ArticleAnnals of general psychiatry2026
Analysis of the correlation between the expression levels of caspase-1/IL-1β in the peripheral blood and clinical efficacy in patients with first-episode MDD.
Article in Annals of general psychiatry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundMajor depressive disorder (MDD) pathogenesis is associated with immune-inflammatory dysregulation. This study investigated the mechanistic role of caspase-1-mediated inflammatory pathways in MDD, exploring their therapeutic targeting potential and clinical predictive utility.
methodsPeripheral blood levels of caspase-1, IL-1β, and IL-10 were assessed in MDD patients, with longitudinal analysis of dynamic changes pre-/ post-antidepressant treatment. The predictive performance of the biomarker was validated using leave-one-out cross-validation (LOOCV) and receiver operating characteristic (ROC) analysis. A chronic unpredictable stress (CUS) rat model was established to evaluate the combined therapeutic effects of caspase-1 inhibitors with fluoxetine.
resultsClinical data revealed that expression levels of caspase-1 and IL-1β exhibited an negative correlation with clinical treatment response in patients with MDD, with varying levels observed among patients with differing depression severity. In contrast, IL-10 expression demonstrated a positive correlation with therapeutic efficacy. Following treatment, significant reductions in caspase-1 and IL-1β levels were observed, concurrent with an elevation in IL-10. Caspase-1 demonstrated superior predictive accuracy for treatment response (0.8529 ± 0.3542), yielding an area under the ROC curve (AUC) of 0.72. In animal models, co-administration of a caspase-1 inhibitor with fluoxetine accelerated the onset of antidepressant effects, while simultaneously reducing peripheral blood caspase-1 and IL-1β levels.
conclusionsThe caspase-1/IL-1β axis contributes to MDD pathogenesis by disrupting the pro-inflammatory/anti-inflammatory balance. Its mediated immune response pattern represents a potential therapeutic target for novel antidepressant development. Combined caspase-1 modeling provides a reliable tool for predicting clinical efficacy in MDD, while caspase-1-targeted intervention strategies may overcome the limitation of slow onset of action associated with conventional therapies.
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