The potential role of ANXA11/ANXA3 protein level ratio in predicting antidepressant treatment outcomes

Eur Arch Psychiatry Clin Neurosci. 2025 Sep 16. doi: 10.1007/s00406-025-02117-6. Online ahead of print.

ABSTRACT

OBJECTIVE: To explore the causal relationship between 2,821 plasma protein level ratios and antidepressant treatment response to uncover the potential molecular mechanisms.

METHODS: We utilized the protein level ratio dataset from the UK Biobank Pharma Proteomics Project (UKB PPP) and the antidepressant treatment dataset from the Psychiatric Genomics Consortium. We employed Mendelian Randomization (MR) analysis to explore the causal relationships between 2,821 protein level ratios and antidepressant treatment. Additionally, we conducted GO/KEGG analysis to uncover associated biological processes, cellular components, molecular functions, and signaling pathways.

RESULTS: We found that the protein level ratio of ANXA11/ANXA3 was significantly positively associated with the positive effects of antidepressant treatment(IVW method(FEM): OR = 1.537, 95%CI = 1.263-1.869, p = 1.730E-05, pFDR = 0.049), suggesting its potential as a biomarker for predicting antidepressant efficacy. Moreover, the GO/KEGG analysis provided new insights into the genetic architecture and molecular mechanisms underlying antidepressant efficacy.

CONCLUSION: Our results highlight the significance of protein level ratios in the pathophysiological processes of depression and offer novel strategies for the development of personalized treatment approaches. Future studies are warranted to further validate these findings and explore their clinical implications.

PMID:40956419 | DOI:10.1007/s00406-025-02117-6