title: BDNFval66met affects neural activation pattern during fear conditioning and 24 h delayed fear recall.
abstract: Brain-derived neurotrophic factor (BDNF), the most abundant neutrophin in the mammalian central nervous system, is critically involved in synaptic plasticity. In both rodents and humans, BDNF has been implicated in hippocampus- and amygdala-dependent learning and memory and has more recently been linked to fear extinction processes. Fifty-nine healthy participants, genotyped for the functional BDNFval66met polymorphism, underwent a fear conditioning and 24h-delayed extinction protocol while skin conductance and blood oxygenation level dependent (BOLD) responses (functional magnetic resonance imaging) were acquired. We present the first report of neural activation pattern during fear acquisition 'and' extinction for the BDNFval66met polymorphism using a differential conditioned stimulus (CS)+ > CS- comparison. During conditioning, we observed heightened allele dose-dependent responses in the amygdala and reduced responses in the subgenual anterior cingulate cortex in BDNFval66met met-carriers. During early extinction, 24h later, we again observed heightened responses in several regions ascribed to the fear network in met-carriers as opposed to val-carriers (insula, amygdala, hippocampus), which likely reflects fear memory recall. No differences were observed during late extinction, which likely reflects learned extinction. Our data thus support previous associations of the BDNFval66met polymorphism with neural activation in the fear and extinction network, but speak against a specific association with fear extinction processes.
authors.affiliation: Institute for Systems Neuroscience, University Hospital Hamburg-Eppendorf, Hamburg, Germany, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden, Stockholm Brain Institutet, Stockholm, Sweden, Department of Molecular Medicine and Surgery, Neurogenetics Section, Karolinska Institutet, Stockholm, Sweden, and Center for Molecular Medicine, Karolinska University Hospital, Solna, Sweden Institute for Systems Neuroscience, University Hospital Hamburg-Eppendorf, Hamburg, Germany, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden, Stockholm Brain Institutet, Stockholm, Sweden, Department of Molecular Medicine and Surgery, Neurogenetics Section, Karolinska Institutet, Stockholm, Sweden, and Center for Molecular Medicine, Karolinska University Hospital, Solna, Sweden Institute for Systems Neuroscience, University Hospital Hamburg-Eppendorf, Hamburg, Germany, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden, Stockholm Brain Institutet, Stockholm, Sweden, Department of Molecular Medicine and Surgery, Neurogenetics Section, Karolinska Institutet, Stockholm, Sweden, and Center for Molecular Medicine, Karolinska University Hospital, Solna, Sweden Institute for Systems Neuroscience, University Hospital Hamburg-Eppendorf, Hamburg, Germany, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden, Stockholm Brain Institutet, Stockholm, Sweden, Department of Molecular Medicine and Surgery, Neurogenetics Section, Karolinska Institutet, Stockholm, Sweden, and Center for Molecular Medicine, Karolinska University Hospital, Solna, Sweden t.lonsdorf@uke.de.
authors.forename: Tina B
authors.initials: TB
authors.lastname: Lonsdorf
authors.affiliation: Institute for Systems Neuroscience, University Hospital Hamburg-Eppendorf, Hamburg, Germany, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden, Stockholm Brain Institutet, Stockholm, Sweden, Department of Molecular Medicine and Surgery, Neurogenetics Section, Karolinska Institutet, Stockholm, Sweden, and Center for Molecular Medicine, Karolinska University Hospital, Solna, Sweden Institute for Systems Neuroscience, University Hospital Hamburg-Eppendorf, Hamburg, Germany, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden, Stockholm Brain Institutet, Stockholm, Sweden, Department of Molecular Medicine and Surgery, Neurogenetics Section, Karolinska Institutet, Stockholm, Sweden, and Center for Molecular Medicine, Karolinska University Hospital, Solna, Sweden.
authors.forename: Armita
authors.initials: A
authors.lastname: Golkar
authors.affiliation: Institute for Systems Neuroscience, University Hospital Hamburg-Eppendorf, Hamburg, Germany, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden, Stockholm Brain Institutet, Stockholm, Sweden, Department of Molecular Medicine and Surgery, Neurogenetics Section, Karolinska Institutet, Stockholm, Sweden, and Center for Molecular Medicine, Karolinska University Hospital, Solna, Sweden.
authors.forename: Kara M
authors.initials: KM
authors.lastname: Lindström
authors.affiliation: Institute for Systems Neuroscience, University Hospital Hamburg-Eppendorf, Hamburg, Germany, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden, Stockholm Brain Institutet, Stockholm, Sweden, Department of Molecular Medicine and Surgery, Neurogenetics Section, Karolinska Institutet, Stockholm, Sweden, and Center for Molecular Medicine, Karolinska University Hospital, Solna, Sweden Institute for Systems Neuroscience, University Hospital Hamburg-Eppendorf, Hamburg, Germany, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden, Stockholm Brain Institutet, Stockholm, Sweden, Department of Molecular Medicine and Surgery, Neurogenetics Section, Karolinska Institutet, Stockholm, Sweden, and Center for Molecular Medicine, Karolinska University Hospital, Solna, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Haaker
authors.affiliation: Institute for Systems Neuroscience, University Hospital Hamburg-Eppendorf, Hamburg, Germany, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden, Stockholm Brain Institutet, Stockholm, Sweden, Department of Molecular Medicine and Surgery, Neurogenetics Section, Karolinska Institutet, Stockholm, Sweden, and Center for Molecular Medicine, Karolinska University Hospital, Solna, Sweden Institute for Systems Neuroscience, University Hospital Hamburg-Eppendorf, Hamburg, Germany, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden, Stockholm Brain Institutet, Stockholm, Sweden, Department of Molecular Medicine and Surgery, Neurogenetics Section, Karolinska Institutet, Stockholm, Sweden, and Center for Molecular Medicine, Karolinska University Hospital, Solna, Sweden.
authors.forename: Arne
authors.initials: A
authors.lastname: Öhman
authors.affiliation: Institute for Systems Neuroscience, University Hospital Hamburg-Eppendorf, Hamburg, Germany, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden, Stockholm Brain Institutet, Stockholm, Sweden, Department of Molecular Medicine and Surgery, Neurogenetics Section, Karolinska Institutet, Stockholm, Sweden, and Center for Molecular Medicine, Karolinska University Hospital, Solna, Sweden Institute for Systems Neuroscience, University Hospital Hamburg-Eppendorf, Hamburg, Germany, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden, Stockholm Brain Institutet, Stockholm, Sweden, Department of Molecular Medicine and Surgery, Neurogenetics Section, Karolinska Institutet, Stockholm, Sweden, and Center for Molecular Medicine, Karolinska University Hospital, Solna, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Schalling
authors.affiliation: Institute for Systems Neuroscience, University Hospital Hamburg-Eppendorf, Hamburg, Germany, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden, Stockholm Brain Institutet, Stockholm, Sweden, Department of Molecular Medicine and Surgery, Neurogenetics Section, Karolinska Institutet, Stockholm, Sweden, and Center for Molecular Medicine, Karolinska University Hospital, Solna, Sweden Institute for Systems Neuroscience, University Hospital Hamburg-Eppendorf, Hamburg, Germany, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden, Stockholm Brain Institutet, Stockholm, Sweden, Department of Molecular Medicine and Surgery, Neurogenetics Section, Karolinska Institutet, Stockholm, Sweden, and Center for Molecular Medicine, Karolinska University Hospital, Solna, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Ingvar
mesh_terms: D000328:Adult; D001007:Anxiety / Q000235:genetics / Q000523:psychology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000502:physiology*; D003213:Conditioning, Psychological / Q000502:physiology*; D005108:Extinction, Psychological / Q000502:physiology; D005239:Fear / Q000502:physiology*; D005260:Female; D005712:Galvanic Skin Response / Q000502:physiology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D011939:Mental Recall / Q000502:physiology*; D009154:Mutation / Q000235:genetics* / Q000502:physiology*; D010100:Oxygen / Q000097:blood; D010775:Photic Stimulation; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D010100:Oxygen
keywords: CBT; amygdala; anxiety; fear recall; therapygenetics; vmPFC
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