Post-stroke anxiety symptoms moderate the predictive efficacy of MIP1-α on acute ischemic stroke severity
8 affiliations
- 1School of Mental Health, Wenzhou Medical University
- 2Department of Neurology, Sinopharm North Hospital
- 3College of Public Health, Wenzhou Medical University
- 4Department of Psychiatry, Yale University School of Medicine
- 5The Affiliated Kangning Hospital, Wenzhou Medical University
- 6Wenzhou Key Laboratory of Basic and Translational Research for Mental Disorders, Wenzhou Medical University
- 7Beijing Hui-Long-Guan Hospital, Peking University
- 8Health Development Department, The Third Hospital of Quzhou
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.
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BibTeX
@article{li2026poststroke,
title = {{Post-stroke anxiety symptoms moderate the predictive efficacy of MIP1-α on acute ischemic stroke severity}},
author = {Mingzhe Li and Tengyue Chen and Yan Wang and Minjie Zhou and Xinyi Zhou and Lifei Xing and Hong Huang and Peipei Zhou and Zhonglu Liao and Yanxiang Chang and Xuan Hu and Xingguang Luo and Yu-Hsin Chen and Li Chen and Yanlong Liu and Wei Wang and Fan Wang and Huilan Jiang},
journal = {Frontiers in Psychiatry},
year = {2026},
month = oct,
doi = {10.3389/fpsyt.2026.1785971},
url = {https://www.frontiersin.org/articles/10.3389/fpsyt.2026.1785971/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Post-stroke anxiety symptoms moderate the predictive efficacy of MIP1-α on acute ischemic stroke severity
AU - Mingzhe Li
AU - Tengyue Chen
AU - Yan Wang
AU - Minjie Zhou
AU - Xinyi Zhou
AU - Lifei Xing
AU - Hong Huang
AU - Peipei Zhou
AU - Zhonglu Liao
AU - Yanxiang Chang
AU - Xuan Hu
AU - Xingguang Luo
AU - Yu-Hsin Chen
AU - Li Chen
AU - Yanlong Liu
AU - Wei Wang
AU - Fan Wang
AU - Huilan Jiang
PY - 2026
DA - 2026/10/21
JO - Frontiers in Psychiatry
DO - 10.3389/fpsyt.2026.1785971
UR - https://www.frontiersin.org/articles/10.3389/fpsyt.2026.1785971/full
AB - 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.
SN - 1664-0640
ER -