Impaired Functional Brain–Heart Interplay Sustains Depressive Symptomatology

Depressive symptoms are a leading worldwide cause of mental disorders and disability, strongly affecting emotional processing and regulation. Leveraging recent evidence on the cardiogenic generation of emotion, we hypothesize that dysfunctional behavior in depressive symptomatology is sustained by impaired nervous-system-wise dynamics. Accordingly, this study aims to experimentally characterize functional Brain-Heart Interplay (BHI) patterns specific to emotional dysregulation and processing in subjects exhibiting depressive symptoms compared to healthy controls. Functional BHI has been estimated through a synthetic data generation model, separately modeling and quantifying ascending peripheral-to-central, and descending central-to-peripheral interaction in a time-resolved way. Results gathered from a cohort of 72 individuals indicate that depressive symptoms are associated with continuous efferent central-to-peripheral hyperactivity, particularly in neutral and negative valence conditioning, and afferent vagal-to-central hypoactivity. This hypoactivity seems to be specific to negative emotional processing. Moreover, the expected modulation of ascending interplay during emotional elicitation was detected in healthy controls only, whereas a descending central-to-peripheral modulation in response to emotional conditioning has been found associated to depressive symptomatology, for the first time. This study offers novel insights into the systemic investigation of the neurophysiological bases of depression, serving as an exemplary pathological manifestation of the dysfunctional brain-heart axis.