The BDNF Val66Met polymorphism affects negative memory bias in civilian women with PTSD

Hiroaki Hori,Yuko Hakamata,Toshiko Kamo,Madoka Niwa,Mariko Itoh,Keiko Ino,Mie Matsui,Yoshiharu Kim,Risa Imai,Hiroshi Kunugi,Mingming Lin,Fuyuko Yoshida,Sei Ogawa

doi:10.1038/s41598-020-60096-1

Abstract

Memory abnormalities are considered a core feature of posttraumatic stress disorder (PTSD). Studies attempting to quantify such memory dysfunction in PTSD have reported that individuals with this disorder exhibit selective memory bias toward negative material. The low expression Met allele of brain-derived neurotrophic factor (BDNF) Val66Met polymorphism has been associated with the aetiology of PTSD and with memory abnormalities. It is therefore possible that the BDNF Val66Met polymorphism can moderate the relationship between PTSD and memory bias. Here we examined this association in 50 civilian women with PTSD and 70 non-trauma-exposed healthy control women. All subjects were genotyped for the BDNF Val66Met (rs6265) polymorphism. Negative memory bias was assessed using a recognition memory task. Patients showed significantly greater negative memory bias compared to controls. In patients, negative memory bias significantly increased with increasing numbers of Met alleles; while no significant relationship was seen in controls. Further pairwise analyses revealed that patients with the Met allele had significantly greater negative memory bias than controls. These results suggest that the relationship between PTSD and negative memory bias can be moderated by the BDNF Val66Met polymorphism. More studies are needed to further clarify the relationship between this polymorphism and memory abnormalities in PTSD.

Highlights

Memory abnormalities are considered a core feature of posttraumatic stress disorder (PTSD)
This study aimed to examine the association of the brainderived neurotrophic factor (BDNF) Val66Met polymorphism with memory bias in civilian women with PTSD and healthy control women
This study, which extends our previous finding of memory bias[5], is the first, to our knowledge, to investigate the association between the BDNF Val66Met polymorphism and memory bias in PTSD

Summary

Introduction

Memory abnormalities are considered a core feature of posttraumatic stress disorder (PTSD). Further pairwise analyses revealed that patients with the Met allele had significantly greater negative memory bias than controls These results suggest that the relationship between PTSD and negative memory bias can be moderated by the BDNF Val66Met polymorphism. Using a mouse model with the humanized BDNF Val66Met polymorphism knocked-in, it was shown that chronic activation of glucocorticoid receptors during late adolescence increases fear memory in adulthood according to the Val66Met genotype[14] This finding suggests that chronic stress potentiates the fear circuitry into adulthood in the Met carriers, thereby increasing their susceptibility to fear- and anxiety-related psychiatric disorders such as PTSD8,14. A human study demonstrated that PTSD patients with the Met allele exhibit impaired fear extinction learning compared to those with the Val/Val genotype, suggesting that this polymorphism can cause memory abnormalities in this disorder[18]. No studies to date have examined its relationship with memory bias in PTSD

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