The allostatic triage model of psychopathology (ATP Model): How reallocation of brain energetic resources under stress elicits psychiatric symptoms.

Psychiatric, cardiometabolic, and immune disorders are highly comorbid, and are precipitated by psychological stress. To explain why these conditions co-occur and how stress triggers their pathogenesis, we introduce the Allostatic Triage Model of Psychopathology (ATP Model) that explains psychopathogenesis, and these bidirectional associations through a bioenergetic lens. Stress increases the energy demand on biological systems, which operate on a finite energy budget, increasing the risk of energy scarcity, especially in the brain, which faces high energy needs and limited access to energetic resources. Allostatic processes anticipate stress-induced increases in energy demand and regulate systemic and brain energy allocation from mind-to-mitochondria, a process that we call "allostatic triage". The brain allostatic-interoceptive system generates internal models of systemic and brain metabolism and energy output that are used to produce affective states, which regulate allostasis. In turn, we propose that affect regulates allostatic triage among functional brain networks. Chronic and traumatic stress dysregulates the mitochondrial and brain networks that regulate affect by reducing metabolic efficiency. We propose that stress-induced energy scarcity and affective dysregulation exacerbates allostatic triage to the networks most necessary for short-term survival, at the expense of non-vital processes contributing to long-term optimization and well-being, dysregulating allostasis and driving transdiagnostic disease pathogenesis. Persistent network activation patterns underlying psychiatric symptoms can then become entrenched as psychiatric disorders through activity-dependent neuroplasticity, also known as canalization. Altogether, we propose that stress dysregulates mitochondria, affect, and allostatic triage, impairing allostasis, and driving transdiagnostic pathological states, which are canalized over time into transdiagnostic disease.