Allostatic load: Implications for the pathophysiology, evolution, and treatment of bipolar disorder

Bipolar disorder is a severe and chronic mental illness that is a leading cause of disability worldwide. It is associated with cognitive impairments and metabolic comorbidities such as obesity, diabetes, and cardiovascular disease. The model of allostasis and allostatic load proposes that internal and environmental stressors solicit adaptive biological system responses driven by mediators such as cytokines, neurotrophins, and glucocorticoids. If chronically activated, these systems become dysregulated and eventually damaging for the brain and body. Bipolar disorder can be conceptualized not only as a disorder born in part from increased allostatic load but also as an allostatic state that leads to heightened allostatic load. In this chapter, we describe many of the alterations seen in the biological mediators involved in the effects of allostasis and allostatic load in bipolar disorder and the opportunities that these represent in the diagnosis, follow-up, and management of patients with this disorder.