Open Access

Joanna Moussiopoulou, Vladislav Yakimov, Lukas Roell, Boris-Stephan Rauchmann, Hannah Toth, Julian Melcher, Iris Jäger, Isabel Lutz, Marcel S. Kallweit, Boris Papazov, Emanuel Boudriot, Klaus Seelos, Amir Dehsarvi, Mattia Campana, Florian Raabe, Isabel Maurus, Lisa Löhrs, Matthias Brendel, Sophia Stöcklein, Peter Falkai, Alkomiet Hasan, Nicolai Franzmeier, Daniel Keeser, Elias Wagner

• Background Blood-brain barrier (BBB) disruptions are presumed to be implicated in schizophrenia-spectrum disorders (SSDs). Previous studies focused on cerebrospinal fluid (CSF) markers, which are imprecise for detecting subtle BBB disruption. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) enables sensitive investigation of subtle BBB leakage in vivo, yet remains unexplored in SSD research. We hypothesized higher leakage in SSDs compared to healthy controls (HCs), indicating a clinical sub-phenotype. Methods Forty-one people with SSDs and forty age- and sex-matched HCs were included in this cross-sectional study employing DCE-MRI, clinical characterization, cognitive assessment, blood and CSF analyses. The volume transfer constant Ktrans, calculated using the Patlak method to estimate the contrast agent transfer between blood and extravascular space, was compared between groups to detect differences in BBB leakage. Results Individuals with SSDs showed higher BBBBackground Blood-brain barrier (BBB) disruptions are presumed to be implicated in schizophrenia-spectrum disorders (SSDs). Previous studies focused on cerebrospinal fluid (CSF) markers, which are imprecise for detecting subtle BBB disruption. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) enables sensitive investigation of subtle BBB leakage in vivo, yet remains unexplored in SSD research. We hypothesized higher leakage in SSDs compared to healthy controls (HCs), indicating a clinical sub-phenotype. Methods Forty-one people with SSDs and forty age- and sex-matched HCs were included in this cross-sectional study employing DCE-MRI, clinical characterization, cognitive assessment, blood and CSF analyses. The volume transfer constant Ktrans, calculated using the Patlak method to estimate the contrast agent transfer between blood and extravascular space, was compared between groups to detect differences in BBB leakage. Results Individuals with SSDs showed higher BBB leakage compared to HCs in a widespread pattern, in brain regions typically affected in SSDs. No significant association was detected between leakage and measures of cognition, symptom severity, peripheral inflammation markers and albumin CSF/serum ratio. Conclusions This is the first study to date reporting BBB leakage in SSDs compared to HCs in multiple brain regions implicated in the disorder. These findings provide insights into disease mechanisms, highlighting the need for further investigation into the role of the BBB in SSDs.…