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/LG 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/LG 5-HTTLPR homozygotes. Limitations 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/LG 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.

Serotonin transporter andBDNFpolymorphisms interact to predict trait worry

“…Whereas other studies have consistently linked 5-HTTLPR genotypes with trait anxiety (see Schinka et al, 2004), our results demonstrate the importance of also considering BDNF genotypes when examining the tendency to worry. These findings are consistent with previous evidence of an epistatic relationship between 5-HTTLPR and BDNF genotypes at the neural level (e.g., connectivity and interactions between amygdala and anterior cingulate; see Pezawas et al, 2008 and Outhred et al, 2012), as well as predicting other traits associated with emotional distress (e.g., stress-induced rumination, Clasen et al, 2011; cognitive reactivity, Wells et al, 2010). More generally, the results from this study provide preliminary evidence about the putative genetic etiology of trait worry, and illustrate the potential utility of examining transdiagnostic phenotypes and gene-by-gene interactions in genetic research.…”

“…A total of 173 individuals (68% female; mean age = 25.3, SD = 9.7, range = 17–69) participated in the study (note: this sample is independent from those used by Wells et al, 2010 and Clasen et al, 2011). These individuals were recruited from the Austin community via introductory psychology classes at the University of Texas and advertisements placed online, on campus, and at various locations around the city (e.g., community centers, libraries, coffee shops).…”

Toward an integration of cognitive and genetic models of risk for depression

“…Depression often follows the onset of life stress (Kessler, 1997), so how an individual processes emotional information in the context of a negative mood may be particularly important for revealing a cognitive vulnerability to depression (Scher, Ingram, & Segal, 2005). Consistent with this approach, the interaction between 5-HTTLPR and BDNF Val66Met polymorphisms significantly predicted change in dysfunctional thinking from before to after a sad mood induction (Wells, Beevers, & McGeary, 2010). Specifically, carriers of two copies of the lower expressing 5-HTTLPR alleles (S or L G ) who were also homozygous for the BDNF Val allele endorsed higher levels of dysfunctional attitudes after a dysphoric mood induction.…”

Appraisals of Stressful Life Events as a Genetically-Linked Mechanism in the Stress–Depression Relationship

“…First, although the genetic architecture of stress appraisals is purported to be simpler than that of syndromal depression, multiple genes almost certainly co-participate in causing individual differences in stress reactivity (e.g., Conway et al 2010;Jabbi et al 2007;Wells et al 2010). Future studies with sufficiently large samples should examine potential gene-gene interactions involving 5-HTTLPR in predicting stress sensitivity outcomes.…”