Plasma biomarkers in drug-naïve schizophrenia with severe cognitive impairment via targeted metabolomics

Cognitive impairment is the core symptom of schizophrenia (SZ). Early recognition of cognitive dysfunction is of great significance. Here, we used a metabolome-targeted approach to explore potential biomarkers associated with severe cognitive impairment in drug-naïve SZ patients.

Plasma metabolites from 108 SZ patients and 55 healthy controls (HC) were analyzed using liquid chromatography-mass spectrometry (LC-MS). Participants were split into discovery (n = 88) and validation (n = 75) sets. The cognitive function was assessed using MATRICS Consensus Cognitive Batter (MCCB), with cognitive deficit score ≥ 3 defined as "severe cognitive impairment" (SCI) and others as "non-severe cognitive impairment"(non-SCI).

We found 21 candidate differential metabolites only present in SCI patients, and they were mainly involved in sphingolipid metabolism and glycerophospholipid metabolism. Furthermore, SM C20:2 and PC ae C36:2 were associated with social cognition and neurocognitive subdimensions of MCCB in SCI patients, while no similar results were found in non-SCI patients. The combination of SM C20:2 and PC ae C36:2 could modestly discriminated SCI subjects from non-SCI patients with an area under the curve (AUC) of 0.685 in discovery set and 0.720 in validation set. Moreover, these 2 candidate differential metabolites enabled distinguishing SZ patients from HC with an AUC of 0.717 in discovery set and 0.786 in validation set.

Our study initially identified 21 candidate differential metabolites and 2 potentially important metabolic pathways related to SCI in drug-naïve SZ patients. SM C20:2 and PC ae C36:2 may serve as biomarkers for cognitive severity assessment in SZ patients.