FKBP5 and emotional neglect interact to predict individual differences in amygdala reactivity

Authors

  • M. G. White,

    1. Laboratory of NeuroGenetics, Department of Psychology & Neuroscience, Duke University, Durham, NC, USA
    2. Lieber Institute for Brain Development, Baltimore, MD, USA
    Search for more papers by this author
  • R. Bogdan,

    1. Laboratory of NeuroGenetics, Department of Psychology & Neuroscience, Duke University, Durham, NC, USA
    Search for more papers by this author
  • P. M. Fisher,

    1. Center for Integrated Molecular Brain Imaging, Neurobiology Research Unit, Copenhagen, Denmark
    Search for more papers by this author
  • K. E. Muñoz,

    1. Department of Psychology, University of Pittsburgh, Pittsburgh, PA, USA
    Search for more papers by this author
  • D. E. Williamson,

    Corresponding author
    1. Genetic Epidemiology Program, Department of Psychiatry, University of Texas Health Sciences Center at San Antonio, San Antonio, TX, USA
    • Laboratory of NeuroGenetics, Department of Psychology & Neuroscience, Duke University, Durham, NC, USA
    Search for more papers by this author
  • A. R. Hariri

    1. Laboratory of NeuroGenetics, Department of Psychology & Neuroscience, Duke University, Durham, NC, USA
    2. Institute for Genome Sciences & Policy, Duke University, Durham, NC, USA
    Search for more papers by this author

Corresponding author: D. E. Williamson, Genetic Epidemiology Program, Department of Psychiatry, University of Texas Health Sciences Center at San Antonio, 7703 Floyd Curl Drive, Suite 772E, Mail Code 7792, San Antonio, TX 78229–3900, USA. E-mail: williamsonde@uthscsa.edu

Abstract

Individual variation in physiological responsiveness to stress mediates risk for mental illness and is influenced by both experiential and genetic factors. Common polymorphisms in the human gene for FK506 binding protein 5 (FKBP5), which is involved in transcriptional regulation of the hypothalamic–pituitary–adrenal (HPA) axis, have been shown to interact with childhood abuse and trauma to predict stress-related psychopathology. In the current study, we examined if such gene–environment interaction effects may be related to variability in the threat-related reactivity of the amygdala, which plays a critical role in mediating physiological and behavioral adaptations to stress including modulation of the HPA axis. To this end, 139 healthy Caucasian youth completed a blood oxygen level-dependent functional magnetic resonance imaging probe of amygdala reactivity and self-report assessments of emotional neglect (EN) and other forms of maltreatment. These individuals were genotyped for 6 FKBP5 polymorphisms (rs7748266, rs1360780, rs9296158, rs3800373, rs9470080 and rs9394309) previously associated with psychopathology and/or HPA axis function. Interactions between each SNP and EN emerged such that risk alleles predicted relatively increased dorsal amygdala reactivity in the context of higher EN, even after correcting for multiple testing. Two different haplotype analyses confirmed this relationship as haplotypes with risk alleles also exhibited increased amygdala reactivity in the context of higher EN. Our results suggest that increased threat-related amygdala reactivity may represent a mechanism linking psychopathology to interactions between common genetic variants affecting HPA axis function and childhood trauma.

Ancillary