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Post-stroke anxiety symptoms moderate the predictive efficacy of MIP1-α on acute ischemic stroke severity

Year: 2026

Type: article

Abstract: Background: Ischemic stroke (IS) elicits a robust neuroinflammatory response in which damage-associated molecular patterns (DAMPs) released from necrotic tissue drive systemic cytokine activation. Although macrophage inflammatory protein-1α (MIP-1α) is a recognized biomarker of stroke severity, its interaction with neuropsychiatric comorbidities, particularly Post-Stroke Anxiety symptoms (PSAS), remains poorly understood. This study examined whether anxiety symptom severity moderates the association between MIP-1α levels and acute stroke severity. Methods: A total of 263 patients with mild-to-moderate ischemic stroke were enrolled. Stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS), and anxiety symptoms were evaluated using the Generalized Anxiety Disorder-7 (GAD-7) scale. To explore potential biomarker-specific pathways, three CC chemokines (MCP-1, MIP-1α, and MIP-1β) were measured. Because primary correlation screens indicated a strong differential profile specifically for MIP-1α across anxiety severity groups, subsequent moderation analyses were focused on MIP-1α as an exploratory, hypothesis-generating objective. Moderation effects were tested using hierarchical linear regression models adjusted for age, sex, and lifestyle factors. Predictive performance was evaluated using receiver operating characteristic (ROC) curve analysis and DeLong's test. Results: Hypothesis-generating analysis revealed a significant interaction between MIP-1α and anxiety symptom severity on NIHSS scores (standardized β = 0.16, p < 0.01). Among patients with lower anxiety (GAD-7 ≤ 4), MIP-1α was inversely associated with stroke severity. In contrast, among patients with higher anxiety (GAD-7 > 4), this association reversed, with higher MIP-1α levels correlating with greater neurological impairment. The integrated model incorporating the MIP-1α × GAD-7 interaction had the highest AUC (0.76) and significantly outperformed Model 1 (AUC = 0.67; p <0.001), but not Model 2 (AUC = 0.74; p = 0.14). Conclusion: Anxiety symptom severity moderates the cross-sectional association between serum MIP-1α levels and acute neurological impairment in ischemic stroke. These findings indicate that the prognostic value of MIP-1α is context-dependent and highlight the importance of joint neuroinflammatory and psychological evaluation during acute stroke care. These findings suggest that anxiety symptom severity moderates the cross-sectional association between MIP-1α and acute neurological impairment. Future prospective studies are needed to clarify these relationships and evaluate whether managing acute anxiety symptoms can influence neuroinflammatory signaling or clinical recovery.

Source: Frontiers in Psychiatry

DOI: 10.3389/fpsyt.2026.1785971