Peripheral blood miR-15b-5p and ABCC6 are candidate biomarkers of early antipsychotic treatment response in first-episode schizophrenia.

Authors

Mengdi Jin, Hongmin Wang, Haixin Li, Shuhua Mao, Mengtong Xie, Yihan Hao, Wenyin Hu, Xiangxiang Zhang, Hongyi Ren, Qiong Yu

Published in

Psychiatry research. Volume 367. Pages 117491. Oct 10, 2026. Epub Oct 10, 2026.

Abstract

Second-generation antipsychotics (SGAs) are the mainstay of schizophrenia treatment, but early response varies markedly across patients. We aimed to identify peripheral miRNA-mRNA signatures associated with subsequent early SGA response and to explore the discriminative and incremental predictive value of selected baseline biomarkers.
First-episode, drug-naïve schizophrenia patients (n = 65) receiving SGA monotherapy were classified as responders or non-responders after 4 weeks using a ≥ 25% reduction in Brief Psychiatric Rating Scale scores. Peripheral blood miRNA and mRNA profiles were analyzed by RNA sequencing in a discovery cohort (n = 15) and validated by qRT-PCR in an independent cohort (n = 50). Exploratory differential-expression and weighted gene co-expression network analyses were used for candidate prioritization in the discovery cohort. Candidate biomarkers were further evaluated by receiver operating characteristic analysis, and dual-luciferase assays.
Exploratory transcriptomic analyses prioritized 45 miRNAs and 190 mRNAs showing differential expression between subsequent responders and non-responders, enriched in transporter activity and neurotrophin signaling pathways. The miR-15b-5p-ABCC6 emerged as the most consistent candidate: miR-15b-5p was upregulated and ABCC6 downregulated in non-responders (both P < 0.001), and luciferase reporter assays supported a sequence-specific interaction between miR-15b-5p and the predicted binding site within the ABCC6 3'-UTR (P < 0.001). In the validation cohort, baseline miR-15b-5p, miR-584-3p, and ABCC6 showed apparent single-marker discrimination between subsequent responders and non-responders, with AUCs of 0.862, 0.935, and 0.856, respectively. The association of miR-15b-5p with treatment response remained significant after adjustment for SGA type.
Baseline peripheral blood miR-15b-5p, miR-584-3p, and ABCC6 were associated with subsequent early antipsychotic response and showed preliminary discriminative value in first-episode schizophrenia. The miR-15b-5p-ABCC6 pair represents a hypothesis-generating candidate interaction supported by sequence-specific reporter evidence and requires further endogenous and mechanistic validation.

PMID:
42874278
Bibliographic data and abstract were imported from PubMed on 15 Oct 2026.

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