Interaction between FKBP5 gene and childhood trauma on psychosis, depression and anxiety symptoms in a non-clinical sample

Psychoneuroendocrinology. 2017 Nov:85:200-209. doi: 10.1016/j.psyneuen.2017.08.024. Epub 2017 Aug 26.


Background: Childhood trauma has been associated with a heightened risk for presenting clinical and non-clinical psychopathology in adulthood. Genes related with the stress response, such as the FK506 binding protein 51 (FKBP5), are plausible candidates moderating the effects of childhood trauma on the emergence of such symptoms later on. The present study aimed to explore the moderating role of FKBP5 genetic variability on the association of different types of childhood trauma with subclinical psychosis, depression and anxiety in a non-clinical sample.

Methods: Schizotypy, psychotic-like experiences, depression and anxiety symptoms and childhood trauma were assessed in 808 young adults. Two FKBP5 haplotypic blocks were detected: block 1 (rs3800373 - rs9296158 - rs1360780) and block 2 (rs9470080 - rs4713916). Subjects were classified in two groups according to whether they carried or not the risk haplotype previously described in the literature (block 1: CAT and block 2: TA). Linear regression analyses were used to study (i) the main effects of childhood trauma and FKBP5 haplotype blocks and (ii) their interaction effects on the mentioned forms of psychopathology.

Results: All childhood trauma scales, except sexual abuse, were associated with schizotypy, psychotic-like experiences, depression and anxiety symptoms. None of the analysed symptoms was associated with the main effects of FKBP5 genetic variability. However an interaction effect between block 1 and physical abuse was observed on anxiety, with lower scores in CAT carriers. This effect was driven by SNP 1 and 2. Moreover, an interaction effect between block 2 and physical abuse was identified on the variables tapping depressive and anxiety symptoms. Specifically, non-TA carrier subjects who were exposed to physical abuse were found to be at higher risk for depressive and anxiety symptoms. These effects were driven by SNP 5. No interaction effect was observed for the other variables.

Conclusions: Our data suggest that exposure to childhood physical abuse may increase the risk for sub-clinical depressive and anxiety symptoms depending on FKBP5 genetic variability. Further research is needed to better elucidate the role of FKBP5 on mental health in clinical and non-clinical cohorts.

Keywords: Anxiety; Childhood trauma; Depression; FKBP5 gene; Gene-environment interaction; Psychotic-like experiences; Schizotypy.

MeSH terms

  • Adolescent
  • Adult
  • Adult Survivors of Child Adverse Events*
  • Anxiety* / etiology
  • Anxiety* / genetics
  • Depression* / etiology
  • Depression* / genetics
  • Female
  • Gene-Environment Interaction*
  • Humans
  • Male
  • Middle Aged
  • Psychotic Disorders* / etiology
  • Psychotic Disorders* / genetics
  • Schizotypal Personality Disorder* / etiology
  • Schizotypal Personality Disorder* / genetics
  • Tacrolimus Binding Proteins* / genetics
  • Young Adult


  • Tacrolimus Binding Proteins
  • tacrolimus binding protein 5