5‐HTTLPR differentially predicts brain network responses to emotional faces

Abstract

The effects of the 5-HTTLPR polymorphism on neural responses to emotionally salient faces have been studied extensively, focusing on amygdala reactivity and amygdala-prefrontal interactions. Despite compelling evidence that emotional face paradigms engage a distributed network of brain regions involved in emotion, cognitive and visual processing, less is known about 5-HTTLPR effects on broader network responses. To address this, we evaluated 5-HTTLPR differences in the whole-brain response to an emotional faces paradigm including neutral, angry and fearful faces using functional magnetic resonance imaging in 76 healthy adults. We observed robust increased response to emotional faces in the amygdala, hippocampus, caudate, fusiform gyrus, superior temporal sulcus and lateral prefrontal and occipito-parietal cortices. We observed dissociation between 5-HTTLPR groups such that LA LA individuals had increased response to only angry faces, relative to neutral ones, but S' carriers had increased activity for both angry and fearful faces relative to neutral. Additionally, the response to angry faces was significantly greater in LA LA individuals compared to S' carriers and the response to fearful faces was significantly greater in S' carriers compared to LA LA individuals. These findings provide novel evidence for emotion-specific 5-HTTLPR effects on the response of a distributed set of brain regions including areas responsive to emotionally salient stimuli and critical components of the face-processing network. These findings provide additional insight into neurobiological mechanisms through which 5-HTTLPR genotype may affect personality and related risk for neuropsychiatric illness.

Face and emotion expression processing and the serotonin transporter polymorphism 5‐HTTLPR/rs22531

“…Previous behavior genetic studies on the relationship between the 5‐HTTLPR/rs25531 and FP, relying on single task paradigms had provided inconclusive results (Antypa et al ; Boll & Gamer ; Defrancesco et al ; Fisher et al ; Jonassen et al 2012a,b; Székely et al ). Therefore, the reported relationship between the 5‐HTTLPR/rs25531 genotype and the facial emotion and identity perception observed in the present study, when considering latent variables, is an important finding.…”

“…Results from studies on emotion recognition accuracy are inconsistent as well. Boll and Gamer () found a better general emotion recognition accuracy for the low as compared with the high expressing 5‐HTT group; other studies reported a better recognition accuracy in the low 5‐HTT group specifically for fear (Defrancesco et al ; Fisher et al ) or negative emotions in general (Antypa et al ); still others showed better recognition accuracy for sad and fearful faces in the high expressing 5‐HTT group (Jonassen et al 2012a,b; Székely et al ).…”

Convergent individual differences in visual cortices, but not the amygdala across standard amygdalar fMRI probe tasks

“…The latter have predominantly subtracted responses to non-threatening visual stimuli from responses towards either facial stimuli expressing aversive emotions or sets of more generally aversive scenes (Adolphs, 2008). A number of these tasks have been applied as probe tasks of amygdalar functioning in different patient groups (Broome et al, 2015), across individuals with different personality traits (Clauss et al, 2015; Kennis et al, 2013) and in studies of development and genetics (Fisher et al, 2015; Wu et al, 2016). …”

Understanding the impact of 5-HTTLPR, antidepressants, and acute tryptophan depletion on brain activation during facial emotion processing: A review of the imaging literature

“…Only 25 studies fulfilled the inclusion criteria for the purpose of the review. 22 reported brain activation differences associated with the 5-HTTLPR polymorphism (Battaglia et al, 2012;Bertolino et al, 2005;Canli et al, 2006Canli et al, , 2008Dannlowski et al, 2010;Domschke et al, 2012;Fisher et al, 2015Fisher et al, , 2014Hariri et al, 2005Hariri et al, , 2002Lee and Ham, 2008;Lonsdorf et al, 2011;O'Nions et al, 2011;Pezawas et al, 2005;Surguladze et al, 2012Surguladze et al, , 2008Thomason et al, 2010;Volman et al, 2013;Von dem Hagen et al, 2011;Walsh et al, 2012;Waring et al, 2014;Wiggins et al, 2014). Two of the 22 5-HTTLPR studies reported additionally TPH2 genotype related brain activation (Canli et al, 2008;Lee and Ham, 2008).…”

“…Unlike Lee and Ham who reported effects related to the single genes (Lee and Ham, 2008), Canli and colleagues reported an additive gene-gene effect of TPH2 with 5-HTTLPR alleles (Canli et al, 2008). Of the 25 studies, only eleven groups focused on the SNP rs25531 in their analyses, a functional polymorphism suggested to modulate the transcriptional efficacy of 5-HTTLPR (Canli et al, 2006;Costafreda et al, 2013;Dannlowski et al, 2010Dannlowski et al, , 2008Domschke et al, 2012;Fisher et al, 2015Fisher et al, , 2014O'Nions et al, 2011;Surguladze et al, 2012;Thomason et al, 2010;Wiggins et al, 2014). Two groups decided to follow a biallelic approach due to group size issues (Canli et al, 2006;Thomason et al, 2010).…”