The Moderating Role of the FKBP5 Gene Polymorphisms in the Relationship between Attachment Style, Perceived Stress and Psychotic-like Experiences in Non-Clinical Young Adults

Abstract

Numerous studies have reported that stressful life experiences increase the risk of psychosis and psychotic-like experiences (PLEs). Common variations of the FKBP5 gene have been reported to impact the risk of psychosis by moderating the effects of environmental exposures. Moreover, anxious and avoidant attachment styles have been shown to increase both the level of perceived stress and the risk for psychosis development. In the present cross-sectional study, we aimed to investigate whether variants of the FKBP5 gene moderate the effects of attachment styles and the level of perceived stress on the development of PLEs. A total of 535 non-clinical undergraduates were genotyped for six FKBP5 single nucleotide polymorphisms (SNPs) (rs3800373, rs9470080, rs4713902, rs737054, rs1360780 and rs9296158). The Psychosis Attachment Measure (PAM), the Perceived Stress Scale-10 (PSS-10) and the Prodromal Questionnaire 16 (PQ-16) were administered to assess attachment styles, the level of perceived stress and PLEs, respectively. Anxious attachment style, lower levels of perceived self-efficacy and higher levels of perceived helplessness were associated with a significantly higher number of PLEs. The main effects of attachment style on the severity of PLEs were significant in models testing for the associations with perceived self-efficacy and three FKBP5 SNPs (rs1360780, rs9296158 and rs9470080). The main effect of rs38003733 on the number of PLEs was observed, with GG homozygotes reporting a significantly higher number of PLEs in comparison to T allele carriers. In individuals with dominant anxious attachment style, there was a significant effect of the interaction between the FKBP5 rs4713902 SNP and self-efficacy on the severity of PLEs. Among rs4713902 TT homozygotes, a low level of perceived self-efficacy was associated with higher severity of PLEs. In subjects with non-dominant anxious attachment, a low level of perceived self-efficacy was associated with a higher number of PLEs, regardless of the genotype. Our results indicate that the FKBP5 gene might moderate the relationship between attachment, perceived stress and PLEs.

Keywords: FKBP5; HPA-axis; attachment; genetics; psychosis; stress.

Figure 1

Post-hoc comparisons of interactions between FKBP5 rs4713903 polymorphism total PQ-16 score and attachment style. Abbreviations: PSE—perceived self-efficacy, PQ-16—Prodromal Questionnaire 16.