From Physiology to Psychiatry: Key role of vagal interoceptive pathways in emotional control

Biol Psychiatry. 2025 Apr 24:S0006-3223(25)01145-X. doi: 10.1016/j.biopsych.2025.04.012. Online ahead of print.

ABSTRACT

Interoception is the awareness of bodily sensations, conveyed by both hormonal and neural signals. The vagus nerve is the primary neural interoceptive conduit, responsible for transmitting information from peripheral organs to the brain. It is widely accepted that vagal signals are essential for purely physiological functions like blood pressure maintenance, or nutrient intake homeostasis. However, a growing body of evidence, taking advantage of new technological advances, suggests that the vagus nerve also orchestrates or tunes emotions. Disruption of vagal interoceptive feedback prevents normal emotional control in rodents. Importantly, accumulating evidence indicates that pathological disruption of vagal afferent signals also occurs in humans and may constitute an important risk factor for emotional disorders. Hence, alleviating vagal interoceptive deficits may constitute a new therapeutic avenue for neurotic and affective disorders. Considering the technical and safety challenges for direct stimulation of brain regions relevant to emotionality disorders, the vagus nerve offers a safer and more practical route of potentially achieving similar outcomes. Here we will highlight the earliest studies which examined the consequences of manipulations of the vagal afferent neurons on anxiety, fear, and mood, and integrate these older findings with new research investigating the necessity of vagal afferent neurons in mediating the anxiety or mood-altering effects of physiological signals. We will also discuss the evolutionary significance of vagal control over emotional states within the boundaries of “normal” physiology and conclude by discussing the challenges of engaging the vagal interoception as novel therapeutics in mental health disorders.

PMID:40287121 | DOI:10.1016/j.biopsych.2025.04.012