Volume 1208, Issue 1 p. 150-157

Variant brain-derived neurotrophic factor Val66Met endophenotypes: implications for posttraumatic stress disorder

Helena Frielingsdorf

Helena Frielingsdorf

The Sackler Institute for Developmental Psychobiology, Weill Medical College of Cornell University, New York, New York.

Department of Psychiatry, Weill Medical College of Cornell University, New York, New York

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Kevin G. Bath

Kevin G. Bath

The Sackler Institute for Developmental Psychobiology, Weill Medical College of Cornell University, New York, New York.

Department of Psychiatry, Weill Medical College of Cornell University, New York, New York

Department of Neuroscience, Brown University, Providence, Rhode Island

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Fatima Soliman

Fatima Soliman

The Sackler Institute for Developmental Psychobiology, Weill Medical College of Cornell University, New York, New York.

Department of Psychiatry, Weill Medical College of Cornell University, New York, New York

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JoAnn DiFede

JoAnn DiFede

Department of Psychiatry, Weill Medical College of Cornell University, New York, New York

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B. J. Casey

B. J. Casey

The Sackler Institute for Developmental Psychobiology, Weill Medical College of Cornell University, New York, New York.

Department of Psychiatry, Weill Medical College of Cornell University, New York, New York

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Francis S. Lee

Francis S. Lee

Department of Psychiatry, Weill Medical College of Cornell University, New York, New York

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First published: 18 October 2010
Citations: 106
Address for correspondence: Helena Frielingsdorf or Francis S. Lee, Department of Psychiatry, Weill Cornell Medical College, 1300 York Avenue, Box 244, New York, New York 10065. [email protected] or [email protected]

Abstract

Recently, a common single nucleotide polymorphism (SNP) has been identified in the gene encoding brain-derived neurotrophic factor (BDNF). The variant BDNFMet has been shown to have decreased activity-dependent BDNF secretion from neurons and to lead to impairments in specific forms of learning and altered susceptibility to stress. A mouse model containing BDNFMet has also been linked to increased anxiety-like behavior. In a translational study, mice and human carriers of the BDNFMet allele were compared in their ability to extinguish a learned fear memory. Both showed slower suppression of the learned fear response. In humans, the neural correlates of this behavior were validated using fMRI. As anxiety and fear extinction lie at the core of symptoms and therapeutic approaches to posttraumatic stress disorder (PTSD), we propose that BDNF genotype and neuroimaging may be useful as biomarkers to provide guidance for more customized therapeutic directions. The aim of this paper is to review the available knowledge on the BDNF Val66Met SNP, with emphasis on anxiety- and fear-related endophenotypes and its potential implications for PTSD.