Longitudinal characterization of inflammatory plasma protein signatures in ECT response

Background Electroconvulsive therapy (ECT) is an effective treatment for psychiatric disorders, but its molecular mechanisms are not yet fully elucidated. This study aimed to investigate longitudinal dynamics of inflammatory proteins during ECT and their association with clinical outcomes. Methods Protein expression was measured in 30 patients at multiple time points during the course of ECT using the Olink® inflammation panel. A longitudinal mixed-effects model was used to assess temporal changes in protein levels and their association with symptom severity. Patient-specific correlation analyses examined associations between individual symptom improvement trajectories and protein dynamics. Proteins associated with symptom improvement underwent pathway enrichment analysis to identify underlying signaling mechanisms. A linear model assessed associations between baseline protein expression and treatment response. Results Cystatin D showed significant longitudinal changes during ECT but was not associated with clinical response. Correlation analyses identified 18 immune-related proteins significantly linked to symptom improvement, with 17 showing negative correlations. Notably, IL-4 and IL-20 consistently emerged in both the correlation analysis and linear model, indicating a possible association with ECT-related molecular mechanisms. Pathway enrichment analysis revealed significant involvement of the JAK-STAT signaling pathway, aligning with existing evidence implicating this pathway in the pathophysiology of mood disorders and synaptic plasticity. Conclusion Symptom improvement during ECT is associated with reductions in specific inflammatory and neuroimmune markers, suggesting a potential link to the therapeutic mechanisms. These findings provide preliminary indications of immune involvement in ECT and emphasize the need for larger cohorts to validate results and further investigate immunomodulatory targets in psychiatric treatment.