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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.

Abstract

BACKGROUND:

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.

METHOD:

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.

RESULTS:

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.

CONCLUSIONS:

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

PMID:
22410078
[PubMed - in process]
PMCID:
PMC3466052
Free PMC Article

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