PTSD risk is associated with BDNF Val66Met and BDNF overexpression

Zhang, L; Benedek, David M.; Fullerton, Carol S.; Forsten, Robert D.; Naifeh, James A.; Li, X X; Hu, X Z; Li, H; Jia, Min; Xing, Guoqiang; Benevides, K. Nikki; Ursano, Robert J.

doi:10.1038/mp.2012.180

Cited by 121 publications

(127 citation statements)

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“…15 The BDNF Val66Met SNP reduces activity-dependent secretion of BDNF 16 without affecting constitutive secretion or mature levels of the peptide, and leads to alterations in the dendritic complexity of hippocampal neurons and total hippocampal volume. 17 This SNP has been associated with anxiety, 17 hypothalamic-pituitary-adrenal axis reactivity to stress, 18,19 depression, 20 posttraumatic stress disorder, 21 and substance abuse. 22 The importance of the Val66Met SNP and nicotine dependence remains unclear as studies report conflicting results on the association between the SNP and smoking behavior.…”

mentioning

confidence: 99%

Effects of the BDNF Val66Met Polymorphism on Anxiety-Like Behavior Following Nicotine Withdrawal in Mice

Lee

Anastasía

Hempstead

et al. 2015

NICTOB

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confidence: 99%

Effects of the BDNF Val66Met Polymorphism on Anxiety-Like Behavior Following Nicotine Withdrawal in Mice

Lee

Anastasía

Hempstead

et al. 2015

NICTOB

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“…The related studies were conducted in adults among European (Croatia), Asian (South Korea) and American populations (USA and Brazil). In detail, 3 articles [16,19,26] involved healthy individuals as controls, and another 2 papers [14,17] used people who suffered from the same stress as cases but without PTSD symptoms - 1 article [18 ]contained both types of controls and thus were treated separately as 2 studies. In addition, 2 articles [14,17] examined PTSD participants who were exposed to stress/traumatic events from active duty in the army.…”

Section: Resultsmentioning

confidence: 99%

“…During each stage of screening, the literature articles were clearly identified and a consensus could be established. Finally, 6 articles [14,16,17,18,19,26] were selected. Articles in each selection step are shown in online supplementary figure S1.…”

Section: Resultsmentioning

confidence: 99%

“…A total of 87 publications were produced by our search strategy from the three aforementioned online databases at the initial stage; 2 articles [14,26] were yielded by manual search from the bibliographies of reviews. During each stage of screening, the literature articles were clearly identified and a consensus could be established.…”

Section: Resultsmentioning

confidence: 99%

“…Clinical observations also support that the BDNF Val66Met variant [13] plays a role in PTSD. However, contradictory findings were found in the association studies [14,15,16,17,18,19]. Therefore, we conducted this analysis to estimate the influence of BDNF Val66Met on the risk of PTSD.…”

Section: Introductionmentioning

confidence: 99%

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Does<b><i> BDNF</i></b> Val66Met Polymorphism Confer Risk for Posttraumatic Stress Disorder?

Wang¹

2015

Neuropsychobiology

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Background: Evidence has indicated that BDNF (brain-derived neurotrophic factor) Val66Met genetic variant could be linked to the development of posttraumatic stress disorder (PTSD). However, clinical observations studying the BDNF polymorphism and the risk of PTSD yielded contradictory results. In this meta-analysis we evaluated the association between BDNF Val66Met and PTSD risk. Method: Systematic searches in online databases retrieved 6 relevant publications. Different inherited models were utilized to perform the pooled analysis. Subgroup analyses and sensitive analyses based on Hardy-Weinberg equilibrium (HWE) test results were also carried out. Results: Our study did not found a significant overall effect of BDNF Val66Met on the susceptibility to PTSD under various genetic models. In contrast, subgroup analyses suggested that the stress status of the control group, but not ethnicity, may influence the relationship of BDNF Val66Met with PTSD risk. After the exclusion of a study that was not in HWE, our conclusions remained unchanged during the influence analyses. Conclusions: This meta-analysis suggested no genetic association of BDNF Val66Met with vulnerability to PTSD. Further research studies are warranted to clarify the impact of BDNF variants on the occurrence of PTSD.

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Methionine increases BDNF DNA methylation and improves memory in epilepsy

Parrish

Buckingham

Mascia

et al. 2015

Ann Clin Transl Neurol

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ObjectiveTemporal lobe epilepsy (TLE) patients exhibit signs of memory impairments even when seizures are pharmacologically controlled. Surprisingly, the underlying molecular mechanisms involved in TLE-associated memory impairments remain elusive. Memory consolidation requires epigenetic transcriptional regulation of genes in the hippocampus; therefore, we aimed to determine how epigenetic DNA methylation mechanisms affect learning-induced transcription of memory-permissive genes in the epileptic hippocampus.MethodsUsing the kainate rodent model of TLE and focusing on the brain-derived neurotrophic factor (Bdnf) gene as a candidate of DNA methylation-mediated transcription, we analyzed DNA methylation levels in epileptic rats following learning. After detection of aberrant DNA methylation at the Bdnf gene, we investigated functional effects of altered DNA methylation on hippocampus-dependent memory formation in our TLE rodent model.ResultsWe found that behaviorally driven BdnfDNA methylation was associated with hippocampus-dependent memory deficits. Bisulfite sequencing revealed that decreased BdnfDNA methylation levels strongly correlated with abnormally high levels of BdnfmRNA in the epileptic hippocampus during memory consolidation. Methyl supplementation via methionine (Met) increased BdnfDNA methylation and reduced BdnfmRNA levels in the epileptic hippocampus during memory consolidation. Met administration reduced interictal spike activity, increased theta rhythm power, and reversed memory deficits in epileptic animals. The rescue effect of Met treatment on learning-induced BdnfDNA methylation, Bdnf gene expression, and hippocampus-dependent memory, were attenuated by DNA methyltransferase blockade.InterpretationOur findings suggest that manipulation of DNA methylation in the epileptic hippocampus should be considered as a viable treatment option to ameliorate memory impairments associated with TLE.

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PTSD risk is associated with BDNF Val66Met and BDNF overexpression

Cited by 121 publications

References 10 publications

Effects of the BDNF Val66Met Polymorphism on Anxiety-Like Behavior Following Nicotine Withdrawal in Mice

Effects of the BDNF Val66Met Polymorphism on Anxiety-Like Behavior Following Nicotine Withdrawal in Mice

Does<b><i> BDNF</i></b> Val66Met Polymorphism Confer Risk for Posttraumatic Stress Disorder?

Methionine increases BDNF DNA methylation and improves memory in epilepsy

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