title: 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.
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.
  
  
  METHODS
  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.
authors.affiliation: Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Ridder
authors.affiliation: Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Mannheim, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Treutlein
authors.affiliation: Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Nees
authors.affiliation: Institute of Psychology, Department of Clinical Psychology and Psychotherapy, Heidelberg University, Heidelberg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Lang
authors.affiliation: Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Diener
authors.affiliation: Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Wessa
authors.affiliation: Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Kroll
authors.affiliation: Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Pohlack
authors.affiliation: Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Cacciaglia
authors.affiliation: Research Group Behavioral Biology, Central Institute of Mental Health, Mannheim, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Gass
authors.affiliation: Division of Molecular Biology of the Cell I, German Cancer Research Center, Heidelberg, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Schütz
authors.affiliation: Section of Addiction Biology, Division of Psychological Medicine and Psychiatry, Institute of Psychiatry, King's College London, London, UK.
authors.forename: G
authors.initials: G
authors.lastname: Schumann
authors.affiliation: Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Flor
mesh_terms: D000293:Adolescent; D000328:Adult; D000679:Amygdala / Q000502:physiology*; D003214:Conditioning, Classical / Q000502:physiology*; D005108:Extinction, Psychological / Q000502:physiology*; D005239:Fear / Q000502:physiology*; D005260:Female; D059907:Functional Neuroimaging; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008297:Male; D009415:Nerve Net / Q000502:physiology; D010913:Pituitary-Adrenal System / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000502:physiology*; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics*; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D055815:Young Adult; D000099052:CRF Receptor, Type 1
chemical_list: C497713:NR3C1 protein, human; D018019:Receptors, Corticotropin-Releasing Hormone; D011965:Receptors, Glucocorticoid; D000099052:CRF Receptor, Type 1