2026 ECNP Congress

PS01-1152

Higher blood-brain barrier leakage in schizophrenia-spectrum disorders: a replication study using dynamic contrast-enhanced magnetic resonance imaging

Rita Troyas — K. Piasecka, A. Weinhold, V. Yakimov, E. Boudriot, D. Keeser, P. Falkai, A. Schmitt, L. Röell, J. Moussiopoulou · LMU University Hospital, Department of Psychiatry and Psychotherapy, Munich, Germany

2026 ECNP Congress

Introduction

Blood-brain barrier (BBB) leakage has been implicated in the pathophysiology of schizophrenia-spectrum disorders (SSDs) [1]. Previous studies have commonly assessed BBB integrity using the cerebrospinal fluid-to-serum albumin ratio (Qalb) [2]. However, this measure has several limitations, including a lack of specificity [3].

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is an in vivo, minimally invasive technique that enables a direct quantification of BBB permeability [4]. Using this method, our prior work reported a higher BBB leakage in SSDs compared to healthy controls (HCs) across multiple brain regions implicated in the disorder [5]. These findings require replication.

In the present study, we aimed to replicate these findings in an independent cohort and to perform a regional analysis of BBB leakage across the brain.

Methods

A total of eighty-one individuals with SSD (40 newly recruited, 41 from the original cohort) and fifty-two age- and sex- matched HCs (40 from the original cohort) were included in this cross-sectional study. BBB permeability was assessed with DCE-MRI. 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. Group differences in Ktrans were examined withvoxel-wise ANCOVA. To identify brain areas with the highest BBB leakage, the voxel-wise ANCOVA Ktrans map was thresholded at T>3.2 (p<0.001) and masked with Brainnetome and brainstem atlas regions.

Results

Both in the newly recruited SSD and in the entire SSD cohort, this study replicates our previous findings showing higher BBB leakage in individuals with SSDs compared to HCs. Analysis of the entire sample (n = 81 SSD, n = 52 HC) identified 4,412 voxels with significantly increased Ktrans in SSD patients compared to controls. Notably, these group differences were primarily driven by a patient subgroup comprised of seven SSD patients (8.6% of the cohort) who showed markedly elevated BBB leakage. Descriptively, patients within this high-permeability subgroup tended to be older, with longer illness duration and greater cumulative antipsychotic exposure compared with the remainder of the SSD cohort. However, given the small size of this subgroup, formal statistical comparisons are likely to be underpowered and should be interpreted with caution. Furthermore, the regional distribution of increased BBB permeability in the present cohort is consistent with that observed in our previous study, showing an increased BBB permeability predominantly in subcortical structures including the thalamus, hippocampus, amygdala and brainstem nuclei.

Conclusions

In this extended cohort, we replicate previous findings of increased BBB permeability in SSD, supporting its reproducibility as a feature in a subset of patients. The identification of a subgroup of SSD patients with markedly elevated BBB leakage suggest that these patients may represent a biologically defined subgroup.

These findings have important implications for elucidating underlying disease mechanisms in SSDs and highlights the need for future studies focused on defined clinical subgroups to better develop targeted therapeutic strategies.

References

  1. Campana, M., Löhrs, L., Strauß, J., Münz, S., Oviedo-Salcedo, T., Fernando, P., Maurus, I., Raabe, F., Moussiopoulou, J., Eichhorn, P., Falkai, P., Hasan, A., & Wagner, E. (2023). Blood–brain barrier dysfunction and folate and vitamin B12 levels in first-episode schizophrenia-spectrum psychosis: a retrospective chart review. European Archives of Psychiatry and Clinical Neuroscience, 273(8), 1693–1701. https://doi.org/10.1007/s00406-023-01572-3
  2. Pollak, T. A., Drndarski, S., Stone, J. M., David, A. S., McGuire, P., & Abbott, N. J. (2017). The blood–brain barrier in psychosis. The Lancet Psychiatry, 5(1), 79–92. https://doi.org/10.1016/s2215-0366(17)30293-6
  3. Steiner, J., Bogerts, B., Schroeter, M. L., & Bernstein, H. (2011). S100B protein in neurodegenerative disorders. Clinical Chemistry and Laboratory Medicine (CCLM), 49(3), 409–424. https://doi.org/10.1515/cclm.2011.083
  4. Montagne, A., Barnes, S. R., Nation, D. A., Kisler, K., Toga, A. W., & Zlokovic, B. V. (2022). Imaging subtle leaks in the blood–brain barrier in the aging human brain: potential pitfalls, challenges, and possible solutions. GeroScience, 44(3), 1339–1351. https://doi.org/10.1007/s11357-022-00571-x
  5. Moussiopoulou, J., Yakimov, V., Roell, L., Rauchmann, B., Toth, H., Melcher, J., Jäger, I., Lutz, I., Kallweit, M. S., Papazov, B., Boudriot, E., Seelos, K., Dehsarvi, A., Campana, M., Raabe, F., Maurus, I., Löhrs, L., Brendel, M., Stöcklein, S., . . . Wagner, E. (2025). Higher blood–brain barrier leakage in schizophrenia-spectrum disorders: A comparative dynamic contrast-enhanced magnetic resonance imaging study with healthy controls. Brain Behavior and Immunity, 128, 256–265. https://doi.org/10.1016/j.bbi.2025.04.003