title: The BDNF Val66Met polymorphism modulates the generalization of cued fear responses to a novel context.
abstract: Brain-derived neurotrophic factor (BDNF) has a crucial role in activity-dependent synaptic plasticity and learning and memory. The human functional single-nucleotide BDNF rs6265 (Val66Met) polymorphism has been found to be associated with alteration in neural BDNF release and function correlating with altered emotional behavior. Here, we investigated for the first time the hypothesis that this polymorphism in humans modulates the context dependency of conditioned fear responses. Applying a new paradigm examining generalization of cued fear across contexts, 70 participants stratified for BDNF Val66Met polymorphism were guided through two virtual offices (context) in which briefly illuminated blue and yellow lights served as cues. In the fear context, one light (conditioned stimulus, CS+) but not the other light (CS-) was associated with an electric shock (unconditioned stimulus, US). In the safety context, both lights were presented too, but no US was delivered. During the test phase, lights were presented again both in learning contexts and in a novel generalization context without any US. All participants showed clear fear conditioning to the CS+ in the fear context as indicated by potentiation of startle responses and reports of fear. No fear reactions were found for the CS+ in the safety context. Importantly, generalization of fear responses indicated by the potentiation of startle response to the CS+ compared with the CS- in the novel context was evident only in the Met-carrying group. These are the first results to provide evidence in humans that BDNF modulates the generalization of fear responses. Such context-dependent generalization processes might predispose Met carriers for affective and anxiety disorders.
authors.affiliation: 1] Department of Psychology (Biological Psychology, Clinical Psychology, and Psychotherapy), University of Würzburg, Würzburg, Germany [2] Department of Experimental Psychology (Clinical Psychology and Psychotherapy), University of Regensburg, Regensburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Mühlberger
authors.affiliation: Department of Psychology (Biological Psychology, Clinical Psychology, and Psychotherapy), University of Würzburg, Würzburg, Germany.
authors.forename: Marta
authors.initials: M
authors.lastname: Andreatta
authors.affiliation: Department of Psychology (Biological Psychology, Clinical Psychology, and Psychotherapy), University of Würzburg, Würzburg, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Ewald
authors.affiliation: Department of Psychology (Biological Psychology, Clinical Psychology, and Psychotherapy), University of Würzburg, Würzburg, Germany.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Glotzbach-Schoon
authors.affiliation: Department of Psychology (Biological Psychology, Clinical Psychology, and Psychotherapy), University of Würzburg, Würzburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Tröger
authors.affiliation: 1] Department of Psychology (Biological Psychology, Clinical Psychology, and Psychotherapy), University of Würzburg, Würzburg, Germany [2] Department of Psychiatry, Psychosomatics, and Psychotherapy, University of Würzburg, Würzburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Baumann
authors.affiliation: Department of Psychiatry, Psychosomatics, and Psychotherapy, University of Würzburg, Würzburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Reif
authors.affiliation: Department of Psychiatry, Psychosomatics, and Psychotherapy, University of Würzburg, Würzburg, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Deckert
authors.affiliation: Department of Psychology (Biological Psychology, Clinical Psychology, and Psychotherapy), University of Würzburg, Würzburg, Germany.
authors.forename: Paul
authors.initials: P
authors.lastname: Pauli
mesh_terms: D000328:Adult; D001007:Anxiety / Q000235:genetics; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D003213:Conditioning, Psychological; D003463:Cues; D004192:Discrimination, Psychological; D004311:Double-Blind Method; D004597:Electroshock; D005239:Fear; D005260:Female; D005793:Generalization, Psychological; D005838:Genotype; D006801:Humans; D008297:Male; D010775:Photic Stimulation; D020641:Polymorphism, Single Nucleotide; D013216:Reflex, Startle / Q000235:genetics; D055815:Young Adult
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C579455:BDNF protein, human