Archival Report| Volume 73, ISSUE 11, P1059-1063, June 01, 2013

The Brain-Derived Neurotrophic Factor Val66Met Polymorphism Predicts Response to Exposure Therapy in Posttraumatic Stress Disorder


      The most effective treatment for posttraumatic stress disorder (PTSD) is exposure therapy, which aims to facilitate extinction of conditioned fear. Recent evidence suggests that brain-derived neurotrophic factor (BDNF) facilitates extinction learning. This study assessed whether the Met-66 allele of BDNF, which results in lower activity-dependent secretion, predicts poor response to exposure therapy in PTSD.


      Fifty-five patients with PTSD underwent an 8-week exposure-based cognitive behavior therapy program and provided mouth swabs or saliva to extract genomic DNA to determine their BDNF Val66Met genotype (30 patients with the Val/Val BDNF allele, 25 patients with the Met-66 allele). We examined whether BDNF genotype predicted reduction in PTSD severity following exposure therapy.


      Analyses revealed poorer response to exposure therapy in the PTSD patients with the Met-66 allele of BDNF compared with patients with the Val/Val allele. Pretreatment Clinician Administered PTSD Scale severity and BDNF Val66Met polymorphism predicted response to exposure therapy using hierarchical regression.


      This study provides the first evidence that the BDNF Val66Met genotype predicts response to cognitive behavior therapy in PTSD and is in accord with evidence that BDNF facilitates extinction learning.

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      Linked Article

      • The First Steps on the Path Toward Genomic Predictors of Behavioral Therapy for Posttraumatic Stress Disorder
        Biological PsychiatryVol. 73Issue 11
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          Not everyone who has personally experienced, or has been exposed to, severe trauma develops posttraumatic stress disorder (PTSD). The risk-resilience equation is complex and, as we are becoming increasingly aware, includes both genetic predictors and environmental stressors, starting in early childhood. For example, as Binder and colleagues (1) first showed, FKBP5, a gene influencing activity of the hypothalamic-pituitary-adrenal axis, together with exposure to childhood trauma but not adult stressors, predicted the development of PTSD in a low-income, urban African American sample.
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