Depression as a cardiovascular disorder: central-autonomic network, brain-heart axis, and vagal perspectives of low mood

Abstract

If depressive symptoms are not caused by the physiological effects of a substance or other medical or neurological conditions, they are generally classified as mental disorders that target the central nervous system. However, recent evidence suggests that peripheral neural dynamics on cardiovascular control play a causal role in regulating and processing emotions. In this perspective, we explore the dynamics of the Central-Autonomic Network (CAN) and related brain-heart interplay (BHI), highlighting their psychophysiological correlates and clinical symptoms of depression. Thus, we suggest that depression may arise from dysregulated cardiac vagal and sympathovagal dynamics that lead to CAN and BHI dysfunctions. Therefore, treatments for depression should target the nervous system as a whole, with particular emphasis on regulating vagal and BHI dynamics.

Effect of Acute Ketamine Treatment on Sympathetic Regulation Indexed by Electrodermal Activity in Adolescent Major Depression

“…It is believed that this anti-anhedonic effect is due to the downstream regulation of dopaminergic activity via the glutamatergic system [70]. Furthermore, it is well known that depression linked to impaired sympathetic neural regulation represents a risk factor for cardiovascular complications [37,71,72]. Previous studies revealed that ketamine administration is predominantly associated with a sympathomimetic effect on the cardiovascular system, resulting in an increased heart rate or blood pressure [73][74][75][76][77].…”

Association of depression phenotypes and antidepressant treatment with mortality due to cancer and other causes: a community-based cohort study

“…The results of the present study contribute that the C-EDS phenotype increases cancer mortality risk in both men and women, with a higher intensity in the latter. The C-EDS phenotype could be linked to an autonomic dysfunction that has been identified as a potential pathophysiological mechanism of depression (Valenza, 2023 ). In this sense, the heart rate measured in this study, which is regulated by the autonomic nervous system, can be interpreted as an indicator of autonomic dysfunction in men.…”