The Bidirectional Relationship Between Myocardial Infarction and Depression: Risk Factors, Mechanisms, and Interventions

Myocardial infarction (MI) and depression exhibit a bidirectional relationship, in which patients with MI are more susceptible to depression, and individuals with depression face a heightened risk of MI. The two diseases are intricately intertwined via the heart–brain axis. Sex, age, lifestyle, social background, comorbidities, and genetics contribute to and affect the prognosis of this combined condition. Mechanisms involving the autonomic nervous system (ANS), hypothalamic–pituitary–adrenal (HPA) axis, inflammation, thrombosis, tryptophan metabolism, renin–angiotensin–aldosterone system (RAAS), endothelial dysfunction, microRNAs, and gut microbiota, as components of the heart–brain axis, have been implicated in the pathological link between MI and depression. This review outlines the common risk factors and potential mechanisms underlying this bidirectional relationship. It treats the comorbidities of MI and depression as a unified condition, relying on evidence from clinical trials and experimental studies that directly address both diseases together rather than extrapolating from separate studies on MI or depression alone. It also discusses current therapeutic approaches, including non-pharmacological interventions like psychotherapy and exercise, and pharmacological treatments with chemical or natural compounds. Finally, this review identifies significant gaps in the pathophysiology and clinical management of MI with depression, which warrant further investigation.