Variation of 5-HTTLPR and deficits in emotion regulation: A pathway to risk?

Abstract

Genetic variation in the serotonergic system within the brain has been a significant focus of psychiatric research over the last several decades. In particular, the serotonin transporter (5-HTT) gene (SLC6A4) has been tied to early emotion processing biases. However, a clear understanding of how genetic variation of SLC6A4 may influence clinically salient emotional phenomena is still elusive. In this investigation, we focused on examining variation in the 5-HTT-linked polymorphic region (5-HTTLPR; including the single nucleotide polymorphism rs25531 which alters genotype interpretation) and real-time emotion responses evoked in the laboratory using a paradigm designed to spontaneously induce emotion regulation. Across 2 studies we show that for healthy individuals with 2 copies of the functional short (S=) allele there is weakened downregulation of negative emotion. In addition, we found greater electrodermal responses as well as both negative and positive emotion in association with the S= allele in 1 of the 2 samples. These findings provide evidence that the S= allele may promote system-wide heightened emotional reactivity in healthy subjects. Both phenomena, observed here in a healthy population, are strongly linked to the development of psychiatric disease. As such, these findings have implications for S= carriers' vulnerability to affective disorders, as well as suggest potential targets for future clinical investigation.

Emotion Regulation: A Transdiagnostic Perspective on a New RDoC Domain

“…For example, Gilman and colleagues (2015) examined variation in the 5-HTTLPR and emotion responses to a task designed to spontaneously induce emotion regulation; they found that for individuals with two copies of the short allele of this gene, there was weakened downregulation of negative emotion, indicating that perhaps these individuals (relative to those without two copies of the short allele) are more vulnerable to affective disorders. In a separate study, Miu and colleagues (2013) found evidence for reappraisal as a mediator of the relationship between the 5-HTTLPR gene and social anxiety symptoms, such that individuals with two copies of the short allele reported increased social anxiety symptoms and decreased use of reappraisal.…”

“…5-HTT=serotonin transporter gene; COMT=catechol-O-methyltransferase gene; PFC=prefrontal cortices; ACC=anterior cingulate cortex; EMG=electromyography; EEG=electroencephalogram; ERQ=Emotion Regulation Questionnaire; DERS = Difficulties in Emotion Regulation Scale; CERQ = Cognitive Emotion Regulation Questionnaire; ERI = Emotion Regulation Interview; ERP-R=Emotion Regulation Profile-Revised; EROS=Emotion Regulation of Others and Self; IERQ=Interpersonal Emotion Regulation Questionnaire; 1 (Gilman et al, 2015); 2 (Miu et al, 2013); 3 (Nikolova, Davis, & Hariri, 2014); 4 (Kim et al, 2011); 5 (Salgado-Pineda et al, 2005); 6 (Canli & Lesch, 2007); 7 (Outhred et al, 2015); 8 (Hariri & Holmes, 2006); 9 (Crockett et al, 2008); 10 (Quirin et al, 2011); 11 (Lam et al, 2009); 12 (Poon et al, this issue); 13 (Walker et al, 2013); 14 (Miller et al, 2005); 15 (Banks et al, 2007); 16 (Etkin & Schatzberg, 2011); 17 (Marusak et al, 2015); 18 (Buhle et al, 2014); 19 (Kohn et al, 2014); 20 (Ochsner et al, 2002); 21 (Etkin, Egner, Peraza, Kandel, & Hirsch, 2006b); 22 (Etkin et al, 2010); 23 (Etkin & Wager, 2007); 24 (Phillips et al, 2003); 25 (Gross, 1998a); 26 (Gross & Levenson, 1993); 27 (Mauss et al, 2007); 28 (Dan-Glauser & Gross, 2015); 29 (Roberts et al, 2008); 30 (Giuliani...…”

Suppression mediates the effect of 5‐HTTLPR by stress interaction on depression

“…Indeed, some studies demonstrated a link between the S allele and a difficulty disengaging from emotional stimuli (Beevers, Marti, Lee et al . ; Beevers, Wells, Ellis, McGeary, ; Gilman, Latsko, Matt et al ., ).…”

“…Thus, heightened emotional reactivity and deficits in emotion regulation in S allele carriers have been shown by Gilman et al . (). Kochanska, Philibert and Barry () using a longitudinal design showed that children who carried a short 5‐HTTLPR allele, developed poor regulatory capacities if they were insecurely attached.…”

“…Thus, several studies have linked the S allele with reduced PFC-amygdala connectivity (Beevers, Pacheco, Clasen, McGeary & Schnyer, 2010;Gillihan, Rao, Wang et al, 2010;Heinz, Braus, Smolka et al, 2005;Pezawas et al, 2005), suggesting that individuals with at least one S allele may have difficulty down-regulating heightened emotional responses. Indeed, some studies demonstrated a link between the S allele and a difficulty disengaging from emotional stimuli (Beevers, Marti, Lee et al 2011;Beevers, Wells, Ellis, McGeary, 2009a;Gilman, Latsko, Matt et al, 2015).…”