Fig. 1.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-, tumor necrosis factor-.