5-HTTLPR/rs25531 polymorphism and neuroticism are linked by resting state functional connectivity of amygdala and fusiform gyrus

Abstract

The s/s-genotype of the 5-HTTLPR polymorphism and the personality trait of neuroticism have both been associated with experiences of negative affect, anxiety and mood disorders, as well as an emotional processing bias towards negative facial emotions. On a neural level, this bias can be characterized by altered amygdala and fusiform gyrus (FFG) activity during perception of negative facial expressions. Using resting-state functional magnetic resonance imaging in a multi-center-sample of 178 healthy subjects of European descent, this study investigated the association of 5-HTTLPR (short s- and long l-allele) including the genotype of the single nucleotide polymorphism (SNP) rs25531 (A/G) within this region polymorphism, and trait neuroticism on resting-state functional connectivity (rs-FC) between amygdala and the FFG. Moreover, we aimed to identify additional brain regions with associations of 5-HTTLPR/rs25531 (combined according to its expression; low: s/s; high: l(A)/l(A); intermediate: s/l(A), s/l(G), l(G)/l(G), l(A)/l(G)) and trait neuroticism to amygdala rs-FC. Separate analyses for 5-HTTLPR/rs25531 and neuroticism (controlling for age, gender, handedness, and research site) revealed that s/s-homozygotes and individuals high in neuroticism obtained altered amygdala rs-FC in the right occipital face area, which is considered to be a "core component" of the face processing system. Importantly, effects of neuroticism were replicated across three independent research sites. Additionally, associations of 5-HTTLPR/rs25531 genotype and amygdala rs-FC were observed in the anterior and posterior cingulate cortex, whereas neuroticism was not related to rs-FC in these areas. The presented data implies that 5-HTTLPR/rs25531 variants and neuroticism are linked by resting state functional connectivity of amygdala and fusiform gyrus and suggests that variants of 5-HTTLPR/rs25531 genotype and different levels of neuroticism may partly account for altered processing of negative facial emotions.

Sex-specific mediation effect of the right fusiform face area volume on the association between variants in repeat length ofAVPR1ARS3 and altruistic behavior in healthy adults

“…We neither found significant between genotypic differences in HA nor significant correlations between the GMV of the right FFA and HA scores. The absence of HA effects on the right FFA seems a bit surprising in light of a recent finding of an association between a personality trait (neuroticism) and the amygdala-FFA functional connectivity [Kruschwitz et al, 2015a]. The discrepancy may be explained by the between-study differences in: (1) imaging metrics: the GMV used in our study is a measure of structural property, whereas, the amygdala-FFA connectivity used in the prior study reflects functional property and is affected by both the amygdala and FFA; (2) personality scales: our study used the HA subscale of the TPQ, but the prior study used neuroticism subscale of NEO; and (3) subregional specificity of the FFA: the coordinate (x 5 39, y 5 252.5, z 5 216.5) of our FFA region is largely different from that (x 5 48, y 5 275, z 5 221) of the prior study.…”

Neuroticism and conscientiousness respectively constrain and facilitate short‐term plasticity within the working memory neural network

“…In healthy individuals, neuroticism, characterized by negative affect, has been associated with disadvantageous changes in cognition, brain structure, anatomical connectivity [Bjørnebekk et al, 2013;DeYoung et al, 2010;Kapogiannis et al, 2013;Kumari et al, 2004;Wright et al, 2006Wright et al, , 2007, and resting state connectivity [Kruschwitz et al, 2015]. Conversely, conscientiousness, characterized by adherence to rules and goals, seems to have a protective role [DeYoung et al, 2010;Forbes et al, 2014;Kapogiannis et al, 2013;Wright et al, 2006Wright et al, , 2007.…”

5‐HTTLPR differentially predicts brain network responses to emotional faces

“…We did not observe significant 5-HTTLPR effects with a univariate approach, which, based on power calculations reported by Murphy et al, [2013], likely partly reflects low statistical power. This is conceptually appealing based on evidence that 5-HTTLPR genotype affects many features of brain function [Firk et al, 2013;Jonassen et al, 2012;Kruschwitz et al, 2014;Stollstorff et al, 2013], not just amygdala reactivity, and that task-condition responses likely reflect multiple interlinked features of brain function. We argue that this multivariate approach is advantageous compared to univariate techniques by modeling shared covariance across brain regions rather than independently modeling variance within voxels or regions.…”

“…We argue that this multivariate approach is advantageous compared to univariate techniques by modeling shared covariance across brain regions rather than independently modeling variance within voxels or regions. This is conceptually appealing based on evidence that 5-HTTLPR genotype affects many features of brain function [Firk et al, 2013;Jonassen et al, 2012;Kruschwitz et al, 2014;Stollstorff et al, 2013], not just amygdala reactivity, and that task-condition responses likely reflect multiple interlinked features of brain function. Conversely, we are unaware of a clear method for partitioning how much of the covariance captured by our latent variable is due to 5-HTTLPR.…”