# Alterations in lipid, redox, and energy metabolism in recent onset psychosis: a metabolomics study in non-smoking individuals and matched controls

## TL;DR

A study found that people with recent onset psychosis have distinct metabolic changes in lipids, redox balance, and energy metabolism, unrelated to smoking or medication.

## Contribution

Identified a unique metabolic signature in psychosis, independent of smoking and antipsychotic treatment, using non-smoking participants.

## Key findings

- 28 altered metabolites linked to lipid metabolism, redox imbalances, and energy metabolism in psychosis patients.
- Reduced antioxidant metabolites like cysteine and taurine were consistently observed in psychosis.
- Patients with schizophrenia spectrum disorder showed more severe metabolic disturbances.

## Abstract

Psychotic disorders are associated with systemic metabolic alterations, but these associations may be confounded by smoking. We investigated plasma metabolites in 47 non-smoking recent onset psychosis patients and 36 matched (on age, sex and ethnicity) healthy controls using untargeted LC MS metabolomics. We applied univariate, multivariate and pathway analyses, with subgroup exploration in patients that were diagnosed with schizophrenia spectrum disorder (SSD) specifically. We identified 28 significantly altered metabolites predominantly reflecting lipid metabolism (elevated saturated free fatty acids, glycerol 3 phosphate, conjugated bile acid), redox imbalances (decreased L cysteine, L cystine and taurine) and energy metabolism (reduced pyruvate). These alterations remained significant after adjusting for sex, antipsychotic treatment and metabolic syndrome parameters. Enrichment analyses highlighted taurine/hypotaurine metabolism, alanine/aspartate/glutamate pathways and fatty acid biosynthesis in psychosis. Within the SSD subgroup (n = 28), metabolic perturbations were more pronounced, showing stronger depletion of reducing equivalents and elevated free fatty acids. These findings indicate a specific systemic metabolic signature in psychosis independent of smoking, sex, antipsychotic medication or metabolic syndrome. The pattern suggests mitochondrial dysfunction and increased oxidative stress, accompanied by compensatory lipid mobilization. These findings identify redox and energy metabolism as promising targets for future pharmacological or metabolic interventions in SSD.

•Distinct plasma metabolomic signature found in psychosis, independent of smoking.•Antioxidant metabolites such as cysteine and taurine were consistently reduced.•Schizophrenia spectrum disorder subgroup showed more pronounced metabolic disturbances.•Findings suggest mitochondrial dysfunction, oxidative stress, and a shift toward lipid mobilization.

Distinct plasma metabolomic signature found in psychosis, independent of smoking.

Antioxidant metabolites such as cysteine and taurine were consistently reduced.

Schizophrenia spectrum disorder subgroup showed more pronounced metabolic disturbances.

Findings suggest mitochondrial dysfunction, oxidative stress, and a shift toward lipid mobilization.