An interoceptive model of energy allostasis linking metabolic and mental health

Mental health conditions like depression are associated with an elevated risk of cardiometabolic disorders, yet the mechanisms underlying this comorbidity remain poorly understood. Is metabolic dysfunction a cause of depression, a downstream consequence, or do both stem from shared underlying processes? We argue that neurocognitive mechanisms, particularly those involved in reward and effort processing, interact with metabolic physiology to shape each of these causal pathways. Metabolic signals do not act on the brain in isolation; they are embedded within a broader interoceptive system through which the brain detects and interprets bodily states. This system supports allostasis, the brain's predictive regulation of internal physiological demands. We propose a framework of interoceptive energy allostasis in which disruptions to these predictive processes contribute to the bidirectional relationship between depression and metabolic dysfunction. By integrating perspectives from metabolic and computational psychiatry, this framework offers a theoretical lens to explain the multidirectional comorbidity between mental and metabolic ill-health.


PMID: 40991698 PMCID: PMC12459430 DOI: 10.1126/sciadv.ady4356