Depression occurs in people of all ages across all world regions; it is the second leading cause of disability and its global burden increased by 37.5% between 1990 and 2010. Autonomic changes are often found in altered mood states and appear to be a central biological substrate linking depression to a number of physical dysfunctions. Alterations of autonomic nervous system functioning that promotes vagal withdrawal are reflected in reductions of heart rate variability (HRV) indexes. Reduced HRV characterizes emotional dysregulation, decreased psychological flexibility and defective social engagement, which in turn are linked to prefrontal cortex hypoactivity. Altogether, these pieces of evidence support the idea that HRV might represent a useful endophenotype for psychological/physical comorbidities, and its routine application should be advised to assess the efficacy of prevention/intervention therapies in a number of psychosomatic and psychiatric dysfunctions. Further research, also making use of appropriate animal models, could provide a significant support to this point of view and possibly help to identify appropriate antidepressant therapies that do not interefere with physical health.

Stressful life events are an important cause of psychopathology. Humans exposed to aversive or stressful experiences show considerable inter-individual heterogeneity in their responses. However, the majority does not develop stress-related psychiatric disorders. The dynamic processes encompassing positive and functional adaptation in the face of significant adversity have been broadly defined as resilience. Traditionally, the assessment of resilience has been confined to self-report measures, both within the general community and putative high-risk populations. Although this approach has value, it is highly susceptible to subjective bias and may not capture the dynamic nature of resilience, as underlying construct. Recognizing the obvious benefits of more objective measures of resilience, research in the field has just started investigating the predictive value of several potential biological markers. This review provides an overview of theoretical views and empirical evidence suggesting that individual differences in heart rate variability (HRV), a surrogate index of resting cardiac vagal outflow, may underlie different levels of resilience toward the development of stress-related psychiatric disorders. Following this line of thought, recent studies describing associations between regional brain morphometric characteristics and resting state vagally-mediated HRV are summarized. Existing studies suggest that the structural morphology of the anterior cingulated cortex (ACC), particularly its cortical thickness, is implicated in the expression of individual differences in HRV. These findings are discussed in light of emerging structural neuroimaging research, linking morphological characteristics of the ACC to psychological traits ascribed to a high-resilient profile and abnormal structural integrity of the ACC to the psychophysiological expression of stress-related mental health consequences. We conclude that a multidisciplinary approach integrating brain structural imaging with HRV monitoring could offer novel perspectives about brain-body pathways in resilience and adaptation to psychological stress.