Lithium treatment and stress response in bipolar disorder

Objectives
This article aims to present the mechanisms of stress response in bipolar affective disorder (BPAD), in the context of the efficacy of lithium treatment. The biological concept of stress by Hans Selye is presented, including environmental stressors in the pathogenesis of BPAD. Genetic, epigenetic, and psychological factors are discussed in accordance with the predisposition-stress model. The relationship between the genetic and molecular basis of BPAD and the prophylactic efficacy of lithium are presented, including the negative influence of psychosocial stressors.

Literature review
The literature review was carried out in terms of the genetic basis of bipolar disorder in the context of the stress response, taking into account research on the glucocorticoid receptor (GR) gene and circadian clock genes, as well as on epigenetic mechanisms, i.e. DNA and histone methylation processes. The over 40-year history of research on psychosocial stress in the pathogenesis and the course of BPAD is presented, including a factor of early childhood trauma. The research on the influence of lithium on the biological components of the stress response (i.e. the GSK-3 enzyme, Bcl protein or glutamate concentrations) and the factors of the effectiveness of prophylactic lithium treatment were discussed.

Conclusions
In the pathogenesis of bipolar disorder, genetic and environmental factors interact with each other according to the predisposition-stress model. Psychosocial stress factors, such as early childhood trauma or insufficient social support, significantly reduce the long-term effectiveness of lithium prophylaxis. The most important genetic and molecular components mediating the stress response to lithium prophylactic efficacy concern the polymorphisms of the GR receptor-NR3C1 and the FKBP5 genes.