Working memory reflects vulnerability to early life adversity as a risk factor for substance use disorder in the FKBP5 cortisol cochaperone polymorphism, rs9296158

PLoS One. 2019 Jun 11;14(6):e0218212. doi: 10.1371/journal.pone.0218212. eCollection 2019.


Early life adversity (ELA) negatively affects health behaviors in adulthood, but pathways from ELA exposure to behavioral outcomes are poorly understood. ELA in childhood and adolescence may translate into adult outcomes by way of modified glucocorticoid signaling. The cortisol cotransporter, FKBP5 has a G-to-A substitution (rs9296158) that hinders cortisol trafficking within target cells, and this impaired glucocorticoid signaling may shape the long-term response to ELA. We used performance on the Stroop test to assess working memory in 546 healthy young adults who had experienced 0, 1, or > 1 forms of ELA in childhood and adolescence and were genotyped for the FKBP5 rs9296158 G-to-A polymorphism. We observed a robust Gene x Environment interaction (F = 9.49, p < .0001) in which increased ELA exposure led to progressively greater Stroop interference in persons carrying AG and AA genotypes of FKBP5 with no such effect in GG carriers. Further work is needed to explore the modification of cognitive function resulting from ELA. Impairments in working memory illustrate how ELA may use glucocorticoid pathways to influence working memory with potential implications for decision-making and risky behavior including substance use disorders.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Female
  • Humans
  • Male
  • Memory, Short-Term*
  • Polymorphism, Genetic*
  • Risk Factors
  • Substance-Related Disorders / genetics*
  • Substance-Related Disorders / physiopathology
  • Tacrolimus Binding Proteins / genetics*


  • Tacrolimus Binding Proteins
  • tacrolimus binding protein 5