Identification of Plasma Inflammatory Markers of Adolescent Depression Using the Olink Proteomics Platform

发布时间：2026-01-19 16:34

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. 2023 Oct 11:16:4489-4501.

doi: 10.2147/JIR.S425780. eCollection 2023.

Maolin Cao 3 , Jing Tian 1 , Peijin Cui 1 , Ling Ai 3 , Xue Li 4 , Hua Li 5 , Menghan Gao 1 , Liang Fang 1 2 6 , Libo Zhao 1 2 , Fang Gong 2 6 , Chanjuan Zhou 1 3 4 6

Affiliations

PMID: 37849645 PMCID: PMC10577244 DOI: 10.2147/JIR.S425780

Identification of Plasma Inflammatory Markers of Adolescent Depression Using the Olink Proteomics Platform

Ling Yang et al. J Inflamm Res. 2023.

Abstract

Purpose: The quality of life of worldwide adolescents has been seriously affected by depression. Notably, the inflammatory response is closely associated with the pathophysiology of depression. The present study applied a novel targeted proteomics technology, Olink proximity extension assay (PEA), to profile circulating immune-related proteins in adolescents with depression.

Methods: In the present study, the expression levels of 92 inflammation-related proteins were compared between adolescents with depression (ADs) (n=15) and healthy controls (HCs) (n=15), using the OLINK PEA inflammation panel. We further validated 5 top proteins that were identified through KEGG and GO analyses between 40 HCs and 50 ADs, including CCL4, CXCL5, CXCL6, CXCL11, and IL-18 using enzyme linked immunosorbent assay (ELISA).

Results: We identified 13 differentially expressed proteins between the two cohorts, including 5 up-regulated and 8 down-regulated proteins. Among them, the TRAIL protein levels were significantly negatively correlated with the HAMA-14 score (r=-0.538, p= 0.038), and the levels of transforming growth factor α (TGF-α) were significantly associated with a change in appetite (r = -0.658, p = 0.008). After validation by ELISA, CCL4, CXCL5, CXCL11, and IL-18 showed significant changes between ADs and HCs (p < 0.05), while CXCL6 showed an up-regulated tendency in ADs (p=0.0673). The pooled diagnostic efficacy (area under the curve [AUC]) of these five inflammation markers in clinical diagnosis for adolescent depression was 0.819 (95% CI: 0.735-0.904).

Conclusion: We report a number of inflammation-related plasma biomarkers, which uncover a potential involvement of chemokines, cytokines, and cytokine receptors in adolescent depression. Their roles in the pathophysiology of depression need to be further elucidated.

Keywords: adolescent depression; biomarkers; inflammation; olink proximity extension assay.

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Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1

Flow-chart of inflammation-related markers identification in adolescents with depression.

Figure 2

Differential expressed protein levels between adolescents with depression (ADs) and healthy controls (HCs). (A) Scatter plot of the 13 differentially expressed proteins. (B) Heatmap of 13 differentially expressed proteins. Significance levels: *P < 0.05, **P < 0.01, ***P < 0.001.

Figure 3

Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the differentially expressed proteins. GO enrichment analysis showed the most relevant (A) biological process, (B) cellular component biological process, and (C) molecular function terms related to the differentially expressed proteins. (D) KEGG enrichment analysis showed the top enriched pathway of the differentially expressed proteins.

Figure 4

Relationship between DEP levels and the depressive symptoms in adolescents with depression.

Figure 5

Elisa validation of plasma CCL4, CXCL5, CXCL6, CXCL11, and IL-18 levels in adolescents with depression (ADs) and healthy controls (HCs).

Figure 6

Receiver operating characteristic (ROC) curve for CCL4, CXCL5, CXCL6, CXCL11, IL-18, and the five-protein combination.

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