title: Serotonin transporter and BDNF genetic variants interact to predict cognitive reactivity in healthy adults.
abstract: 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.
authors.affiliation: University of Texas at Austin, TX, USA. wells@mail.utexas.edu
authors.forename: Tony T
authors.initials: TT
authors.lastname: Wells
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Beevers
authors.forename: John E
authors.initials: JE
authors.lastname: McGeary
mesh_terms: 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
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D050486:Serotonin Plasma Membrane Transport Proteins
references.citation: Biol Psychiatry. 2009 Feb 1;65(3):211-9
references.pmid: 18691701
references.citation: Science. 1996 Nov 29;274(5292):1527-31
references.pmid: 8929413
references.citation: J Consult Clin Psychol. 2007 Dec;75(6):1000-5
references.pmid: 18085916
references.citation: Biol Psychol. 2009 Feb;80(2):176-88
references.pmid: 18838100
references.citation: Nat Rev Neurosci. 2006 Oct;7(10):818-27
references.pmid: 16988657
references.citation: Nat Genet. 2001 Nov;29(3):306-9
references.pmid: 11600885
references.citation: Science. 2003 Jul 18;301(5631):386-9
references.pmid: 12869766
references.citation: Biol Psychiatry. 2005 Aug 15;58(4):307-14
references.pmid: 16005437
references.citation: Biol Psychiatry. 2008 May 1;63(9):847-51
references.pmid: 18005940
references.citation: J Affect Disord. 2009 May;115(1-2):215-9
references.pmid: 18842305
references.citation: Neuropsychopharmacology. 2008 Jan;33(1):73-83
references.pmid: 17882234
references.citation: Behav Genet. 1996 Jan;26(1):55-63
references.pmid: 8852732
references.citation: Arch Gen Psychiatry. 2009 Dec;66(12):1287-9
references.pmid: 19996033
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2008 Sep 5;147B(6):814-21
references.pmid: 18205169
references.citation: Biol Psychiatry. 2009 Sep 1;66(5):468-76
references.pmid: 19541292
references.citation: JAMA. 2009 Jun 17;301(23):2462-71
references.pmid: 19531786
references.citation: Nat Neurosci. 2007 Sep;10(9):1089-93
references.pmid: 17726474
references.citation: Emotion. 2009 Aug;9(4):579-84
references.pmid: 19653783
references.citation: Arch Gen Psychiatry. 2006 Jul;63(7):749-55
references.pmid: 16818864
references.citation: J Abnorm Psychol. 2007 Feb;116(1):208-12
references.pmid: 17324031
references.citation: Alcohol Clin Exp Res. 2005 Jan;29(1):8-16
references.pmid: 15654286
references.citation: Nat Neurosci. 2005 Jun;8(6):828-34
references.pmid: 15880108
references.citation: Mol Psychiatry. 2008 Feb;13(2):131-46
references.pmid: 17700575
references.citation: Psychol Assess. 2007 Jun;19(2):199-209
references.pmid: 17563201
references.citation: Psychol Rep. 1974 Jun;34(3):1184-6
references.pmid: 4424377
references.citation: Emotion. 2001 Mar;1(1):25-37
references.pmid: 12894809
references.citation: J Neurochem. 1996 Jun;66(6):2621-4
references.pmid: 8632190
references.citation: Arch Gen Psychiatry. 2004 Dec;61(12):1271-9
references.pmid: 15583118
references.citation: Behav Genet. 1997 May;27(3):251-7
references.pmid: 9210796
references.citation: Pers Individ Dif. 2008;45(5):425-428
references.pmid: 19122845
references.citation: Mol Psychiatry. 2008 Jul;13(7):709-16
references.pmid: 18347599
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2006 Sep 5;141B(6):566-70
references.pmid: 16856124
references.citation: J Abnorm Psychol. 1999 Aug;108(3):483-9
references.pmid: 10466272
references.citation: Psychol Bull. 2004 Jan;130(1):66-79
references.pmid: 14717650
references.citation: Neurosci Lett. 2007 Dec 11;429(1):12-6
references.pmid: 17959306
references.citation: Behav Res Ther. 2004 Sep;42(9):1001-17
references.pmid: 15325898
references.citation: J Abnorm Psychol. 1999 Feb;108(1):3-10
references.pmid: 10066988
references.citation: J Affect Disord. 2008 Apr;107(1-3):227-30
references.pmid: 17804080
references.citation: Proc Biol Sci. 2009 May 22;276(1663):1747-51
references.pmid: 19324793
references.citation: J Affect Disord. 2006 Apr;91(2-3):125-31
references.pmid: 16464506
references.citation: Arch Gen Psychiatry. 2007 Sep;64(9):1096-7
references.pmid: 17768275
references.citation: Behav Res Ther. 2002 Jan;40(1):105-20
references.pmid: 11762423
references.citation: Arch Gen Psychiatry. 1986 Nov;43(11):1076-81
references.pmid: 3767597
references.citation: Genes Brain Behav. 2008 Jul;7(5):543-51
references.pmid: 18266983
references.citation: J Consult Clin Psychol. 2000 Aug;68(4):615-23
references.pmid: 10965637
references.citation: Clin Psychol Rev. 2005 Jun;25(4):487-510
references.pmid: 15914266
references.citation: Psychopharmacology (Berl). 2007 Nov;194(4):545-54
references.pmid: 17628790
references.citation: J Abnorm Psychol. 1990 Aug;99(3):237-41
references.pmid: 2212273
references.citation: J Abnorm Psychol. 2007 Feb;116(1):86-94
references.pmid: 17324019
references.citation: J Abnorm Psychol. 2009 Aug;118(3):670-81
references.pmid: 19685963
references.citation: Am J Hum Genet. 1995 Nov;57(5):1252-4
references.pmid: 7485180
references.citation: Neuropsychopharmacology. 2004 Oct;29(10):1765-81
references.pmid: 15213704
references.citation: Am J Psychiatry. 2008 Aug;165(8):969-77
references.pmid: 18628348
references.citation: Am J Psychiatry. 2003 Jan;160(1):90-9
references.pmid: 12505806
references.citation: Arch Gen Psychiatry. 2005 May;62(5):529-35
references.pmid: 15867106
references.citation: Lancet. 1988 Jun 18;1(8599):1356-8
references.pmid: 2898042