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Impact of BDNF Val66Met and 5-HTTLPR polymorphism variants on neural substrates related to sadness and executive function.

Publication ,  Journal Article
Wang, L; Ashley-Koch, A; Steffens, DC; Krishnan, KRR; Taylor, WD
Published in: Genes Brain Behav
April 2012

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.

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Published In

Genes Brain Behav

DOI

EISSN

1601-183X

Publication Date

April 2012

Volume

11

Issue

3

Start / End Page

352 / 359

Location

England

Related Subject Headings

  • Valine
  • Serotonin Plasma Membrane Transport Proteins
  • Polymorphism, Genetic
  • Neurons
  • Neurology & Neurosurgery
  • Middle Aged
  • Methionine
  • Male
  • Humans
  • Genotype
 

Citation

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Wang, L., Ashley-Koch, A., Steffens, D. C., Krishnan, K. R. R., & Taylor, W. D. (2012). Impact of BDNF Val66Met and 5-HTTLPR polymorphism variants on neural substrates related to sadness and executive function. Genes Brain Behav, 11(3), 352–359. https://doi.org/10.1111/j.1601-183X.2012.00764.x
Wang, L., A. Ashley-Koch, D. C. Steffens, K. R. R. Krishnan, and W. D. Taylor. “Impact of BDNF Val66Met and 5-HTTLPR polymorphism variants on neural substrates related to sadness and executive function.Genes Brain Behav 11, no. 3 (April 2012): 352–59. https://doi.org/10.1111/j.1601-183X.2012.00764.x.
Wang L, Ashley-Koch A, Steffens DC, Krishnan KRR, Taylor WD. Impact of BDNF Val66Met and 5-HTTLPR polymorphism variants on neural substrates related to sadness and executive function. Genes Brain Behav. 2012 Apr;11(3):352–9.
Wang, L., et al. “Impact of BDNF Val66Met and 5-HTTLPR polymorphism variants on neural substrates related to sadness and executive function.Genes Brain Behav, vol. 11, no. 3, Apr. 2012, pp. 352–59. Pubmed, doi:10.1111/j.1601-183X.2012.00764.x.
Wang L, Ashley-Koch A, Steffens DC, Krishnan KRR, Taylor WD. Impact of BDNF Val66Met and 5-HTTLPR polymorphism variants on neural substrates related to sadness and executive function. Genes Brain Behav. 2012 Apr;11(3):352–359.
Journal cover image

Published In

Genes Brain Behav

DOI

EISSN

1601-183X

Publication Date

April 2012

Volume

11

Issue

3

Start / End Page

352 / 359

Location

England

Related Subject Headings

  • Valine
  • Serotonin Plasma Membrane Transport Proteins
  • Polymorphism, Genetic
  • Neurons
  • Neurology & Neurosurgery
  • Middle Aged
  • Methionine
  • Male
  • Humans
  • Genotype