COMT Val158Met polymorphism moderates the association between PTSD symptom severity and hippocampal volume

Hayes, Jasmeet P.; Logue, Mark W.; Reagan, Andrew J.; Salat, David H.; Wolf, Erika J.; Sadeh, Naomi; Spielberg, Jeffrey M.; Sperbeck, Emily; Hayes, Susan L.; McGlinchey, Regina E.; Milberg, William; Verfaellie, Mieke; Stone, Annjanette; Schichman, Steven A.; Miller, Mark W.

doi:10.1503/jpn.150339

Cited by 21 publications

(15 citation statements)

References 72 publications

(73 reference statements)

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“…The PTSD has been associated with BDNF genotype, particularly the Val66Met polymorphism (Dretsch et al 2016;Felmingham et al 2013), although there is currently a lack of evidence of a PTSD by BDNF genotype interaction on hippocampal volume. It may be that other candidate genes are more closely tied to smaller hippocampal volumes in PTSD, as recently reported by Hayes et al (2017a). In this study, PTSD symptom severity interacted with COMT to predict reduced hippocampal volume, i.e.…”

Section: Discussionsupporting

confidence: 73%

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BDNF genotype is associated with hippocampal volume in mild traumatic brain injury

Hayes

Reagan

Logue

et al. 2017

Genes Brain and Behavior

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The negative long-term effects of mild traumatic brain injury (mTBI) have been a growing concern in recent years, with accumulating evidence suggesting that mTBI combined with additional vulnerability factors may induce neurodegenerative-type changes in the brain. However, the factors instantiating risk for neurodegenerative disease following mTBI are unknown. This study examined the link between mTBI and brain-derived neurotrophic factor (BDNF) genotype, which has previously been shown to regulate processes involved in neurodegeneration including synaptic plasticity and facilitation of neural survival through its expression. Specifically, we examined nine BDNF single-nucleotide polymorphisms (SNPs; rs908867, rs11030094, rs6265, rs10501087, rs1157659, rs1491850, rs11030107, rs7127507 and rs12273363) previously associated with brain atrophy or memory deficits in mTBI. Participants were 165 white, non-Hispanic Iraq and Afghanistan war veterans between the ages of 19 and 58, 110 of whom had at least one mTBI in their lifetime. Results showed that the BDNF SNP rs1157659 interacted with mTBI to predict hippocampal volume. Furthermore, exploratory analysis of functional resting state data showed that rs1157659 minor allele homozygotes with a history of mTBI had reduced functional connectivity in the default mode network compared to major allele homozygotes and heterozygotes. Apolipoprotein E (APOE) was not a significant predictor of hippocampal volume or functional connectivity. These results suggest that rs1157659 minor allele homozygotes may be at greater risk for neurodegeneration after exposure to mTBI and provide further evidence for a potential role for BDNF in regulating neural processes following mTBI.

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Section: Discussionsupporting

confidence: 73%

“…It may be that other candidate genes are more closely tied to smaller hippocampal volumes in PTSD, as recently reported by Hayes et al . (). In this study, PTSD symptom severity interacted with COMT to predict reduced hippocampal volume, i.e.…”

Section: Discussionmentioning

confidence: 97%

BDNF genotype is associated with hippocampal volume in mild traumatic brain injury

Hayes

Reagan

Logue

et al. 2017

Genes Brain and Behavior

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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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Prominent genetic variants and epigenetic changes in post-traumatic stress disorder among combat veterans

Baghaei,

Zoshk,

Hosseini

et al. 2024

Mol Biol Rep

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COMT Val158Met polymorphism moderates the association between PTSD symptom severity and hippocampal volume

Cited by 21 publications

References 72 publications

BDNF genotype is associated with hippocampal volume in mild traumatic brain injury

BDNF genotype is associated with hippocampal volume in mild traumatic brain injury

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

Prominent genetic variants and epigenetic changes in post-traumatic stress disorder among combat veterans

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