Influence of childhood trauma and brain-derived neurotrophic factor Val66Met polymorphism on posttraumatic stress symptoms and cortical thickness

Jin, Min; Jeon, Hong Jun; Hyun, Myoung Ho; Lee, Seung Hwan

doi:10.1038/s41598-019-42563-6

Cited by 27 publications

(23 citation statements)

References 91 publications

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“…Genetic studies for PTSD are useful to identify risk factors for the development of the disorder and improve its treatment 20 , and BDNF is considered a relevant candidate gene for PTSD [6][7][8]21 . Supporting this, previous studies have shown that Met allele carriers of the BDNF Val66Met polymorphism, compared to Val/Val homozygotes, www.nature.com/scientificreports www.nature.com/scientificreports/ have impaired fear extinction learning 18 and poorer response to exposure therapy 22 .…”

Section: Discussionmentioning

confidence: 99%

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

Hori

Itoh

Yoshida

et al. 2020

Sci Rep

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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...

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Section: Discussionmentioning

confidence: 99%

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

Hori

Itoh

Yoshida

et al. 2020

Sci Rep

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“…The SNP in the gene BDNF, BDNFVal66Met, is one example, among many, of an interesting candidate to explore for influencing chemotherapeutic impact and secondary effects across development. This SNP in the BDNF gene has been associated with altered susceptibility to a variety of neuropsychiatric disorders including anxiety and depression in adults (Frielingsdorf et al, 2010; Gatt et al, 2009; Gratacos et al, 2007; Jiang et al, 2005; Momose et al, 2002; Sen et al, 2003; Sklar et al, 2002; Ventriglia et al, 2002) and more recently has been shown to influence PTSD symptoms and cortical thickness in childhood trauma (Jin et al, 2019). This valine-to-methionine substitution at position 66 of the BDNF prodomain alters normal interactions with the sorting protein, sortilin, resulting in altered trafficking of BDNF into the regulated secretory pathway, which leads to an approximate 30% decrease in activity-dependent release (Chen et al, 2005, 2006; Chen et al, 2004; Egan et al, 2003).…”

Section: Genetic Influences To Consider For Effects Of Cancer Treatmementioning

confidence: 99%

Future considerations for pediatric cancer survivorship: Translational perspectives from developmental neuroscience

Jones

Pattwell

2019

Developmental Cognitive Neuroscience

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Breakthroughs in modern medicine have increased pediatric cancer survival rates throughout the last several decades. Despite enhanced cure rates, a subset of pediatric cancer survivors exhibit life-long psychological side effects. A large body of work has addressed potential mechanisms for secondary symptoms of anxiety, post-traumatic stress, impaired emotion regulation and cognitive deficits in adults. Yet, absent from many studies are the ways in which cancer treatment can impact the developing brain. Additionally, it remains less known whether typical neurobiological changes during adolescence and early adulthood may potentially buffer or exacerbate some of the known negative cancer survivorship outcomes. This review highlights genetic, animal, and human neuroimaging research across development. We focus on the neural circuitry associated with aversive learning, which matures throughout childhood, adolescence and early adulthood. We argue that along with other individual differences, the precise timing of oncological treatment insults on such neural circuitry may expose particular vulnerabilities for pediatric cancer patients. We also explore other moderators of treatment outcomes, including genetic polymorphisms and neural mechanisms underlying memory and cognitive control. We discuss how neural maturation extending into young adulthood may also provide a sensitive period for intervention to improve psychological and cognitive outcomes in pediatric cancer survivors.

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“…One way to alleviate the clinical heterogeneity of PTSD is to take advantage of intermediate phenotypes, especially the quantitative neuroimaging phenotypes [26][27][28] . A growing body of imaging genetics research has proven the association between neuroimaging measures and candidate genes in PTSD [29][30][31] . Catechol-O-methyltransferase (COMT) Val 158 Met (rs4680) and brain-derived neurotrophic factor (BDNF) Val 66 Met (rs6265) polymorphisms are two typical and well-described genetic variants that have been proven to be associated with stress response and resilience [32][33][34] .…”

Section: Introductionmentioning

confidence: 99%

“…Catechol-O-methyltransferase (COMT) Val 158 Met (rs4680) and brain-derived neurotrophic factor (BDNF) Val 66 Met (rs6265) polymorphisms are two typical and well-described genetic variants that have been proven to be associated with stress response and resilience [32][33][34] . These two genetic variants have been extensively investigated in populations consisting of healthy subjects 33,35 and those with anxiety disorders 36,37 , including PTSD 29,31 . Meanwhile, both COMT rs4680 and BDNF rs6265 regulate the brain dopamine system 38 -an important system in the pathogenesis of PTSD-by their important role in regulating fear memory emotion and behaviors.…”

Section: Introductionmentioning

confidence: 99%

“…BDNF is a key neurotrophin that regulates neuronal plasticity, neuronal survival, and neurogenesis, and the Met 66 allele of BDNF rs6265 polymorphism is associated with lower BDNF release compared with the Val 66 allele, resulting in reduced activity-dependent dopamine release 43 . Both COMT rs4680 and BDNF rs6265 polymorphisms are suggested to moderate several neuroimaging structural phenotypes observed in PTSD 29,31,44 . In addition, recently, the interaction effect between COMT rs4680 and BDNF rs6265 on brain function has been reported in healthy subjects 45,46 .…”

Section: Introductionmentioning

confidence: 99%

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Effects of COMT rs4680 and BDNF rs6265 polymorphisms on brain degree centrality in Han Chinese adults who lost their only child

Luo

Zhang

et al. 2020

Transl Psychiatry

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Losing one's only child is a major traumatic life event that may lead to posttraumatic stress disorder (PTSD); however, not all parents who experience this trauma develop PTSD. Genetic variants are associated with the risk of developing PTSD. Catechol-O-methyltransferase (COMT) rs4680 and brain-derived neurotrophic factor (BDNF) rs6265 are two most well-described single-nucleotide polymorphisms that relate to stress response; however, the neural mechanism underlying their effects on adults who lost an only child remains poorly understood. Two hundred and ten Han Chinese adults who had lost their only child (55 with PTSD and 155 without PTSD) were included in this imaging genetics study. Participants were divided into subgroups according to their COMT rs4680 and BDNF rs6265 genotypes. Degree Centrality (DC)-a resting-state fMRI index reflecting the brain network communication-was compared with a three-way (PTSD diagnosis, COMT, and BDNF polymorphisms) analysis of covariance. Diagnosis state had a significant effect on DC in bilateral inferior parietal lobules and right middle frontal gyrus (MFG), where PTSD adults showed weaker DC. BDNF × diagnosis interaction effect was found in the right MFG and hippocampus, and these two regions were reversely modulated. Also, there was a significant COMT × BDNF interaction effect in left cuneus, middle temporal gyrus, right inferior occipital gyrus, and bilateral putamen, independent of PTSD diagnosis. These findings suggest that the modulatory effect of BDNF polymorphism on the MFG and hippocampus may contribute to PTSD development in bereaved adults. Interactions of COMT × BDNF polymorphisms modulate some cortices and basal ganglia, irrespective of PTSD development.

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Influence of childhood trauma and brain-derived neurotrophic factor Val66Met polymorphism on posttraumatic stress symptoms and cortical thickness

Cited by 27 publications

References 91 publications

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

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

Future considerations for pediatric cancer survivorship: Translational perspectives from developmental neuroscience

Effects of COMT rs4680 and BDNF rs6265 polymorphisms on brain degree centrality in Han Chinese adults who lost their only child

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