Abstract
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.
Highlights
Schizophrenia is a complex mental disorder with multiple risk factors determining its onset, course and psychopathology
More attention has been given to genetic polymorphisms and epigenetic modifications that may contribute to the variability of HPA axis reactivity to stress in hope to find more consistent results linking childhood trauma with the development of psychosis in later life [27]
It has been demonstrated that particular FKBP5 gene polymorphisms have significant influence on the development of psychosis, severity of symptoms and the level of cognitive impairment in patients with schizophrenia [50, 69, 85]
Summary
Schizophrenia is a complex mental disorder with multiple risk factors determining its onset, course and psychopathology. It has been shown that early life traumatic experiences may provoke a cascade of biological effects resulting in dysregulation of the HPA axis [25, 26] and increasing the risk of psychosis In this line of research, stress hormones levels have been investigated as well as their association with schizophrenia symptomatology providing mixed results. More attention has been given to genetic polymorphisms and epigenetic modifications that may contribute to the variability of HPA axis reactivity to stress in hope to find more consistent results linking childhood trauma with the development of psychosis in later life [27] In this narrative review, we concentrate on one of the genes related to the response to stress associated with the HPA axis – the FKBP5 gene. We provide a summary of evidence and directions for future studies
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