The BDNF Val66Met polymorphism moderates the relationship between cognitive reserve and executive function.
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ABSTRACT:
SUBMITTER: Ward DD
PROVIDER: S-EPMC4490292 | biostudies-other | 2015
REPOSITORIES: biostudies-other
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Project description:INTRODUCTION:Cognitive reserve (CR) and BDNF Val66Met are independently associated with the rate of cognitive decline in preclinical Alzheimer's disease. This study was designed to investigate the interactive effects of these variables on 36-month cognitive change in cognitively intact older adults. METHODS:Data for this investigation were obtained from 445 community-residing participants of the Tasmanian Healthy Brain Project, who underwent genetic screening and annual assessment of neuropsychological, health, and psychosocial function. RESULTS:Our main result was that BDNF Val66Met moderated the relationship between baseline CR and change in executive function performance, in that CR-related differences in function decreased across the follow-up period in BDNF Val homozygotes, but became more pronounced in BDNF Met carriers. Similar effects were not observed within the other memory- and language-related cognitive domains. DISCUSSION:Inheritance of BDNF Met may be associated with a detrimental influence on the relationship between CR and cognitive change in cognitively intact older adults, but this effect may be restricted to the executive function domain.
| S-EPMC5651414 | biostudies-literature
Project description:Automatic semantic processing can be assessed using semantic priming paradigms. Individual differences in semantic priming have been associated with differences in executive functions. The brain-derived neurotrophic factor (BDNF) Val66Met (substitution of valine (Val) to methionine (Met) at codon 66) polymorphism has been shown to be associated with executive functions as well as depression. Depression-associated variables such as depressed mood also moderated the relationship between BDNF Val66Met and executive functions in previous work. In this study, we therefore aimed at investigating whether BDNF Val66Met genotype modulates masked and unmasked semantic priming as well as executive functions and whether sadness is a moderator of these associations. We collected data of N?=?155 participants measuring reaction times (RTs) as well as error rates (ERs) in masked and unmasked semantic priming paradigms using a lexical decision task. We assessed the primary emotion of SADNESS using the Affective Neuroscience Personality Scale (ANPS) and working memory using digit span forward and backward tasks. Met+ carriers showed reduced RT priming and increased ER priming in the masked priming paradigm. Even though there was no direct association between BDNF Val66Met and executive functions, SADNESS significantly moderated the association between BDNF Val66Met and executive functions as well as masked RT priming. We suggest that Met+ individuals with low depressive tendencies have not only superior EF, but also a faster and more superficial processing style, compared with Val/Val homozygotes. However, in Met+ individuals, cognitive functioning exhibits a greater vulnerability to depressed emotionality compared with Val/Val homozygotes. Our study thus demonstrates how emotional and molecular genetic factors exert an interacting influence on higher-level cognition.
| S-EPMC7152588 | biostudies-literature
Project description:The brain-derived neurotrophic factor (BDNF) Val(66) Met allelic variation is linked to both the occurrence of mood disorders and antidepressant response. These findings are not universally observed, and the mechanism by which this variation results in increased risk for mood disorders is unclear. One possible explanation is an epistatic relationship with other neurotransmitter genes associated with depression risk, such as the serotonin-transporter-linked promotor region (5-HTTLPR). Further, it is unclear how the coexistence of the BDNF Met and 5-HTTLPR S variants affects the function of the affective and cognitive control systems. To address this question, we conducted a functional magnetic resonance imaging (fMRI) study in 38 older adults (20 healthy and 18 remitted from major depressive disorder). Subjects performed an emotional oddball task during the fMRI scan and provided blood samples for genotyping. Our analyses examined the relationship between genotypes and brain activation to sad distractors and attentional targets. We found that 5-HTTLPR S allele carriers exhibited stronger activation in the amygdala in response to sad distractors, whereas BDNF Met carriers exhibited increased activation to sad stimuli but decreased activation to attentional targets in the dorsolateral prefrontal and dorsomedial prefrontal cortices. In addition, subjects with both the S allele and Met allele genes exhibited increased activation to sad stimuli in the subgenual cingulate and posterior cingulate. Our results indicate that the Met allele alone or in combination with 5-HTTLPR S allele may increase reactivity to sad stimuli, which might represent a neural mechanism underlying increased depression vulnerability.
| S-EPMC3654542 | biostudies-other
Project description:There is extensive variability in cocaine-related attentional bias (AB) following trauma script exposure among cocaine-dependent (CD) patients with posttraumatic stress disorder (PTSD). Therefore, research is needed to identify the specific PTSD-CD patients most likely to exhibit an AB to cocaine cues. A common polymorphism in brain-derived neurotrophic factor (BDNF), Val66met, is associated with risk for stimulant addiction, and thus, was examined as a moderator of the association between PTSD and cocaine-related AB following trauma script exposure in this study. Adult CD patients with (n = 17) and without (n = 28) PTSD were exposed to a personalized trauma script, followed by a visual dot-probe task assessing cocaine-related AB. Task response times were used to examine traditionally calculated AB scores, as well as trial level bias scores (TL-BS) that more accurately model the temporal dynamics of AB. PTSD-CD patients homozygous for the BDNF Val/Val genotype exhibited greater bias for attending to cocaine-related stimuli following trauma script exposure than those carrying the Met allele. The PTSD by BDNF interaction did not predict response time variability on trials for which only neutral stimuli were presented, thus increasing confidence that the observed effect is specific to cocaine-related stimuli. PTSD-CD patients homozygous for the BDNF Val/Val genotype may be at particularly high risk for negative clinical outcomes (e.g., relapse, treatment dropout) as a function of prolonged attentional engagement with cocaine cues when exposed to trauma reminders.
| S-EPMC7314419 | biostudies-literature
Project description:The val(66)met polymorphism in brain-derived neurotrophic factor (BDNF) has been associated with poorer outcomes after stroke. The mechanism for this finding remains uncertain but might be related to the reduced motor system activation associated with this polymorphism in healthy people.The current study examined whether the presence of the BDNF val(66)met polymorphism is associated with reduced motor system activation after stroke.Forty-two patients with stroke who were enrolled in 1 of 2 studies of robot-assisted arm motor therapy participated in the study. All participants were tested for the BDNF val(66)met polymorphism followed by functional magnetic resonance imaging during affected hand movement.Participants averaged 12 months poststroke and had wide-ranging motor deficits (Fugl-Meyer scale scores=14-60). Brain activation in participants without the BDNF val(66)met polymorphism (n=26) spanned bilateral motor networks with a larger volume (total=334 cc) than that found in participants with this polymorphism (n=16) (97 cc). Regional analyses were consistent. Participants without this polymorphism showed larger ipsilesional primary sensorimotor cortex activation volume and magnitude compared with those in whom the polymorphism was present.The extent to which these findings generalize to other populations of people with stroke, such as those with stroke <7 days prior, remains uncertain.Functional magnetic resonance imaging during affected hand movement showed decreased brain activation among participants with the BDNF val(66)met polymorphism compared with those lacking this polymorphism, especially in the ipsilesional primary sensorimotor cortex contralateral to movement. These results echo findings in healthy people and suggest that genetic factors affecting the normal brain continue to be operative after stroke. The findings suggest a potential imaging-based endophenotype for the BDNF val(66)met polymorphism's effect on the motor system that may be useful in a clinical trial setting.
| S-EPMC4817211 | biostudies-other
Project description:We explored the effect of the Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism (rs6265) on correlation between changes in plasma BDNF levels with cognitive function and quality of life (QoL) after 12 weeks of treatment in bipolar disorder (BD). Symptom severity and plasma BDNF levels were assessed upon recruitment and during weeks 1, 2, 4, 8 and 12. QoL, the Wisconsin Card Sorting Test (WCST), and the Conners' Continuous Performance Test (CPT) were assessed at baseline and endpoint. The BDNF Val66Met polymorphism was genotyped. Changes in cognitive function and QoL over 12 weeks were reduced using factor analysis for the evaluation of their correlations with changes in plasma BDNF. Five hundred forty-one BD patients were recruited and 65.6% of them completed the 12-week follow-up. Changes in plasma BDNF levels with factor 1 (WCST) were significantly negatively correlated (r?=?-0.25, p?=?0.00037). After stratification of BD subtypes and BDNF genotypes, this correlation was significant only in BP-I and the Val/Met genotype (r?=?-0.54, p?=?0.008). We concluded that changes in plasma BDNF levels significantly correlated with changes in WCST scores in BD and is moderated by the BDNF Val66Met polymorphism and the subtype of BD.
| S-EPMC5131343 | biostudies-literature
Project description:OBJECTIVE:Both clinical and biological factors influence the course of depressive disorders. This study tested for associations between the brain-derived neurotrophic factor (BDNF) gene at the Val66Met locus and the course of major depressive disorder (MDD). METHODS:Three hundred ten Korean subjects (209 patients, 101 controls) were genotyped for rs6265 at nucleotide 196 (G/A), which produces an amino acid substitution at codon 66 (Val66Met) of the gene for BDNF. Course of illness was evaluated both by chronicity of current episode (episode duration >24 months) and by the lifetime history of recurrences. RESULTS:Patients with the Met/Met BDNF genotype had a significantly higher rate of chronic depression than all others. There was a significant dose effect of the Met allele on chronicity. Compared with the Val/Val genotype, the relative risk of chronicity was 1.67 for the Val/Met genotype, and 2.58 for the Met/Met genotype. Lifetime history of recurrent episodes was not related to BDNF genotypes but was significantly associated with younger age of onset and with a history of depression in first degree relatives. CONCLUSION:BDNF genotyping may be informative for anticipating chronicity in major depression.
| S-EPMC3590431 | biostudies-literature
Project description:BackgroundAerobic exercise promotes cognitive function in older adults; however, variability exists in the degree of benefit. The brain-derived neurotropic factor (BDNF) Val66Met polymorphism and biological sex are biological factors that have been proposed as important modifiers of exercise efficacy. Therefore, we assessed whether the effect of aerobic exercise on executive functions was dependent on the BDNFval66met genotype and biological sex.MethodsWe used data from a single-blind randomized controlled trial in older adults with subcortical ischemic vascular cognitive impairment (NCT01027858). Fifty-eight older adults were randomly assigned to either the 6 months, three times per week progressive aerobic training (AT) group or the usual care plus education control (CON) group. The secondary aim of the parent study included executive functions which were assessed with the Trail Making Test (B-A) and the Digit Symbol Substitution Test at baseline and trial completion at 6 months.ResultsAnalysis of covariance, controlling for baseline global cognition and baseline executive functions performance (Trail Making Test or Digit Symbol Substitution Test), tested the three-way interaction between experimental group (AT, CON), BDNFval66met genotype (Val/Val carrier, Met carrier), and biological sex (female, male). Significant three-way interactions were found for the Trail Making Test (F(1,48) = 4.412, p < 0.04) and Digit Symbol Substitution Test (F(1,47) = 10.833, p < 0.002). Posthoc analyses showed female Val/Val carriers benefited the most from 6 months of AT compared with CON for Trail Making Test and Digit Symbol Substitution Test performance. Compared with CON, AT did not improve Trail Making Test performance in male Val/Val carriers or Digit Symbol Substitution Test performance in female Met carriers.ConclusionsThese results suggest that future randomized controlled trials should take into consideration BDNF genotype and biological sex to better understand the beneficial effects of AT on cognitive function in vascular cognitive impairment to maximize the beneficial effects of exercise and help establish exercise as medicine for cognitive health.
| S-EPMC10069071 | biostudies-literature
Project description:SEE ROGAEVA AND SCHMITT-ULMS DOI101093/AWW201 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is implicated in synaptic excitation and neuronal integrity, and has previously been shown to moderate amyloid-β-related memory decline and hippocampal atrophy in preclinical sporadic Alzheimer's disease. However, the effect of BDNF in autosomal dominant Alzheimer's disease is unknown. We aimed to determine the effect of BDNF Val66Met on cognitive function, hippocampal function, tau and amyloid-β in preclinical autosomal dominant Alzheimer's disease. We explored effects of apolipoprotein E (APOE) ε4 on these relationships. The Dominantly Inherited Alzheimer Network conducted clinical, neuropsychological, genetic, biomarker and neuroimaging measures at baseline in 131 mutation non-carriers and 143 preclinical autosomal dominant Alzheimer's disease mutation carriers on average 12 years before clinical symptom onset. BDNF genotype data were obtained for mutation carriers (95 Val66 homozygotes, 48 Met66 carriers). Among preclinical mutation carriers, Met66 carriers had worse memory performance, lower hippocampal glucose metabolism and increased levels of cerebrospinal fluid tau and phosphorylated tau (p-tau) than Val66 homozygotes. Cortical amyloid-β and cerebrospinal fluid amyloid-β42 levels were significantly different from non-carriers but did not differ between preclinical mutation carrier Val66 homozygotes and Met66 carriers. There was an effect of APOE on amyloid-β levels, but not cognitive function, glucose metabolism or tau. As in sporadic Alzheimer's disease, the deleterious effects of amyloid-β on memory, hippocampal function, and tau in preclinical autosomal dominant Alzheimer's disease mutation carriers are greater in Met66 carriers. To date, this is the only genetic factor found to moderate downstream effects of amyloid-β in autosomal dominant Alzheimer's disease.
| S-EPMC5815565 | biostudies-literature
Project description:Nicotine use is associated with the upregulation of brain-derived neurotrophic factor (BDNF) in serum. An association between smoking and the BDNF Val(66)Met polymorphism has also been found. The aim of this study is to examine the levels of serum BDNF in never-smokers, former smokers, and current smokers-with and without nicotine dependence-and to examine the interaction of the polymorphism and smoking status with serum BDNF.We used baseline serum and gene data of BDNF on 2,088 participants from the Netherlands Study of Depression and Anxiety (NESDA) to investigate smoking-BDNF association while controlling for potential confounding variables. Nicotine dependence was assessed with the Fagerstrom Test for Nicotine Dependence (FTND).Smokers with and without nicotine dependence had higher levels of serum BDNF than former and never-smokers. Nicotine dependence and number of cigarettes smoked per day did not add to the prediction of serum BDNF; however, total number of smoking years was a significant predictor of serum BDNF. There was no association of BDNF Val(66)Met, nor an interaction of this polymorphism and smoking status, with serum BDNF.Current smoking and higher number of smoking years are associated with higher levels of serum BDNF, and this is independent of the BDNF genotype. Nicotine dependence itself is not associated with a further increase or decrease of serum BDNF. Longitudinal investigations that address changes in serum BDNF in incident smokers and/or in quitters may be useful to understand the association of smoking with BDNF.
| S-EPMC4837993 | biostudies-literature