Antidepressant in treating myocardial infarction complicated with depression via 5-HT/inflammation from heart to brain

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.

5-HT; Anti-inflammation; Antidepressant; Depression; Myocardial infarction; NF-κB.