Association of the serotonin transporter gene promoter region (5-HTTLPR) polymorphism with biased attention for emotional stimuli.

Abstract

A deletion polymorphism in the serotonin transporter-linked polymorphic region (5-HTTLPR) has been associated with vulnerability to affective disorders, yet the mechanism by which this gene confers vulnerability remains unclear. Two studies examined associations between the 5-HTTLPR polymorphism and attentional bias for emotional stimuli among non-depressed adults. Biased attention, attention engagement, and difficulty with attention disengagement were assessed with a spatial cueing task using emotional stimuli. Results from Study 1 (N = 38) indicated that short 5-HTTLPR allele carriers experienced greater difficulty disengaging their attention from sad and happy stimuli compared to long allele homozygotes. Study 2 participants (N = 144) were genotyped for the 5-HTTLPR polymorphism, including single nucleotide polymorphism (SNP) rs25531 in the long allele of the 5-HTTLPR. Consistent with Study 1, individuals homozygous for the low expressing 5-HTTLPR alleles (i.e., S and L G ) experienced greater difficulty disengaging attention from sad, happy, and fear stimuli than high expressing 5-HTTLPR homozygotes. Since this association exists in healthy adults, it may represent a susceptibility factor for affective disorders that becomes problematic during stressful life experiences. Keywords genetic association; depression vulnerability; serotonin transporter; information processing Individuals who inherit the low expressing variant of the serotonin transporter-linked polymorphic region (5-HTTLPR) of the serotonin transporter gene (SLC6A4) and experience Correspondence concerning this article should be addressed to Christopher G. Beevers, Department of Psychology, University of Texas at Austin, 1 University Station, A8000, Austin, TX 78712. beevers@psy.utexas.edu. Publisher's Disclaimer: The following manuscript is the final accepted manuscript. It has not been subjected to the final copyediting, fact-checking, and proofreading required for formal publication. It is not the definitive, publisher-authenticated version. The American Psychological Association and its Council of Editors disclaim any responsibility or liabilities for errors or omissions of this manuscript version, any version derived from this manuscript by NIH, or other third parties. The published version is available at www.apa.org/pubs/journals/abn. NIH Public AccessAuthor Manuscript J Abnorm Psychol. Author manuscript; available in PMC 2010 August 1. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript significant life stress appear to be at greater risk for depression than people who inherit two copies of the high expressing 5-HTTLPR allele (e.g., Caspi et al., 2003;Kendler, Kuhn, Vittum, Prescott, & Riley, 2005). These landmark studies have stimulated research aimed at understanding why the low expressing 5-HTTLPR variant putatively increases sensitivity to life stress and, in turn, increases vulnerability to depression. One possibility is that the 5-HTTLPR polymorphism biases the processing of emotional information. Ther...

Understanding vulnerability for depression from a cognitive neuroscience perspective: A reappraisal of attentional factors and a new conceptual framework

“…It has been proposed that the short allele variant, associated with a reduced 5-HT function, causes increased brain responses to negative stimuli (Bethea et al, 2004). Beevers, Wells, Ellis, and McGeary (2009) also demontrated that variations in the 5-HT polymorphism are associated with attentional processing of emotional information in a nonclinical population. It was found that short allele carriers show impaired disengagement from emotional material.…”

Differential Effects of 5-HTTLPR Genotypes on Inhibition of Negative Emotional Information Following Acute Stress Exposure and Tryptophan Challenge

“…Hence, attentional bias for negative information is a hallmark feature of MDD (see Scher et al, 2005), which relates to impaired cognitive inhibition toward negative emotional material (Goeleven et al, 2006;Gotlib et al, 2005;De Raedt and Koster, 2010). In support, 5-HT is implicated in decreased attentional control over negative stimuli by modulating prefrontal-amygdala connectivity (see Cools et al, 2008), and S/S show enhanced emotional amygdala responses (Hariri and Holmes, 2006) and impaired disengagement to emotional information (Beevers et al, 2009). …”

Acute responsivity of the serotonergic system to S-citalopram and positive emotionality – The moderating role of the 5-HTTLPR

“…This means that high scores in this scale for positive emotionality would indicate a heightened responsiveness to emotional stimuli. Specifically, such an increased reactivity for positive as well as negative emotional stimuli has been demonstrated in s-allele-carriers several times (e.g., Canli et al, 2005;Herrmann et al, 2007;Beevers et al, 2009). One could, insofar, speculate that the MPQ more closely depicts emotional responsiveness and reflects its biological underpinnings more adequately.…”

“…Alongside an altered attention to unpleasant stimuli (Pergamin-Hight et al, 2012), some studies demonstrated that s-allele-carriers, unlike ll-homzygotes, also selectively attend to pleasant stimuli (Beevers et al, 2009(Beevers et al, , 2011Fox et al, 2011). Neuroimaging studies underpin this association, showing heightened neuronal activation in response to negatively- (Munafo et al, 2008) as well as positively-valenced stimuli in s-allele-carriers (Canli et al, 2005;Herrmann et al, 2007;Klucken et al, 2012).…”