Association Between Purpureocillium, Amino Acid Metabolism and Cognitive Function in Drug-Naïve, First-Episode Schizophrenia

Cognitive impairments in patients with schizophrenia (SCZ) is associated with poor social functioning and long-term prognosis. Our previous work suggests that some key fungal markers including Purpureocillium, are linked to SCZ. We present a case-control study that includes 136 first-episode, drug-naïve patients with SCZ and 92 healthy controls (HCs). Untargeted liquid chromatography/mass spectrometry (LC/MS) was utilized to measure serum metabolite levels. The abundance of Purpureocillium was assessed using the internal transcribed spacer (ITS) analysis. Cognitive function was measured using the MATRICS Consensus Cognitive Battery. The present study demonstrated significant declines in attention and alertness (AV), speed of processing (SOP) in individuals with SCZ. The abundance of Purpureocillium was found to have a negative correlation with multiple domains of cognitive function. Additionally, SCZ-related metabolic markers 2-Oxoarginine, N-Acetyl-serotonin, Ergothioneine, Isobutyric acid and Biotin were significantly associated with both the abundance of Purpureocillium and cognitive scores (SOP and AV). Mediation analyses revealed that the abundance of Purpureocillium in patients with SCZ had significant direct and indirect effects on SOP and AV) through metabolic markers (2-Oxoarginine, N-Acetyl-serotonin, Ergothioneine). Further, Purpureocillium and the metabolic markers were found to be correlated with inflammation and oxidative stress, both of which have been associated with pathogenesis of SCZ. Our findings suggest that Purpureocillium might be associated with cognitive impairments through its regulation on the metabolism of specific amino acids involved in inflammation and oxidative stress. A better understanding about the fungal-immune-metabolites association may lead to novel treatment approaches to improve cognitive function in patients with SCZ.