• Galin Shir and Keren Hanna.
• Azrieli Faculty of Medicine, Bar Ilan University, Safed, Israel; Gonda Interdisciplinary Brain Research Center, Bar Ilan University, Ramat Gan, Israel.
• Neuroscience. 2024 Mar 20; 546: 8810388-103.

AbstractHeart rate variability (HRV),a measure of the fluctuations in the intervals between consecutive heartbeats, is an indicator of changes in the autonomic nervous system. A chronic reduction in HRV has been repeatedly linked to clinical depression. However, the chronological and mechanistic aspects of this relationship, between the neural, physiological, and psychopathological levels, remain unclear. In this review we present evidence by which changes in HRV might precede the onset of depression. We describe several pathways that can facilitate this relationship. First, we examine a theoretical model of the impact of autonomic imbalance on HRV and its role in contributing to mood dysregulation and depression. We then highlight brain regions that are regulating both HRV and emotion, suggesting these neural regions, and the Insula in particular, as potential mediators of this relationship. We also present additional possible mediating mechanisms involving the immune system and inflammation processes. Lastly, we support this model by showing evidence that modification of HRV with biofeedback leads to an improvement in some symptoms of depression. The possibility that changes in HRV precede the onset of depression is critical to put to the test, not only because it could provide insights into the mechanisms of the illness but also because it may offer a predictive anddiagnosticphysiological marker for depression. Importantly, it could also help to develop new effective clinical interventions for treating depression.Copyright © 2024. Published by Elsevier Inc.

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