Depression and cardiovascular autonomic control: a matter of vagus and sexparadox

Depression is a well-established stress-related risk factor for several diseases, mainly for those with cardiovas-cular outcomes. The mechanisms that link depression disorders with cardiovascular diseases (CVD) includedysfunctions of the autonomic nervous system. Heart rate variability analysis is a widely-used non-invasivemethod that can simultaneously quantify the activity of the two branches of cardiac autonomic neural controland provide insights about their pathophysiological alterations. Recent scientific literature suggests that sexinfluences the relationship between depressive symptoms and cardiac autonomic dysfunction. Moreover, a fewstudies highlight a possible sex paradox: depressed women, despite a greater vagal tone, experience a higher riskof adverse cardiovascular events than depressed men. Although there are striking sex differences in the incidenceof depression, scanty data on this topic are available. Lastly, studies on the heart-brain axis bidirectionality andthe role of sex are fundamental not only to clarify the biological bases of depression-CVD comorbidity, but also todevelop alternative therapies, where vagus nerve appears to be a promising target of non-invasive neuromo-dulation techniques.