The Influence of the Val66Met Polymorphism of Brain-Derived Neurotrophic Factor on Neurological Function after Traumatic Brain Injury

Finan, John D.; Udani, Shreya; Patel, Vimal; Bailes, Julian E.

doi:10.3233/jad-180585

Cited by 22 publications

(18 citation statements)

References 113 publications

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“…This suggests a shift in balance between the two forms of BDNF toward a more proapoptotic effect mediated by proBDNF, which may be particularly detrimental to patients with advanced age like those in the current patient cohort. Since the Val66Met genotype is associated with reduced activity-dependent secretion of both pro- and mature BDNF, it is conceivable that carrying the Met allele affords protection against cancer-related fatigue by reducing the proapoptotic effects of proBDNF 48 . It is worth noting that the protective advantage of Val66Met is likely to be genetic rather than a result of altered physical activity, as we did not observe any difference in daily activity between genotypes (Supplementary Fig.…”

Section: Discussionmentioning

confidence: 99%

Brain-derived neurotrophic factor polymorphism Val66Met protects against cancer-related fatigue

et al. 2020

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Cancer-related fatigue is an extremely common and debilitating psychiatric symptom that affects up to 80% of cancer patients. Despite its negative impact on the patient’s quality of life, there is no well-established biomarker or mechanisms associated with this debilitating condition. The functional brain-derived neurotrophic factor (BDNF) Val66Met single nucleotide polymorphism (SNP) has been associated with a variety of psychiatric illnesses. We hypothesized that Val66Met may influence the risk for developing cancer-related fatigue. BDNF Val66Met was analyzed by polymerase chain reaction in 180 patients with confirmed cancer diagnoses. Fatigue was measured using the Functional Assessment of Cancer Therapy-Fatigue (FACIT-Fatigue) questionnaire. Depression was measured using the Hamilton Depression Scale (HAM-D). Data were transformed when necessary and regression models were constructed to access the association between genotype and symptom severity. Participants carrying the Met allele reported significantly less fatigue compared to the Val/Val genotype group. The presence of the Met allele did not influence depression levels. The results suggest that the BDNF Val66Met polymorphism confers protective advantage against cancer-related fatigue; whereas having the Val/Val genotype may be a genetic risk factor. Findings from this study not only provide clues to the neural basis of cancer-related fatigue, but also allow for symptom severity prediction and patient education with the goal to improve symptom management.

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Section: Discussionmentioning

confidence: 99%

Brain-derived neurotrophic factor polymorphism Val66Met protects against cancer-related fatigue

et al. 2020

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“…Risk for confounding factors. (Finan et al 2018) [ 151 ] BDNF rs6265 The effect of the Met-allele depends on time point after TBI. Early evaluation, negative impact on cognition while protective effect of cognition at a later timing (years).…”

Section: Table A1mentioning

confidence: 99%

The Role of BDNF in Experimental and Clinical Traumatic Brain Injury

Gustafsson

Klang

Thams

et al. 2021

IJMS

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Traumatic brain injury is one of the leading causes of mortality and morbidity in the world with no current pharmacological treatment. The role of BDNF in neural repair and regeneration is well established and has also been the focus of TBI research. Here, we review experimental animal models assessing BDNF expression following injury as well as clinical studies in humans including the role of BDNF polymorphism in TBI. There is a large heterogeneity in experimental setups and hence the results with different regional and temporal changes in BDNF expression. Several studies have also assessed different interventions to affect the BDNF expression following injury. Clinical studies highlight the importance of BDNF polymorphism in the outcome and indicate a protective role of BDNF polymorphism following injury. Considering the possibility of affecting the BDNF pathway with available substances, we discuss future studies using transgenic mice as well as iPSC in order to understand the underlying mechanism of BDNF polymorphism in TBI and develop a possible pharmacological treatment.

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“…39,40 Together, these emerging BDNF biomarker studies demonstrating poorer outcomes with greater BDNF action in the CNS suggest that the apoptotic action of pro-BDNF predominates over the survival signaling of mature BDNF in adults with TBI. The risk conferred by greater BDNF action, however, may be moderated by age, possibly related to reductions in BDNF levels 41 and regional balances of BDNF receptor ratios across the lifespan, 42,43 as has been previously suggested. 17,18 It is interesting that the detrimental effect of higher BDNF action found in adults with TBI contrasts with most evidence in non-brain-injured populations in which lower BDNF action appears to confer risk for psychiatric and neurological conditions.…”

Section: Discussionmentioning

confidence: 79%

Acute Brain-Derived Neurotrophic Factor DNA Methylation Trajectories in Cerebrospinal Fluid and Associations With Outcomes Following Severe Traumatic Brain Injury in Adults

Treble‐Barna

Heinsberg

Puccio

et al. 2021

Neurorehabil Neural Repair

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Background. Epigenetic biomarkers have the potential to explain outcome heterogeneity following traumatic brain injury (TBI) but are largely unexplored. Objective. This exploratory pilot study characterized brain-derived neurotrophic factor ( BDNF) DNA methylation trajectories following severe TBI. Methods. Brain-derived neurotrophic factor DNA methylation trajectories in cerebrospinal fluid (CSF) over the first 5 days following severe TBI in 112 adults were examined in association with 3- and 12-month outcomes. Results. Group-based trajectory analysis revealed low and high DNA methylation groups at two BDNF cytosine-phosphate-guanine (CpG) targets that showed suggestive associations ( P < .05) with outcomes. Membership in the high DNA methylation groups was associated with better outcomes after controlling for age, sex, and injury severity. Associations of age × trajectory group interactions with outcomes at a third CpG site revealed a pattern of the same or better outcomes with higher ages in the high DNA methylation group and worse outcomes with higher ages in the low DNA methylation group. Conclusions. Although no observed associations met the empirical significance threshold after correcting for multiple comparisons, suggestive associations of the main effect models were consistent in their direction of effect and were observed across two CpG sites and two outcome time points. Results suggest that higher acute CSF BDNF DNA methylation may promote recovery following severe TBI in adults, and this effect may be more robust with higher age. While the results require replication in larger and racially diverse independent samples, BDNF DNA methylation may serve as an early postinjury biomarker helping to explain outcome heterogeneity following TBI.

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The Influence of the Val66Met Polymorphism of Brain-Derived Neurotrophic Factor on Neurological Function after Traumatic Brain Injury

Cited by 22 publications

References 113 publications

Brain-derived neurotrophic factor polymorphism Val66Met protects against cancer-related fatigue

Brain-derived neurotrophic factor polymorphism Val66Met protects against cancer-related fatigue

The Role of BDNF in Experimental and Clinical Traumatic Brain Injury

Acute Brain-Derived Neurotrophic Factor DNA Methylation Trajectories in Cerebrospinal Fluid and Associations With Outcomes Following Severe Traumatic Brain Injury in Adults

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