The Impact of the FKBP5 Gene Polymorphisms on the Relationship between Traumatic Life Events and Psychotic-Like Experiences in Non-Clinical Adults

Filip Stramecki,Łukasz Gawęda,Andrzej Cechnicki,Dorota Frydecka,Paweł Skiba,Błażej Misiak,Joanna Kłosowska,Katarzyna Prochwicz,Edyta Pawlak,Krzysztof Szczygieł,Elżbieta Szmida,Jerzy Samochowiec

doi:10.3390/brainsci11050561

Abstract

Common variations of the FKBP5 gene are implicated in psychotic disorders, by modulating the hypothalamic–pituitary–adrenal axis reactivity to stress. It has been demonstrated that some of them might moderate the effects of childhood trauma on psychosis proneness. However, these associations have not been investigated with respect to traumatic life events (TLEs). Therefore, we aimed to explore whether the FKBP5 polymorphisms moderate the effects of TLEs on the level of psychotic-like experiences (PLEs). A total of 535 non-clinical adults were approached for participation, and genotyping of six FKBP5 polymorphisms (rs3800373, rs9470080, rs4713902, rs737054, rs1360780 and rs9296158) was performed. The Prodromal Questionnaire-16 (PQ-16) and the Traumatic Events Checklist (TEC) were administered to assess PLEs and TLEs, respectively. Among the rs1360780 CC homozygotes, a history of physical abuse was associated with significantly higher PQ-16 scores. This difference was not significant in the rs1360780 T allele carriers. Similarly, a history of physical abuse was associated with significantly higher PQ-16 scores in the rs9296158 GG homozygotes but not in the rs9296158 A allele carriers. Finally, emotional neglect was related to significantly higher PQ-16 scores in the rs737054 T allele carriers but not in the rs737054 CC homozygotes. The present study indicates that variation in the FKBP5 gene might moderate the effects of lifetime traumatic events on psychosis proneness.

Highlights

In recent years, a growing body of studies focus on the role of gene–environment interactions in the development of numerous mental disorders, including schizophrenia [1].Traumatic life events (TLEs) have been considered a significant risk factor for the development of psychosis [2] and cognitive impairments in patients with schizophrenia [3], as well as cognitive biases [4] and psychotic-like experiences (PLEs) in non-clinical subjects [5,6].traumatic life events (TLEs) play a pivotal role in the pathophysiology of various mental disorders, including schizophrenia [2,3,7]
Out of 535 individuals approached for participation, 461 individuals provided data on a history of TLEs and the level of Prodromal Questionnaire-16 (PQ-16) (86.2%)
This may be explained by the role of the rs1380780 polymorphism in inducing the FKBP5 gene transcription in response to GR activation [58] followed by stronger cortisol reactivity in response to stress [59] in individuals exposed to trauma carrying the “risk” T allele

Summary

Introduction

A growing body of studies focus on the role of gene–environment interactions in the development of numerous mental disorders, including schizophrenia [1].Traumatic life events (TLEs) have been considered a significant risk factor for the development of psychosis [2] and cognitive impairments in patients with schizophrenia [3], as well as cognitive biases [4] and psychotic-like experiences (PLEs) in non-clinical subjects [5,6].TLEs play a pivotal role in the pathophysiology of various mental disorders, including schizophrenia [2,3,7]. Traumatic life events (TLEs) have been considered a significant risk factor for the development of psychosis [2] and cognitive impairments in patients with schizophrenia [3], as well as cognitive biases [4] and psychotic-like experiences (PLEs) in non-clinical subjects [5,6]. PLEs are considered one of the phenomena that lie on the continuum of psychosis, where non-clinical psychotic symptoms precede the onset of overt psychosis [10] These experiences include bizarre experiences, perceptual abnormalities (e.g., hearing unusual sounds such as clicking, humming or ringing) and delusional-like ideas (e.g., persecutory ideations or magical thinking) that range from perceptual illusions to subclinical attenuated positive symptoms [5]. Early life traumatic experiences increase the prevalence of PLEs in young adults [21], some of whom may even experience frequent hallucinatory and delusional experiences [22]

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