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Depressive Emotionality Moderates the Influence of the BDNF Val66Met Polymorphism on Executive Functions and on Unconscious Semantic Priming.

ABSTRACT: 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.

SUBMITTER: Sanwald S

PROVIDER: S-EPMC7152588 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Depressive Emotionality Moderates the Influence of the BDNF Val66Met Polymorphism on Executive Functions and on Unconscious Semantic Priming.

Sanwald Simon S Montag Christian C Kiefer Markus M

Journal of molecular neuroscience : MN 20200130 5

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 Val66 ...[more]

PMID: 32002751

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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: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.

Dataset Information

Depressive Emotionality Moderates the Influence of the BDNF Val66Met Polymorphism on Executive Functions and on Unconscious Semantic Priming.

Publications

Depressive Emotionality Moderates the Influence of the BDNF Val66Met Polymorphism on Executive Functions and on Unconscious Semantic Priming.

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