Display Settings:


Send to:

Choose Destination
See comment in PubMed Commons below
Psychol Med. 2012 Nov;42(11):2325-35. doi: 10.1017/S0033291712000359. Epub 2012 Mar 12.

Brain activation during fear conditioning in humans depends on genetic variations related to functioning of the hypothalamic-pituitary-adrenal axis: first evidence from two independent subsamples.

Author information

  • 1Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • 2Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Mannheim, Germany.
  • 3Institute of Psychology, Department of Clinical Psychology and Psychotherapy, Heidelberg University, Heidelberg, Germany.
  • 4Research Group Behavioral Biology, Central Institute of Mental Health, Mannheim, Germany.
  • 5Division of Molecular Biology of the Cell I, German Cancer Research Center, Heidelberg, Germany.
  • 6Section of Addiction Biology, Division of Psychological Medicine and Psychiatry, Institute of Psychiatry, King's College London, London, UK.



Enhanced acquisition and delayed extinction of fear conditioning are viewed as major determinants of anxiety disorders, which are often characterized by a dysfunctional hypothalamic-pituitary-adrenal (HPA) axis.


In this study we employed cued fear conditioning in two independent samples of healthy subjects (sample 1: n=60, sample 2: n=52). Two graphical shapes served as conditioned stimuli and painful electrical stimulation as the unconditioned stimulus. In addition, guided by findings from published animal studies on HPA axis-related genes in fear conditioning, we examined variants of the glucocorticoid receptor and corticotropin-releasing hormone receptor 1 genes.


Variation in these genes showed enhanced amygdala activation during the acquisition and reduced prefrontal activation during the extinction of fear as well as altered amygdala-prefrontal connectivity.


This is the first demonstration of the involvement of genes related to the HPA axis in human fear conditioning.

[PubMed - in process]
Free PMC Article

Images from this publication.See all images (2)Free text

Fig. 1
Fig. 2
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Cambridge University Press Icon for PubMed Central
    Loading ...
    Write to the Help Desk