Refining and integrating schizophrenia pathophysiology - relevance of the allostatic load concept

Abstract

Adaptation to stress leads to the activation of several biological systems that maintain homeostasis and enable effective coping with challenges. These adaptive processes have been designated as 'allostasis'. However, overactivation or aberrant performance of allostatic mechanisms due to chronic stress exposure may exert systemic deleterious effects. This condition has been called 'allostatic load' (AL). The AL concept is a useful framework allowing to understand the mulitisystem physiological dysregulation due to cumulative stressful demands over the lifespan. In the recent years, the AL paradigm has emerged as a novel concept explaining the morbidity and mortality with respect to several mental disorders. In this article, we suggest that AL provides a useful framework to describe schizophrenia - its etiology, course, outcome and comorbidities. Schizophrenia is a severe mental illness that is characterized by multidimensional psychopathology including positive and negative symptoms, affective symptoms and cognitive impairment with several known risk factors and accompanying pathophysiological correlates. However, there is a great need to refine and integrate the plethora of findings reported from various research perspectives. We propose that AL is a meaningful concept integrating findings on pathophysiological underpinnings, factors influencing course of the disorder and the development of co-occurring physical health impairments as well as substance use disorders in schizophrenia. Furthermore, there is an urgent necessity to investigate AL and its correlates in schizophrenia as no studies in this field have been performed so far.

Keywords: Allostatic load; Mediators of allostasis; Pathophysiology; Schizophrenia; Stress.