Heart rate variability: Evaluating a potential biomarker of anxiety disorders

Establishing quantifiable biological markers associated with anxiety will increase the objectivity of phenotyping and enhance genetic research of anxiety disorders. Heart rate variability (HRV) is a physiological measure reflecting the dynamic relationship between the sympathetic and parasympathetic nervous systems, and is a promising target for further investigation. This review summarizes evidence evaluating HRV as a potential physiological biomarker of anxiety disorders by highlighting literature related to anxiety and HRV combined with investigations of endophenotypes, neuroimaging, treatment response, and genetics. Deficient HRV shows promise as an endophenotype of pathological anxiety and may serve as a noninvasive index of prefrontal cortical control over the amygdala, and potentially aid with treatment outcome prediction. We propose that the genetics of HRV can be used to enhance the understanding of the genetics of pathological anxiety for etiological investigations and treatment prediction. Given the anxiety-HRV link, strategies are offered to advance genetic analytical approaches, including the use of polygenic methods, wearable devices, and pharmacogenetic study designs. Overall, HRV shows promising support as a physiological biomarker of pathological anxiety, potentially in a transdiagnostic manner, with the heart-brain entwinement providing a novel approach to advance anxiety treatment development.