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J Affect Disord. 2010 Oct;126(1-2):223-9. doi: 10.1016/j.jad.2010.03.019. Epub 2010 Apr 15.

Serotonin transporter and BDNF genetic variants interact to predict cognitive reactivity in healthy adults.

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  • 1University of Texas at Austin, TX, USA.



Cognitive theory and empirical evidence both suggest that cognitive reactivity (the tendency to think more negatively when in a sad mood) is an important marker of depression vulnerability. Research has not yet determined whether genetic factors contribute to the expression of cognitive reactivity.


The present study examined associations between the 5-HTTLPR polymorphism of the SLC6A4 gene, the Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene, and cognitive reactivity in a never depressed, unmedicated, young adult sample (N=151).


The interaction between 5-HTTLPR and Val66Met polymorphisms significantly predicted change in dysfunctional thinking from before to after a standardized sad mood provocation. Cognitive reactivity increased among S/L(G) 5-HTTLPR homozygotes if they were also homozygous for the Val Val66Met allele. In contrast, presence of a Met Val66Met allele was associated with attenuated cognitive reactivity among S/L(G) 5-HTTLPR homozygotes.


The sample size of the current study is relatively small for modern genetic association studies. However, results are consistent with previous research demonstrating biological epistasis between SLC6A4 and BDNF for predicting connectivity among neural structures involved in emotion regulation.


The BDNF Met allele may protect S/L(G) 5-HTTLPR homozygotes from increased dysfunctional thinking following a sad mood provocation. Study results are the first to demonstrate an epistatic genetic relationship predicting cognitive reactivity and suggest the need for more complex and integrative models of depression vulnerability.

Copyright 2010 Elsevier B.V. All rights reserved.

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