Spinal interoceptive pathways as therapeutic targets in depression

Interoception is commonly defined as the process by which the nervous system senses, interprets and integrates signals from the body. Converging theoretical frameworks propose that signals about bodily states are conveyed by spinal interoceptive pathways (SIPs) to a distributed interoceptive system in the brain to update and constrain predictive interoceptive models about upcoming bodily states and contribute to emotional experience. These predictions would then be used by the brain to adjust bodily states and maintain homeostasis through descending projections. It has also been proposed that dysregulated SIPs signaling and interoceptive processing may play a role in the depressive syndrome. However, there is a knowledge gap in our understanding about the role of SIPs in major depressive disorder (MDD) and whether their modulation is feasible to study interoceptive processes and develop novel therapeutic interventions for MDD. Here, we review emerging evidence supporting the exploration of SIPs as novel feasible targets to study and develop neuromodulation-based interventions for MDD. Along this path, the next critical steps and candidate experimental models to identify SIPs target engagement markers are discussed.