Major depressive disorder (MDD) is among the most common mental disorders, with a lifetime prevalence as high as 17% [1]. MDD and heart disease are closely intertwined. Patients with MDD have an ~75% increased risk of cardiovascular disease [2] and 30–74% of patients who have cardiac events will also meet criteria for MDD (Fig. 1a) [3]. Understanding the complex relationship between these two traits is critical to reducing early mortality, as comorbid MDD is associated with a fivefold increased risk of cardiac mortality within 6 months of a myocardial infarction [3]. In addition to the frequently documented, but poorly understood, relationship between MDD and cardiac health, recent evidence also strongly suggests that chronic loneliness—independent from MDD—similarly increases the risk of heart disease and early mortality. Analyses of ~500,000 participants in the UK biobank showed that loneliness increased the risk of cardiovascular disease incidence by 50% [4] and cardiovascular disease death by 30% [5]. This finding among others [6] has prompted public health initiatives to investigate the physical and mental impact of loneliness. Chronic loneliness reflects a discrepancy between a person’s desired and perceived social connectedness, and is experienced by up to 22% of adults [7].
