Shared mechanisms of depression and ACS. A shared network of biological and behavioural mechanisms contribute to the reciprocal relationship between ACS and depression. ACS prompts substantial activation of local and systemic inflammation. The unresolved systemic inflammation alters neural functions and activates the HPA axis and sympathetic system via pro-inflammatory mediators. Pro-inflammatory mediators impact CNS signaling to regulate mood and behaviours, resulting in depressive symptoms. Excessive cortisol makes the body vulnerable to acute stress and may amplify the toxic effects of environmental threats. Immune cells in the CNS are also activated and perpetuate the systemic inflammation. Increased catecholamine levels lead to lower HRV and more arrhythmic events. Inflammation also causes platelet and endothelial dysfunction, and impacts plaque formation and stability. Furthermore, depressive symptoms can manifest as excessive intake of food that is high in fat and low in dietary fiber, resulting in gut dysbiosis. This in turn can increase the permeability of the gut barrier and facilitate translocation of the pro-inflammatory factor LPS into the circulation. High energy intake can also cause central obesity and hyperlipidemia. Some harmful metabolites, such as TMAO, can accumulate and directly impact cardiac health. The green arrows in the figure represent the pathophysiological pathways from ACS to depression, while the blue arrows represent the pathways from depression to ACS. Abbreviations: ACS, acute coronary syndrome; ANS, autonomic nervous system; CNS, central nervous system; CRP, C-reactive protein; HPA, hypothalamic-pituitary-adrenal; HRV, heart rate variability; LPS, lipopolysaccharide; LDL, low-density lipoprotein; TMAO, trimethylamine N-oxide; TNF-\alpha, tumor necrosis factor-\alpha.