Relationship between blood-cerebrospinal fluid barrier integrity, cardiometabolic and inflammatory factors in schizophrenia-spectrum disorders

The blood-cerebrospinal fluid barrier (BCB) builds an integral interface between the central nervous system and the periphery and appears to be impaired in a substantial proportion of individuals with schizophrenia-spectrum disorders (SSD). Even though a disruption of the BCB is associated with higher symptom severity, factors linked to BCB disruption in SSDs have been minimally investigated. To address this gap, 57 inpatients with SSD underwent cerebrospinal fluid (CSF) and blood analyses as well as comprehensive clinical assessments. In a subgroup of 28 participants structural magnetic resonance imaging (MRI) was performed. We developed a BCB dysfunction score, employing principal component analysis of CSF/serum albumin, CSF/serum IgG ratios and total protein levels in CSF, with higher values indicating stronger abnormalities. We calculated multiple regression models to explore the associations between BCB integrity and cardiometabolic, inflammatory, brain morphometric, and clinical measures respectively. BCB dysfunction score was negatively associated with high-density lipoprotein cholesterol and positively associated with total cholesterol, low-density lipoprotein cholesterol, and triglycerides. Furthermore, we observed a trend towards a positive association between BCB dysfunction score and treatment resistance that did not survive multiple testing correction. We did not find significant associations between the BCB composite score and any other assessed cardiometabolic, inflammatory or cerebroventricular measures. These findings suggest that BCB integrity is associated with dyslipidemia in SSD, highlighting the interplay between cardiometabolic risk factors and brain health in SSD. Addressing cardiometabolic health in individuals with SSD might thus have implications beyond physical health, potentially influencing the integrity of the BCB and, consequently, clinical trajectories.