Assessment of brain cholesterol metabolism biomarker 24S-hydroxycholesterol in schizophrenia

Plasma 24S-hydroxycholesterol mostly originates in brain tissue and likely reflects the turnover of cholesterol in the central nervous system. As cholesterol is disproportionally enriched in many key brain structures, 24S-hydroxycholesterol is a promising biomarker for psychiatric and neurologic disorders that impact brain structure. We hypothesized that, as schizophrenia patients have widely reported gray and white matter deficits, they would have abnormal levels of plasma 24S-hydroxycholesterol, and that plasma levels of 24S-hydroxycholesterol would be associated with brain structural and functional biomarkers for schizophrenia. Plasma levels of 24S-hydroxycholesterol were measured in 226 individuals with schizophrenia and 204 healthy controls. The results showed that levels of 24S-hydroxycholesterol were not significantly different between patients and controls. Age was significantly and negatively correlated with 24S-hydroxycholesterol in both groups, and in both groups, females had significantly higher levels of 24S-hydroxycholesterol compared to males. Levels of 24S-hydroxycholesterol were not related to average fractional anisotropy of white matter or cortical thickness, or to cognitive deficits in schizophrenia. Based on these results from a large sample and using multiple brain biomarkers, we conclude there is little to no value of plasma 24S-hydroxycholesterol as a brain metabolite biomarker for schizophrenia.