Metabolic-inflammation aspects of depression and cardiovascular disease

Abstract

Major depressive disorder (MDD) and cardiovascular disease (CVD) are prevalent and chronic diseases with high rates of morbidity and mortality. A bidirectional interaction appears to exist between MDD and CVD as epidemiological studies have revealed a strong association. Given the poor prognosis of patients with comorbid CVD and MDD, there is great need for an improved understanding of the mechanisms subserving their interaction. The objective of the current chapter is to explore metabolic-inflammatory aspects of the interaction between MDD and CVD. Inflammation and metabolic dysfunction have been proposed as key substrates with converging pathways of pathogenesis subserving the interaction between CVD and MDD. Metabolic dysfunction may induce inflammation through the release of inflammatory cytokines from visceral adipose tissue, producing a chronic, low-grade inflammatory state. Inflammation may also induce metabolic dysfunction through activation of the hypothalamic-pituitary- adrenal (HPA) axis and increasing insulin resistance. Inflammation and metabolic dysfunction independently and synergistically contribute to the etiology and pathophysiology of both CVD and MDD. For CVD, the metabolicinflammatory pathway is a key player in atherosclerotic plaque formation and propagation. For MDD, inflammation and metabolic dysfunction induce monoamine alterations, microglial activation, impaired neuroplasticity, and impaired brain connectivity ultimately leading to mood and cognitive dysfunction. A further understanding of metabolic-inflammatory aspects may therefore lead to improved preventative and therapeutic strategies for comorbid CVD and MDD. Repurposing of anti- inflammatory and antidiabetic agents may be used in the future in the treatment of MDD; however, currently there is insufficient evidence for routine use.