Untargeted plasma metabolomics identifies metabolite signatures associated with suicidality status in chronic schizophrenia.

Authors

Lijun Wang, Chenghao Lu, Xiaochun Sun, Wenjie Sun, Yuxin Han, Ziyu Zhou, Yanzhe Li, Nannan Liu, Xinxu Wang, Shen Li, Jie Li

Published in

European archives of psychiatry and clinical neuroscience. Aug 30, 2026. Epub Aug 30, 2026.

Abstract

Suicide contributes substantially to mortality in schizophrenia, yet metabolic signatures associated with suicidality remain poorly understood. We applied untargeted plasma metabolomics with multivariate modeling to identify plasma metabolic signatures associated with suicidality status and clinical features.
We enrolled 146 frequency-matched psychiatric inpatients with chronic schizophrenia: 73 in the suicide-risk (SR) group, defined by current suicidal ideation or suicidal behavior/attempt history at admission, and 73 in the non-suicide-risk (NSR) group. Plasma samples underwent untargeted metabolomic profiling. Discriminating metabolites were identified using orthogonal partial least squares discriminant analysis (OPLS-DA) and Benjamini-Hochberg-adjusted Mann-Whitney U testing (variable importance in projection [VIP] >1.0 and adjusted p <0.05). Stepwise logistic regression with forced clinical covariates generated an exploratory metabolite-based classification model, and Spearman correlations examined associations with Positive and Negative Syndrome Scale (PANSS) and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) scores.
OPLS-DA identified 70 discriminating metabolites (R²Y = 0.938, Q²Y = 0.650), with nominal enrichment of lysine degradation, glutathione metabolism, phenylalanine/tyrosine/tryptophan biosynthesis, and sphingolipid metabolism. Stepwise regression retained six metabolites associated with SR status (area under the curve [AUC] = 0.774): Sphingosine, 3-OH-TML, Ile-Leu+Leu-Ile, TML, Taurine, and 12-HETE. Gamma-Glu-Thr showed the highest VIP (5.003) and broad clinical correlations.
Plasma metabolic differences involving sphingolipid, lysine/carnitine, neuroinflammatory, amino-acid, and glutathione-related pathways were associated with suicidality status in chronic schizophrenia. These exploratory cross-sectional findings require validation in larger longitudinal cohorts using dedicated suicidality assessments.

PMID:
42669098
Bibliographic data and abstract were imported from PubMed on 31 Aug 2026.

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