# Five differentially expressed proteins identified to serve as potential blood biomarkers for schizophrenia screening based on proteomics

**Authors:** Ronghua Li, Xiaoqian Fu, Chuanwei Li, Lian Yuan, Yaozhi Liu, Lin Yang, Xiaojia Fang, Xiaobin Zhang, Guangya Zhang, Xiangdong Du

PMC · DOI: 10.3389/fpsyt.2025.1697383 · Frontiers in Psychiatry · 2026-01-07

## TL;DR

This study identifies five blood proteins that may help detect schizophrenia and suggests possible pathways involved in the disease.

## Contribution

Five differentially expressed proteins are proposed as potential biomarkers for schizophrenia screening.

## Key findings

- Five proteins linked to cytoskeleton, synapse, and immunity were identified as potential biomarkers for schizophrenia.
- Mitogen-activated protein kinase and PI3K-Akt signaling pathways are suggested to be involved in schizophrenia pathology and drug effects.

## Abstract

Schizophrenia is a multifactorial neuropsychiatric disorder characterized by a wide range of debilitating symptoms and relatively poor clinical outcome, bringing a huge burden of disease. However, the underlying pathological mechanism of this disease remains unclear. We aimed to use mass spectrometry to complete proteomics analysis to find biomarkers related to schizophrenia in peripheral blood, which can provide some biomarker for the pathology, diagnosis or treatment of schizophrenia and the focus of future research.

This study was a cross-sectional case-control study involving 46 patients with schizophrenia and 43 healthy controls. All subjects provided early morning fasting cubital venous blood, completed the collection of general demographic data and clinical scale evaluation. At last, the blood samples of all subjects were subjected to mass spectrometry analysis, combined with bioinformatics analysis, to identify and screen differential proteins.

Using nominal P<0.05 (uncorrected) and fold change > 1.5 or < 0.67, 34 proteins were prioritized, among which 22 proteins were up-regulated and 12 were down-regulated; these candidates require false discovery rate controlled verification. Gene ontology over-representation analysis suggested trends in cellular component organization and cell adhesion molecule binding, with no false discovery rate correction. Kyoto encyclopedia of genes and genomes functional enrichment analysis showed that the differential proteins were mainly involved in mitogen-activated protein kinase signaling pathways.

Our research indicates that neural cell adhesion molecule L1, integrin alpha-M, alpha-actinin-1, filamin-A and profilin-1 which are associated with cytoskeleton, synapse and immunity were preliminarily screened as candidate protein markers for schizophrenia. Moreover, mitogen-activated protein kinase signaling pathway may be related to the pathology of schizophrenia, and PI3K-Akt signaling pathway may be related to the efficacy and side effects of antipsychotic drugs.

## Linked entities

- **Proteins:** FLNA (filamin A), pfn1.S (profilin 1 S homeolog)
- **Diseases:** schizophrenia (MONDO:0005090)

## Full-text entities

- **Genes:** PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, ITGAM (integrin subunit alpha M) [NCBI Gene 3684] {aka CD11B, CR3A, HNA-4, MAC-1, MAC1A, MO1A}, ACTN1 (actinin alpha 1) [NCBI Gene 87] {aka BDPLT15}, PFN1 (profilin 1) [NCBI Gene 5216] {aka ALS18, PDB7}, FLNA (filamin A) [NCBI Gene 2316] {aka ABP-280, ABPX, CSBS, CVD1, FGS2, FLN}
- **Diseases:** Schizophrenia (MESH:D012559), neuropsychiatric disorder (MESH:D001523)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12819645/full.md

## References

71 references — full list in the complete paper: https://tomesphere.com/paper/PMC12819645/full.md

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Source: https://tomesphere.com/paper/PMC12819645