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


METHODS
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).


RESULTS
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.


CONCLUSIONS
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.


CONCLUSIONS
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.
Wells
Tony T
TT
University of Texas at Austin, TX, USA. wells@mail.utexas.edu
Beevers
Christopher G
CG
McGeary
John E
JE
D000339:Affect; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000502:physiology; D003071:Cognition; D003863:Depression / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011569:Psychiatric Status Rating Scales; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics* / Q000502:physiology; D055815:Young Adult
D019208:Brain-Derived Neurotrophic Factor; D050486:Serotonin Plasma Membrane Transport Proteins
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