Herein we comprehensively review extant studies reporting on stress and bipolar disorder. The overarching aim is to propose a conceptual framework to inform research about the role of stress in the pathophysiology of BD. Computerized databases i.e. PubMed, PsychInfo, Cochrane Library and Scielo were searched using the following terms: ¡°bipolar disorder¡± cross-referenced with ¡°stress¡±, ¡°general reaction to stress¡±, ¡°resilience¡±, ¡°resistance¡±, ¡°recovery¡± ¡°stress-diathesis¡±, ¡°allostasis¡±, and ¡°hormesis¡±.
Data from literature indicate the existence of some theoretical models to understand the influence of stress in the pathophysiology of BD, including classical stress-diathesis model and new models such as allostasis and hormesis. In addition, molecular mechanisms involved in stress adaptation (resistance, resilience and recovery) can also be translated in research strategies to investigate the impact of stress in the pathophysiology of BD.
Most studies are retrospective and/or cross sectional, do not consider the period of development, assess brain function with only one or few methodologies, and use animal models which are not always similar to human phenotypes.
The interaction between stress and brain development is dynamic and complex. In this article we proposed a theoretical model for investigation about the role of stress in the pathophysiology of BD, based on the different kinds of stress adaptation response and their putative neurobiological underpinnings.