White matter lipidome alterations in the schizophrenia brain

Numerous brain imaging studies have reported white matter alterations in schizophrenia, but the lipidome analysis of the corresponding tissue remains incomplete. In this study, we investigated the lipidome composition of six subcortical white matter regions corresponding to major axonal tracks in both control subjects and schizophrenia patients. All six regions exhibited a consistent pattern of quantitative lipidome alterations in schizophrenia, involving myelin-forming and mitochondria associated lipid classes. While alteration levels of myelin-forming lipids, particularly sphingolipids, aligned with the extent of the myelin changes reported in structural brain imaging studies, a significant decrease of mitochondria in the white matter, indicated by the lipidome alterations, was not previously investigated. To verify this effect, we performed lipidome analysis in a larger set of individuals and in the mitochondria-enriched membrane fraction, as well as directly quantified mitochondrial content. Our results suggest a substantial reduction of the mitochondrial quotient accompanied by the imbalance in myelin lipids in schizophrenia white matter.