Brain injury biomarkers in major and simple neurocognitive psychosis: association with tryptophan catabolites

BackgroundSchizophrenia is categorized into qualitatively distinct classes, i.e. major (MNP) and simple (SNP) neurocognitive psychosis. MNP is accompanied by more severe neurocognitive deficits and symptomatology, activated immune-inflammatory and oxidative stress pathways, and induction of the tryptophan catabolite (TRYCAT) pathway with increased quinolinic acid (QA) and lowered kynurenic acid (KA) levels. AimsTo examine whether MNP and increased QA levels are associated with increased brain injury markers, including S100 calcium-binding protein B (S100B), neuroepithelial stem cell protein (Nestin), neuron-specific enolase (NSE), phosphorylated tau217 (pTau217), and glial fibrillary acidic protein (GFAP). MethodsThis case-control study included 52 MNP subjects, 68 SNP subjects, and 60 healthy controls and assessed the above brain injury biomarkers and TRYCATs. ResultsNSE and GFAP were significantly higher in MNP than in SNP, and in both MNP or SNP than in controls. Serum S100B levels were substantially higher in MNP than in controls and SNP. The results indicate injuries to neurofilaments in MNP and SBP, and that MNP is additionally characterized by damage to cell bodies, axons, glial cell projections, reduced neurogenesis and synaptic plasticity as compared with SNP. Increased QA levels and lowered KA predict increased pTau217, NSE and GFAP. The QA/KA ratio is the best predictor of these three brain injury markers ConclusionsThese findings validate the differentiation between the two distinct subclasses with MNP being characterized by more profound injuries to brain cells and structures as compared with SNP. Increases in peripheral QA levels may contribute to these brain injuries in MNP.