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Physiol Behav. 2012 Apr 12;106(1):46-50. doi: 10.1016/j.physbeh.2011.10.029. Epub 2011 Nov 3.

Mediators of allostasis and systemic toxicity in bipolar disorder.

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National Institute for Translational Medicine, INCT-TM, Hospital de Clínicas de Porto Alegre, Federal University of Rio Grande do Sul, Rua Ramiro Barcelos, 2350-CEP 90035-903 Porto Alegre, Brazil.


Bipolar disorder is associated with a high rate of medical and psychiatric comorbidities. This burden of illness, along with cognitive impairment, is seen particularly in late cases, after multiple episodes. These changes in clinical presentation that take place over time have been recently conceptualized as "neuroprogression". The concept of allostatic load is instrumental in understanding how the cumulative stress associated with psychiatric disorders translates into bodily wear and tear, thus providing an underlying explanation for illness progression. Allostatic load is engendered by several factors which interact in a nonlinear manner. Glucocorticoids are fundamental mediators; when chronically in excess, glucocorticoids initiate a series of bodily dysfunctions that may include cortisol-related mitochondrial dysfunction, oxidative stress, inflammation and decrease in the expression of neuroprotective factors. In the present review we examine the role of allostatic load in the illness progression that takes place in bipolar disorder.

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