Metabolomic biomarkers of psychotic conversion in ultra-high-risk subjects: a pilot study

Psychosis is a psychiatric condition that can become a chronic and severe psychiatric disorder affecting more than 1% of the population. The ultra-high risk (UHR) patients have a transition rate to psychosis of 25% after three years. We aimed to identify circulating metabolomic biomarkers for psychotic conversion in UHR patients using nuclear magnetic resonance (NMR) spectroscopy. We used samples from 35 UHR patients: 14 converters (UHR-C) and 21 non-converters (UHR-NC) at inclusion from the ICAAR cohort. Serum samples were analysed using the high-throughput screening IVDr NMR method. R and SIMCA were used for statistical analysis. Several lipoprotein parameters related to HDL and LDL metabolism were downregulated in UHR-C compared to UHR-NC at the time of inclusion. The 3 best lipoproteins to predict psychotic conversion at baseline were H4A1, H4FC, and L4FC (Area under the Curve (AUC) values were 0.81, 0.81, and 0.78, respectively). These lipoproteins were also negatively correlated with PANSS scores. Our study is the first to use NMR technology to identify biomarkers to predict the risk of psychotic transition in UHR subjects. This pilot study found lipoprotein parameters related to ApoA-1 and HDL-cholesterol (subclass 4) as potential biomarkers. These results need to be replicated on a larger sample. This study highlights the importance of the detailed analysis of circulant lipoproteins related to the brain using NMR technology in early psychosis to identify biomarkers of psychotic transitions and perhaps to better understand the physiopathology of psychosis.