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

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 brainderived 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.Posttraumatic stress disorder (PTSD) is a serious psychiatric condition that can develop after a major traumatic event, often leading to a chronic course and severe functional impairment. Among various psychobehavioural symptoms of PTSD, involuntary retrieval of traumatic memories that are collectively termed as "re-experiencing" symptoms, such as intrusive thoughts, flashbacks, and nightmares, are postulated as a central feature of this disorder. The presence of these re-experiencing phenomena suggests that trauma-related fear can be easily activated in these individuals even in the absence of an actual threat, and this sense of threat is considered to arise, at least in part, as a consequence of excessively negative appraisals of the trauma and its sequelae 1 .One approach to quantifying such disordered memory/cognition in PTSD is to experimentally measure selective memory bias toward negative and/or emotionally threatening material. To date, a number of studies have observed the memory bias in individuals with this disorder compared to healthy controls 2-4 . We have also found that female patients with PTSD as a group display negative memory bias, albeit with considerable inter-individual variation 5 . Such variation in negative memory bias may be related to the heterogeneous nature of this disorder.Evidence suggests that genetic factors are involved in the aetiology of PTSD 6 . Based on both biological mechanisms and data-driven approaches, the brain-derived neurotrophic factor (BDNF) gene is considered as one of the most relevant candidate genes for this disorder [6][7][8][9][10][11] . BDNF encodes a neurotr...

Association of Brain‐Derived Neurotrophic Factor rs6265 G>A polymorphism and Post‐traumatic Stress Disorder susceptibility: A systematic review and meta‐analysis

“…Finally, 16 studies with 1,739 patients and 3,630 controls met the inclusion and exclusion criteria (Bruenig et al., 2016; Dai et al., 2017; Dretsch et al., 2016; Guo et al., 2018, 2019; Heon‐Jeong et al., 2006; Hori et al., 2020; Jin et al., 2019; Li et al., 2016; Lyoo et al., 2011; Pivac et al., 2012; Qi et al., 2020; Valente et al., 2011; Young et al., 2018; Zhang et al., 2006, 2014). There were four studies in Caucasian populations (Bruenig et al., 2016; Pivac et al., 2012; Young et al., 2018; Zhang et al., 2006), nine studies in Asian populations (Dai et al., 2017; Guo et al., 2018, 2019; Heon‐Jeong et al., 2006; Hori et al., 2020; Jin et al., 2019; Li et al., 2016; Lyoo et al., 2011; Qi et al., 2020), and three studies in mixed populations (Dretsch et al., 2016; Valente et al., 2011; Zhang et al., 2014). Five studies used the polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) method, while the rest used real‐time PCR, TaqMan, SnaPShot, Sequencer platform, and Illumina methods.…”

“…In knock‐in mice, extinction learning was impaired in Met allele carriers compared to non‐Met allele carriers (Soliman et al., 2010); there was a similar finding in patients with PTSD with the Met allele when compared to those with the Val allele (Felmingham et al., 2018). A human study by Horri et al revealed that PTSD patients with the Met allele had significantly worse memory performance than controls, indicating that the rs6265 polymorphism could be involved more in core memory abnormalities than general memory dysfunction in PTSD (Hori et al., 2020).…”

Childhood maltreatment history and attention bias variability in healthy adult women: role of inflammation and the BDNF Val66Met genotype

“…Second, as we only included female participants, it is unknown whether the present findings might be specific to women or common to both sexes. The main reason for the focus on female patients was that this study built on our previous studies of childhood maltreatment, cognitive function, memory bias, inflammation, and the BDNF Val66Met polymorphism in women with PTSD 61,[92][93][94] . In addition, it was necessary to consider potential sex differences in this study, given the evidence for differential psychobiological impacts of childhood maltreatment between sexes 95 and for sexually dimorphic effects of the BDNF Val66Met polymorphism 49 .…”

“…This SNP has also been associated with attention bias 56 , 57 and circulating inflammatory markers 58 , 59 . Furthermore, this SNP has been associated with exaggerated expression of memories with negative emotional valence in both mice 60 and human PTSD patients 61 . These findings together suggest that the BDNF Val66Met polymorphism may affect attention bias and ABV by interacting with childhood maltreatment.…”

Moderating Effects of BDNF Genetic Variants and Smoking on Cognition in PTSD Veterans

“…The presence of the A allele was associated with greater severity of lifetime and current PTSD symptoms in a large number of European American U.S. military veterans [ 53 ]. The A carriers had reduced competence in judging their spatial processing of navigation performance [ 54 ], negative memory bias [ 55 ], higher re-experiencing symptoms [ 53 ], elevated hyperarousal vulnerability, and increased startle scores [ 56 ], compared to GG genotype carriers. In our previous study that included a smaller number of war veterans with or without PTSD, we have detected significant association between cognition (visual-spatial perception and short and long-term visual memory function) determined using the Rey-Osterrieth Complex Figure (ROCF) test and BDNF rs6265 in war veterans with PTSD [ 11 ].…”