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

School of Psychology (KLF), University of Tasmania, Hobart
Biological psychiatry (Impact Factor: 10.26). 01/2013; 73(11). DOI: 10.1016/j.biopsych.2012.10.033
Source: PubMed


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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Available from: Kim Felmingham, Oct 13, 2015
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    • "The authors concluded that met-alleles showed behavioral resistance towards exposure therapy in PTSD compared to val66val. They also suggested met-allele as a genetic predictor of exposure therapy in PTSD (Felmingham et al., 2013). The present finding suggests that the coupling of memory reconsolidation and exposure therapy in healthy subjects with the met-allele may be responsible for diminishing spontaneous recovery, further accounting for the discrepant research findings in memory reconsolidation (Chan et al., 2010;Golkar et al., 2012;Kindt and Soeter, 2013;Wood et al., 2015). "

    Full-text · Article · Dec 2015 · The International Journal of Neuropsychopharmacology
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    • " stages in children and adolescents ( Huemer et al . 2010 ) . Furthermore , future work should ascertain how sex differences interact with developmental stages across the lifespan . Several genes are associated with an increased risk for PTSD and other anxiety disorders ( Almli et al . 2014 ; El - Kordi et al . 2013 ; Erhardt and Spoormaker 2013 ; Felmingham et al . 2013 ; Norrholm et al . 2013 ; Wilker et al . 2013 ) , and these genes may also predispose individuals to relapse . In addition , epigenetic mechanisms of stress and psychopathology have received considerable attention in recent years ( Maddox et al . 2013 ; Norrholm et al . 2013 ; Zovkic et al . 2013 ) , and these factors might also confer "
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    ABSTRACT: Whereas fear memories are rapidly acquired and enduring over time, extinction memories are slow to form and are susceptible to disruption. Consequently, behavioral therapies that involve extinction learning (e.g., exposure therapy) often produce only temporary suppression of fear and anxiety. This review focuses on the factors that are known to influence the relapse of extinguished fear. Several phenomena associated with the return of fear after extinction are discussed, including renewal, spontaneous recovery, reacquisition, and reinstatement. Additionally, this review describes recent work, which has focused on the role of psychological stress in the relapse of extinguished fear. Recent developments in behavioral and pharmacological research are examined in light of treatment of pathological fear in humans.
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    • "Interestingly, a recent study in humans and rats suggests that BDNF over-expression may be a critical stress response underlying PTSD by showing that the Val66Met allele confers vulnerability to PTSD via startle data and plasma BDNF levels (Zhang et al., 2013). Furthermore, BDNF polymorphisms may be associated with response to treatment (Felmingham et al., 2013), consistent with its known role in mechanisms of extinction of fear. Studies combining neuroimaging with genetics may shed more light on the association with BDNF and PTSD. "
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    ABSTRACT: Post-traumatic stress disorder (PTSD) is increasingly recognized as both a disorder of enormous mental health and societal burden, but also as an anxiety disorder that may be particularly understandable from a scientific perspective. Specifically, PTSD can be conceptualized as a disorder of fear and stress dysregulation, and the neural circuitry underlying these pathways in both animals and humans are becoming increasingly well understood. Furthermore, PTSD is the only disorder in psychiatry in which the initiating factor, the trauma exposure, can be identified. Thus, the pathophysiology of the fear and stress response underlying PTSD can be examined and potentially interrupted. Twin studies have shown that the development of PTSD following a trauma is heritable, and that genetic risk factors may account for up to 30-40% of this heritability. A current goal is to understand the gene pathways that are associated with PTSD, and how those genes act on the fear/stress circuitry to mediate risk vs. resilience for PTSD. This review will examine gene pathways that have recently been analysed, primarily through candidate gene studies (including neuroimaging studies of candidate genes), in addition to genome-wide associations and the epigenetic regulation of PTSD. Future and on-going studies are utilizing larger and collaborative cohorts to identify novel gene candidates through genome-wide association and other powerful genomic approaches. Identification of PTSD biological pathways strengthens the hope of progress in the mechanistic understanding of a model psychiatric disorder and allows for the development of targeted treatments and interventions.
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