The role of the interaction between the FKBP5 gene and stressful life events in the pathophysiology of schizophrenia: A narrative review

Stressful life events have been associated with increased risk for development of schizophrenia and play a pivotal role in its psychopathology. Genes related to stress response, such as FKBP5 gene associated with hypothalamic–pituitary–adrenal (HPA) axis, modulate brain response to childhood trauma and determine individual susceptibility for development and course of psychosis. It this review we provide an overview of FKBP5 gene role in human neurophysiology, its association with HPA axis and its role in stress response system in animals and humans. Moreover, we took a closer look on the studies showing the interaction between FKBP5 gene and stressful life events in the pathophysiology of schizophrenia. We explain how interactions between trauma and FKBP5 gene polymorphisms contribute to development of the disease, severity of psychotic symptoms and cognitive disturbances. We also discuss epigenetic modifications that may contribute to altered HPA axis reactivity to stress entailing higher risk for development of psychosis. Considering the pivotal role of FKBP5 gene in physiopathology of schizophrenia we discuss a possible use of new therapeutic agents that may influence HPA axis activity related to the FKBP5 protein especially in individuals exposed to early trauma.