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BDNF Val66Met Polymorphism as a Moderator of Exercise Enhancement of Smoking Cessation Treatment in Anxiety Vulnerable Adults.

ABSTRACT: BACKGROUND:Exercise interventions facilitate odds of quit success among high-anxiety sensitive adults smokers. We examined the dependency of these benefits on the genetic BDNF Val66Met (rs6265) polymorphism; individuals who are Met carriers have lower BDNF responses and reduced associated benefits from exercise. Accordingly, we hypothesized that the efficacy of vigorous exercise for smoking cessation would be specific to high-anxiety sensitive Val/Val carriers. METHODS:Participants were adults (N=55) of European ancestry who had participated in a randomized controlled trial comparing a smoking cessation program augmented with exercise vs. augmented with a wellness control treatment. In this secondary analysis, growth curve models for point-prevalence abstinence (PPA) and prolonged abstinence (PA) employed for the main outcome analyses were amended to test the moderator effects of the BDNF Val66Met polymorphism. RESULTS:Consistent with prediction, the advantage of exercise over control for PPA was significantly greater among high-anxiety sensitive persons with the Val/Val genotype than for those with the Val/Met genotype. This advantage did not reach statistical significance for PA. Differences in abstinence between the exercise and control interventions among low-anxiety sensitive smokers were not dependent on the BDNF Val66Met polymorphism. CONCLUSIONS:We found that the efficacy of exercise for augmenting smoking cessation treatment is intensified among high-anxiety sensitive smokers who are Val/Val carriers. This observation is consistent with findings documenting BDNF mediation of exercise benefits and greater negative affect among smokers who are Val/Val carriers. These data encourage further evaluation of the association between the BDNF polymorphism, exercise, anxiety sensitivity, and smoking cessation.

SUBMITTER: Smits JA

PROVIDER: S-EPMC4955634 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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BDNF Val66Met Polymorphism as a Moderator of Exercise Enhancement of Smoking Cessation Treatment in Anxiety Vulnerable Adults.

Smits Jasper A J JA Powers Mark B MB Rosenfield David D Zvolensky Michael J MJ Jacquart Jolene J Davis Michelle L ML Beevers Christopher G CG Marcus Bess H BH Church Timothy S TS Otto Michael W MW

Mental health and physical activity 20160301

<h4>Background</h4>Exercise interventions facilitate odds of quit success among high-anxiety sensitive adults smokers. We examined the dependency of these benefits on the genetic BDNF Val66Met (rs6265) polymorphism; individuals who are Met carriers have lower BDNF responses and reduced associated benefits from exercise. Accordingly, we hypothesized that the efficacy of vigorous exercise for smoking cessation would be specific to high-anxiety sensitive Val/Val carriers.<h4>Methods</h4>Participant ...[more]

PMID: 27453731

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Project description:BackgroundBrain-derived neurotrophic factor (BDNF) is a candidate for susceptibility locus of Panic disorder (PD). However, the findings about the role of the BDNF Val66Met variant in PD were not consistent. Till now, the relationship between BDNF Val66Met polymorphism and anxiety-related traits in PD patients has been rarely explored. This study aimed to explore the relationship among BDNF Val66Met polymorphism, plasma BDNF level and anxiety-related trait in Chinese PD patients.MethodThis multi-center study included 116 PD patients and 99 health controls. We detected single-nucleotide polymorphism (SNP) of BDNF rs6265 (Val66Met) and BDNF plasma level in the two groups. In addition, PD patients were administered the State-Trait Anxiety Inventory (STAI), Panic Disorder Severity Scale-Chinese Version (PDSS-CV) and Hamilton Anxiety Rating Scale (HAMA-14). Quantitative comparison of the differences of BDNF concentration among subjects with different genotypes and association between BDNF Val66Met genotype and trait anxiety were performed.ResultsThere were no significant differences in the genotype frequency (p = 0.79) or allele frequency (p = 0.88) between PD patients and health controls. BDNF plasma levels of PD patients were significantly lower than those in control group (p = 0.003). BDNF plasma levels of the Met/Met genotype were significantly lower than those of Val/Met genotype in PD patients (p = 0.033). PD patients carried Met/Met genotype showed significantly higher scores in STAI trait compared to those carried Val/Val genotype (p = 0.045) and Val/Met genotype (p = 0.018). STAI trait scores of PD patients with agoraphobia were significantly higher than those of patients without agoraphobia (p < 0.05). The ANCOVA showed that the dependent variable STAI trait score was significantly affected by factor "genotype" (Val/Val, Val/Met, Met/Met, p = 0.029), and covariate "agoraphobia" (p = 0.008). In this model, 11.5% of the variance of the STAI trait score was explained by the BDNF genotype. Contrast analysis showed STAI trait scores of Met/Met subjects were significantly higher than those of Val/Met (p = 0.018) and Val/Val individuals (p = 0.045).ConclusionWe found that anxiety trait was associated with the BDNF polymorphism in PD patients. BDNF Met/Met genotype may decrease plasma BDNF level and increase trait anxiety in panic disorder.

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.

Project description:Brain-derived neurotrophic factor (BDNF) has been directly related to exercise-enhanced motor performance in the neurologically injured animal model; however literature concerning the role of BDNF in the enhancement of motor learning in the human population is limited. Previous studies in healthy subjects have examined the relationship between intensity of an acute bout of exercise, increases in peripheral BDNF and motor learning of a simple isometric upper extremity task. The current study examined the role of high intensity exercise on upregulation of peripheral BDNF levels as well as the role of high intensity exercise in mediation of motor learning and retention of a novel locomotor task in neurologically intact adults. In addition, the impact of a single nucleotide polymorphism in the BDNF gene (Val66Met) in moderating the relationship between exercise and motor learning was explored. It was hypothesized that participation in high intensity exercise prior to practicing a novel walking task (split-belt treadmill walking) would elicit increases in peripheral BDNF as well as promote an increased rate and magnitude of within session learning and retention on a second day of exposure to the walking task. Within session learning and retention would be moderated by the presence or absence of Val66Met polymorphism. Fifty-four neurologically intact participants participated in two sessions of split-belt treadmill walking. Step length and limb phase were measured to assess learning of spatial and temporal parameters of walking. Serum BDNF was collected prior to and immediately following either high intensity exercise or 5min of quiet rest. The results demonstrated that high intensity exercise provides limited additional benefit to learning of a novel locomotor pattern in neurologically intact adults, despite increases in circulating BDNF. In addition, presence of a single nucleotide polymorphism on the BDNF gene did not moderate the magnitude of serum BDNF increases with high intensity exercise, nor did it moderate the relationship between high intensity exercise and locomotor learning.

Dataset Information

BDNF Val66Met Polymorphism as a Moderator of Exercise Enhancement of Smoking Cessation Treatment in Anxiety Vulnerable Adults.

Publications

BDNF Val66Met Polymorphism as a Moderator of Exercise Enhancement of Smoking Cessation Treatment in Anxiety Vulnerable Adults.

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