Multi-omics reveal critical roles of phosphatidylcholine and sphingomyelin in antipsychotic efficacy for schizophrenia.

ABSTRACT: Nearly 30% of patients with schizophrenia respond inadequately to current antipsychotics, with unclear markers and mechanisms of antipsychotic efficacy. A total of 208 patients with schizophrenia treated for 6 weeks with oral paliperidone were analyzed through genotyping, mass spectrometry proteomic, and metabolomic profiling to explore underlying markers and mechanisms of antipsychotic efficacy. Machine learning analysis identified 20 proteins and 20 metabolites at baseline predictive of treatment response. Proteomic and metabolomic models achieved a cross-site mean AUC of 0.923 and 0.816, respectively. A multi-omics ensemble model achieved 0.941. GWAS and differential analyses identified 32 loci (P < 5 × 10^-5), 83 proteins, and 31 metabolites associated with efficacy (P < 0.05

SUBMITTER: Sun J 

PROVIDER: S-EPMC12518867 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature