Increased Blood-Brain Barrier Permeability of the Thalamus Correlated With Symptom Severity and Brain Volume Alterations in Patients With Schizophrenia

Background: While direct in vivo data from patients is insufficient, cumulative evidence of microvascular dysfunction has shown that the blood-brain barrier (BBB) is disrupted in schizophrenia. In this study, we attempted to test the hypothesis that greater BBB permeability in patients with schizophrenia was associated with clinical characteristics and brain volumetric alterations using dynamic contrast-enhanced magnetic resonance imaging techniques.

Methods: Structural magnetic resonance imaging and dynamic contrast-enhanced magnetic resonance imaging data from 29 patients with schizophrenia and 18 age- and sex-matched control subjects were obtained. We calculated the volume transfer constant (K^trans) value and compared the difference between the 2 groups. The regions with an abnormal K^trans value were extracted as regions of interest (thalamus), and the correlations with clinical characteristics and gray matter volume were analyzed.

Results: The results revealed that K^trans value of the bilateral thalamus was higher in the schizophrenia group as compared to the healthy control group (p < .001). There were significant positive correlations between thalamic mean K^trans value with disease duration (p < .05) and symptom severity (p < .001). Analysis of the thalamic subregions revealed that BBB disruption was significant in the pulvinar, especially the medial pulvinar nucleus and lateral pulvinar nucleus (p < .001). The correlation between the K^trans values and the corresponding volumes was negative for the whole brain, the thalamus, and the thalamic subregions.

Conclusions: These results provide the first in vivo evidence of BBB disruption of thalamus in patients with schizophrenia and suggest that BBB dysfunction might contribute to the pathological brain structural alterations in schizophrenia.