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

The blood-cerebrospinal fluid barrier (BCB) is impaired in a substantial proportion of individuals with schizophrenia-spectrum disorders (SSD). Even though 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), blood analyses, and 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. Bayesian linear and logistic regression models were calculated to explore the associations between BCB integrity and cardiometabolic, inflammatory, cerebroventricular, and clinical measures. Our results indicated very strong evidence for a negative association between the BCB dysfunction score and high-density lipoprotein cholesterol, as well as extreme evidence for positive associations between the BCB dysfunction score and total, low-density lipoprotein cholesterol, and triglycerides. Furthermore, there was moderate evidence of a positive association between BCB dysfunction score and treatment resistance. We did not find evidence of 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 and treatment resistance in SSD, highlighting the interplay between cardiometabolic risk factors and brain health in SSD. Addressing cardiometabolic health in individuals with SSD could influence the integrity of the BCB and, consequently, clinical trajectories.