{"title":"Antidepressant in treating myocardial infarction complicated with depression via 5-HT/inflammation from heart to brain.","authors":"Lijun Zhang, Meiyan Liu, Haiyang Chen, Yanwei Li, Peijun Rao","doi":"10.1016/j.jad.2025.120048","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>Exploring the potential mechanism by which inflammation and 5-HT linking myocardial infarction (MI) and depression, and to evaluate therapeutic effect of fluoxetine and SN50.</p><p><strong>Methods: </strong>Patients with coronary artery disease (CAD) were recruited; depressive symptoms were evaluated, inflammatory factors were detected, and the effects of selective serotonin reuptake inhibitors (SSRIs) for CAD patients with depression were recorded. Furthermore, fluoxetine and SN50 were administrated separately for treatment in MI mice, SERT knockout mice, and H9C2 cell experiments.</p><p><strong>Results: </strong>CAD patients with depression had higher value of TNF-α, IL-4, IL-17, IFN-α, and IFN-γ (P < 0.05) compared to those without depression. CAD + depression patients were followed up for 2 years, those who received SSRIs treatment experienced lower cardiac events [1 events (3.7 %) vs. 14 events (11.8 %)] than those who did not. The animal experiment showed that MI surgery induced cardiac dysfunction and autonomic nerves injury which were exacerbated by excessive inflammatory response. Moreover, MI mice exhibited depressive behaviors, possibly due to autonomic nerves injury and inflammation in the cortex and hippocampus. Furthermore, fluoxetine and SN50 contributed to improving cardiac function, regulating cardiac vegetative nervous, relieving depressive behaviors, and reducing inflammation via macrophages/TNF-α/TNFR/NF-κB signaling pathway. SERT knockout mice experiment further revealed the association between 5-HT and inflammation. In addition, the H9C2 cell experiment presented demonstrated the anti-inflammatory effect of fluoxetine.</p><p><strong>Conclusion: </strong>This study identified inflammation, autonomic nerves dysfunction/5-HT as critical mechanisms of MI + depression. Antidepressant treatment would benefit both heart and brain. Moreover, anti-inflammation would be a promising approach for treating MI complicated with depression.</p>","PeriodicalId":14963,"journal":{"name":"Journal of affective disorders","volume":" ","pages":"120048"},"PeriodicalIF":4.9000,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of affective disorders","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.jad.2025.120048","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/8/9 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Objective: Exploring the potential mechanism by which inflammation and 5-HT linking myocardial infarction (MI) and depression, and to evaluate therapeutic effect of fluoxetine and SN50.
Methods: Patients with coronary artery disease (CAD) were recruited; depressive symptoms were evaluated, inflammatory factors were detected, and the effects of selective serotonin reuptake inhibitors (SSRIs) for CAD patients with depression were recorded. Furthermore, fluoxetine and SN50 were administrated separately for treatment in MI mice, SERT knockout mice, and H9C2 cell experiments.
Results: CAD patients with depression had higher value of TNF-α, IL-4, IL-17, IFN-α, and IFN-γ (P < 0.05) compared to those without depression. CAD + depression patients were followed up for 2 years, those who received SSRIs treatment experienced lower cardiac events [1 events (3.7 %) vs. 14 events (11.8 %)] than those who did not. The animal experiment showed that MI surgery induced cardiac dysfunction and autonomic nerves injury which were exacerbated by excessive inflammatory response. Moreover, MI mice exhibited depressive behaviors, possibly due to autonomic nerves injury and inflammation in the cortex and hippocampus. Furthermore, fluoxetine and SN50 contributed to improving cardiac function, regulating cardiac vegetative nervous, relieving depressive behaviors, and reducing inflammation via macrophages/TNF-α/TNFR/NF-κB signaling pathway. SERT knockout mice experiment further revealed the association between 5-HT and inflammation. In addition, the H9C2 cell experiment presented demonstrated the anti-inflammatory effect of fluoxetine.
Conclusion: This study identified inflammation, autonomic nerves dysfunction/5-HT as critical mechanisms of MI + depression. Antidepressant treatment would benefit both heart and brain. Moreover, anti-inflammation would be a promising approach for treating MI complicated with depression.
期刊介绍：
The Journal of Affective Disorders publishes papers concerned with affective disorders in the widest sense: depression, mania, mood spectrum, emotions and personality, anxiety and stress. It is interdisciplinary and aims to bring together different approaches for a diverse readership. Top quality papers will be accepted dealing with any aspect of affective disorders, including neuroimaging, cognitive neurosciences, genetics, molecular biology, experimental and clinical neurosciences, pharmacology, neuroimmunoendocrinology, intervention and treatment trials.
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