov, Vladislav
AU - Moussiopoulou, Joanna
AU - Maurus, Isabel
AU - Löhrs, Lisa
AU - Raabe, Florian
AU - Jäger, Iris
AU - Mortazavi, Matin
AU - Benros, Michael E.
AU - Jeppesen, Rose
AU - Meyer zu Hörste, Gerd
AU - Heming, Michael
AU - Giné-Servén, Eloi
AU - Labad, Javier
AU - Boix, Ester
AU - Lennox, Belinda
AU - Yeeles, Ksenija
AU - Steiner, Johann
AU - Meyer-Lotz, Gabriela
AU - Dobrowolny, Henrik
AU - Malchow, Berend
AU - Hansen, Niels
AU - Falkai, Peter
AU - Siafis, Spyridon
AU - Leucht, Stefan
AU - Halstead, Sean
AU - Warren, Nicola
AU - Siskind, Dan
AU - Strube, Wolfgang
AU - Hasan, Alkomiet
AU - Wagner, Elias
N1 - Publisher Copyright:
© 2024 The Authors
PY - 2024/7
Y1 - 2024/7
N2 - Neuroinflammation and blood-cerebrospinal fluid barrier (BCB) disruption could be key elements in schizophrenia-spectrum disorderś(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 Published (6 studies) and unpublished IPD from n = 531 individuals was included in the analyses.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 symptomś 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.
AB - Neuroinflammation and blood-cerebrospinal fluid barrier (BCB) disruption could be key elements in schizophrenia-spectrum disorderś(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 symptomś 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.
KW - Blood–brain barrier
KW - CSF
KW - First episode psychosis
KW - Individual patient data
KW - Meta-analysis
KW - Schizophrenia spectrum disorders
UR - https://www.scopus.com/pages/publications/85190358142
U2 - 10.1016/j.bbi.2024.04.011
DO - 10.1016/j.bbi.2024.04.011
M3 - Article
C2 - 38608742
AN - SCOPUS:85190358142
SN - 0889-1591
VL - 119
SP - 353
EP - 362
JO - Brain, Behavior, and Immunity
JF - Brain, Behavior, and Immunity
ER -