Interaction between FKBP5 and childhood trauma and risk of aggressive behavior

Arch Gen Psychiatry. 2012 Jan;69(1):62-70. doi: 10.1001/archgenpsychiatry.2011.152.


Context: Childhood trauma may predispose individuals to aggressive behavior, and both childhood trauma and aggressive behavior are associated with hypothalamic-pituitary-adrenal axis dysregulation.

Objective: To determine whether there would be an interaction between genetic variation in FKBP5 and childhood trauma in predicting aggressive behavior.

Design: Cross-sectional study. Four FKBP5 single-nucleotide polymorphisms used in previous studies (rs3800373, rs9296158, rs1360780, and rs9470080) were genotyped. Three diplotypes were derived from 2 major putatively functional haplotypes regulating protein expression that were previously associated with glucocorticoid receptor sensitivity.

Setting: Penitentiary District of Abruzzo-Molise in central Italy.

Participants: A population of 583 male Italian prisoners recruited between 2005 and 2008.

Main outcome measures: A comprehensive analysis of aggression and impulsivity was undertaken using the Brown-Goodwin Lifetime History of Aggression (BGHA) questionnaire, the Buss-Durkee Hostility Inventory (BDHI), and the Barratt Impulsiveness Scale (BIS). A history of childhood trauma was investigated with the Childhood Trauma Questionnaire. The interaction between the FKBP5 diplotypes and childhood trauma on measures of aggression was analyzed. Analyses were replicated with a second behavioral measure of aggression: violent behavior in jail. Individual single-nucleotide polymorphism analysis was performed.

Results: Childhood trauma had a significant effect on BGHA and BDHI scores but not on BIS scores. We observed a significant influence of the FKBP5 high-expression diplotype on both a lifetime history of aggressive behavior (BGHA) (P = .012) and violent behavior in jail (P = .025) but only in individuals exposed to childhood trauma, in particular to physical abuse. No main effect of the FKBP5 diplotypes was observed.

Conclusion: These data suggest that childhood trauma and variants in the FKBP5 gene may interact to increase the risk of overt aggressive behavior.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Adult Survivors of Child Abuse / psychology
  • Aged
  • Aged, 80 and over
  • Aggression / physiology*
  • Aggression / psychology
  • Cross-Sectional Studies
  • Genetic Variation
  • Humans
  • Impulsive Behavior / genetics*
  • Interview, Psychological
  • Italy
  • Male
  • Middle Aged
  • Prisoners / psychology
  • Risk Factors
  • Tacrolimus Binding Proteins / genetics*
  • Young Adult


  • Tacrolimus Binding Proteins
  • tacrolimus binding protein 5