The BDNF Val66Met polymorphism does not moderate the effect of self-reported physical activity on depressive symptoms in midlife

Gujral, Swathi; Manuck, Stephen B.; Ferrell, Robert E.; Flory, Janine D.; Erickson, Kirk I.

doi:10.1016/j.psychres.2014.03.028

Cited by 22 publications

(24 citation statements)

References 59 publications

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“…Interestingly, this interaction between PA and the BDNF gene has not emerged with respect to depression outcomes. Despite one study in adolescent girls showing that PA was associated with fewer depressive symptoms for Met carriers (Mata et al 2010), more recent larger-scale studies (N >1,000) of depressive symptoms in both adolescents and adults have failed to replicate this effect (Gujral et al 2014, Stavrakakis et al 2013. These results suggest that the interaction between BDNF (or other genes) and PA may depend on the phenotype of interest, with cognitive outcomes showing different patterns than mood outcomes.…”

Section: Interactions Between Physical Activity and Gene Polymorphismsmentioning

confidence: 86%

Physical Activity and Cognitive Vitality

Prakash

Voss

Erickson

et al. 2015

Annu. Rev. Psychol.

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277

228

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We examine evidence supporting the associations among physical activity (PA), cognitive vitality, neural functioning, and the moderation of these associations by genetic factors. Prospective epidemiological studies provide evidence for PA to be associated with a modest reduction in relative risk of cognitive decline. An evaluation of the PA-cognition link across the life span provides modest support for the effect of PA on preserving and even enhancing cognitive vitality and the associated neural circuitry in older adults, with the majority of benefits seen for tasks that are supported by the prefrontal cortex and the hippocampus. The literature on children and young adults, however, is in need of well-powered randomized controlled trials. Future directions include a more sophisticated understanding of the dose-response relationship, the integration of genetic and epigenetic approaches, inclusion of multimodal imaging of brain-behavior changes, and finally the design of multimodal interventions that may yield broader improvements in cognitive function.

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Section: Interactions Between Physical Activity and Gene Polymorphismsmentioning

confidence: 86%

Physical Activity and Cognitive Vitality

Prakash

Voss

Erickson

et al. 2015

Annu. Rev. Psychol.

Self Cite

277

228

View full text Add to dashboard Cite

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“…However, the behavioral benefits vary in different subjects, suggesting that different factors may interact to produce distinct consequences. Indeed, some studies have addressed whether the BDNF Val66Met polymorphism moderates the response to exercise in human, producing mixed and inconclusive results, probably depending on the ethnic group, gender, age, and type and frequency of the exercise considered (Brown et al, 2014;Gujral et al, 2014;Hopkins et al, 2012;Lemos et al, 2016;Mata et al, 2010;Nascimento et al, 2015).…”

Section: Physical Exercise-induced Reduction Of Body Weight Gainmentioning

confidence: 99%

“…Val66Met SNP is associated with increased susceptibility to cognitive deficits and neuropsychiatric disorders Hariri et al, 2003;Lim et al, 2014;Notaras et al, 2015;Verhagen et al, 2010). Despite the strong evidence that exercise increases BDNF expression, only a few human studies have been conducted to address the potential role of Val66Met SNP in moderating exercise response, showing inconclusive results, probably due to confounding factors (Brown et al, 2014;Gujral et al, 2014;Hopkins et al, 2012;Lemos et al, 2016;Mata et al, 2010;Nascimento et al, 2015). Animal models may offer a useful tool to better address such question in a well-controlled environment and genetic setting.…”

Section: Introductionmentioning

confidence: 99%

Brain-Derived Neurotrophic Factor Val66Met Human Polymorphism Impairs the Beneficial Exercise-Induced Neurobiological Changes in Mice

Ieraci

Madaio

Mallei

et al. 2016

Neuropsychopharmacol

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Several studies have shown that exercise improves cognitive functions and emotional behaviors. Positive effects of exercise have been associated with enhanced brain plasticity, adult hippocampal neurogenesis, and increased levels of brain-derived neurotrophic factor (BDNF). However, a substantial variability of individual response to exercise has been described, which may be accounted for by individual genetic variants. Here, we have assessed whether and how the common human BDNF Val66Met polymorphism influences the neurobiological effects modulated by exercise in BDNF Val66Met knock-in male mice. Wild-type (BDNF Val/Val ) and homozygous BDNF Val66Met (BDNF Met/Met ) male mice were housed in cages equipped with or without running wheels for 4 weeks. Changes in behavioral phenotype, hippocampal adult neurogenesis, and gene expression were evaluated in exercised and sedentary control mice. We found that exercise reduced the latency to feed in the novelty suppressed feeding and the immobility time in the forced swimming test in BDNF Met/Met mice had lower basal BDNF protein levels in the hippocampus, which was not recovered following exercise. Moreover, exercise-induced expression of total BDNF, BDNF splice variants 1, 2, 4, 6 and fibronectin type III domain-containing protein 5 (FNDC5) mRNA levels were absent or reduced in the dentate gyrus of BDNF Met/Met mice. Exercise failed to enhance PGC-1α and FNDC5 mRNA levels in the BDNF Met/Met muscle. Overall these results indicate that, in adult male mice, the BDNF Val66Met polymorphism impairs the beneficial behavioral and neuroplasticity effects induced by physical exercise.

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“…One study reported that young adults with at least one 5-HTT L allele showed greater reductions in depressive symptoms after a 5-week exercise intervention [10]. In contrast, a recent cross-sectional study in middle-aged adults found that the BDNF Val66Met polymorphism did not moderate the relationship between self-reported physical activity and depressive symptoms [11]. This question has not been investigated in older adults.…”

Section: Introductionmentioning

confidence: 99%

“…Numerous studies have shown that men and women not only differ in their risk for depression and vulnerability to depression-related negative sequelae, but also in the associations of genotype with depression risk and response to depression treatment [16, 17]. Some studies have reported a sex difference on the relationship between PA and depressive symptoms, with the effect being found exclusively or to a greater extent in either men [e.g., 18] or women [e.g., 11]. A recent meta-analysis of randomized trials showed a stronger effect of exercise in men [19].…”

Section: Introductionmentioning

confidence: 99%

Genetic Moderators of the Impact of Physical Activity on Depressive Symptoms

Dotson¹,

Hsu²,

Langaee³

et al. 2016

J Frailty Aging

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Background: Converging evidence suggests that physical activity is an effective intervention for both clinical depression and sub-threshold depressive symptoms; however, findings are not always consistent. These mixed results might reflect heterogeneity in response to physical activity, with some subgroups of individuals responding positively, but not others. Objectives: 1) To examine the impact of genetic variation and sex on changes in depressive symptoms in older adults after a physical activity (PA) intervention, and 2) to determine if PA differentially improves particular symptom dimensions of depression. Design: Randomized controlled trial. Setting: Four field centers (Cooper Institute, Stanford University, University of Pittsburgh, and Wake Forest University). Participants: 396 community-dwelling adults aged 70–89 years who participated in the Lifestyle Interventions and Independence for Elders Pilot Study (LIFE-P). Intervention: 12-month PA intervention compared to an education control. Measurements: Polymorphisms in the serotonin transporter (5-HTT), brain-derived neurotrophic factor (BDNF), and apolipoprotein E (APOE) genes; 12-month change in the Center for Epidemiologic Studies Depression Scale total score, as well as scores on the depressed affect, somatic symptoms, and lack of positive affect subscales. Results: Men randomized to the PA arm showed the greatest decreases in somatic symptoms, with a preferential benefit in male carriers of the BDNF Met allele. Symptoms of lack of positive affect decreased more in men compared to women, particularly in those possessing the 5-HTT L allele, but the effect did not differ by intervention arm. APOE status did not affect change in depressive symptoms. Conclusions: Results of this study suggest that the impact of PA on depressive symptoms varies by genotype and sex, and that PA may mitigate somatic symptoms of depression more than other symptoms. The results suggest that a targeted approach to recommending PA therapy for treatment of depression is viable.

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The BDNF Val66Met polymorphism does not moderate the effect of self-reported physical activity on depressive symptoms in midlife

Cited by 22 publications

References 59 publications

Physical Activity and Cognitive Vitality

Physical Activity and Cognitive Vitality

Brain-Derived Neurotrophic Factor Val66Met Human Polymorphism Impairs the Beneficial Exercise-Induced Neurobiological Changes in Mice

Genetic Moderators of the Impact of Physical Activity on Depressive Symptoms

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