Review paper
The concept of allostasis and the neurobiology of bipolar affective illness

The concept of allostasis has been applied to psychiatry to explain the underlying mechanisms of psychiatric illnesses, and recently, also those of bipolar disorder (BD). It postulates that stability is achieved through change of specific body systems, called mediators of allostasis. In response to the prolonged action of pathological factors, the accumulation of the effects of allostasis results in multisystemic, adverse changes in the organism, called allostatic load (AL). The mediators of allostasis, including neuroendocrine and immune systems, glucocorticoids and cytokine levels, reflect changed functioning of the body, ultimately affecting the brain, which, through the mechanisms of neuronal plasticity, attempts to adequately manage the allostatic response.

The concept of allostasis applied to BD provides a basis for clarifying the pathogenesis of the disease and refers to other concepts such as “neuroprogression”, “kindling” or “biomarkers”. Episodes of illness are described as periods of allostatic states, which produce additional AL responsible for the progression of illness. The functioning patterns of the hypothalamic-pituitary-adrenal axis (HPA), autonomic nervous system and immune system correspond to physiology of mediators of allostasis, resulting in persistent increase in cortisol levels, proinflammatory cytokines, oxidative stress and the accelerated aging process. Allostatic load affects the brain in reduction of brain-derived neurotrophic factor (BDNF) levels, impaired neurogenesis and synaptic remodelling, ultimately resulting in irreversible cognitive impairment, with permanent disability due to illness. The concept of allostasis also became a theoretical premise for creating the staging model of BD, which evaluates progress of the disease and provides important therapeutic and prognostic implications.