ORIGINAL RESEARCH ARTICLE published: 10 May 2012 doi: 10.3389/fpsyg.2012.00139 Influence of threat and serotonin transporter genotype on interference effects Agnes J. Jasinska 1,2 *, S. Shaun Ho 3 , Stephan F.Taylor 3 , Margit Burmeister 3,4,5 , Sandra Villafuerte 3,5 and Thad A. Polk 2 1 Michigan Institute for Clinical and Health Research, University of Michigan, Ann Arbor, MI, USA 2 Department of Psychology, University of Michigan, Ann Arbor, MI, USA 3 Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA 4 Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA 5 Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA Edited by: MattieTops, University of Leiden, Netherlands Reviewed by: Henk Van Steenbergen, Leiden University, Netherlands Roman Osinsky, University of Wuerzburg, Germany *Correspondence: Agnes J. Jasinska, Department of Psychology, University of Michigan, 1012 East Hall, 530 Church Street, Ann Arbor, MI 48109-2215, USA. e-mail: jasinska@umich.edu Emotion-cognition interactions are critical in goal-directed behavior and may be disrupted in psychopathology. Growing evidence also suggests that emotion-cognition interactions are modulated by genetic variation, including genetic variation in the serotonin system.The goal of the current study was to examine the impact of threat-related distracters and serotonin transporter promoter polymorphism (5-HTTLPR/rs25531) on cognitive task performance in healthy females. Using a novel threat-distracter version of the Multi-Source Interfer- ence Task specifically designed to probe emotion-cognition interactions, we demonstrate a robust and temporally dynamic modulation of cognitive interference effects by threat- related distracters relative to other distracter types and relative to no-distracter condition. We further show that threat-related distracters have dissociable and opposite effects on cognitive task performance in easy and difficult task conditions, operationalized as the level of response interference that has to be surmounted to produce a correct response. Finally, we present evidence that the 5-HTTLPR/rs25531 genotype in females modulates sus- ceptibility to cognitive interference in a global fashion, across all distracter conditions, and irrespective of the emotional salience of distracters, rather than specifically in the presence of threat-related distracters.Taken together, these results add to our understanding of the processes through which threat-related distracters affect cognitive processing, and have implications for our understanding of disorders in which threat signals have a detrimental effect on cognition, including depression and anxiety disorders. Keywords: cognition, emotion, interference resolution, threat, serotonin transporter gene, 5-HTTLPR, MSIT INTRODUCTION The ability to successfully carry out a task despite interference from task-irrelevant stimuli is a crucial requirement for goal-directed behavior. According to accepted models of selective attention and cognitive-control, task-irrelevant stimuli interfere with cog- nitive task performance by competing with task-relevant stimuli for attentional and response-selection resources (Desimone and Duncan, 1995; Miller and Cohen, 2001). However, the impact of distracters on task performance – or conversely, our ability to resist interference from these distracters – can vary considerably, depending on the attributes of the distracters and the attributes of the task itself (Lavie, 2005), as well as on individual differences in susceptibility to various distracters. Critically, with respect to distracter attributes, such interference can come from both neutral and emotionally salient stimuli, high- lighting the fact that emotional and cognitive processes are closely interrelated, giving rise to complex and bidirectional emotion- cognition interactions (Davidson, 2003; Blair et al., 2007). In particular, if neutral distracters impair task performance, threat- related distracters should be even more effective in high-jacking attention and interfering with the task at hand due to the preferential processing of threat stimuli over non-threat stimuli in the brain. This rapid and automatic processing of threat signals is possible because the amygdala receives threat-related informa- tion through a fast subcortical pathway as well as through a slower cortical route (Romanski and LeDoux, 1992; Morris et al., 1999), a finding supported by functional neuroimaging studies show- ing that the amygdala responds to threat stimuli that are outside of attentional focus or conscious awareness (Whalen et al., 1998; Vuilleumier et al., 2001). From an evolutionary perspective, in humans as in many other species, such preferential processing of potential threat signals serves the adaptive function of facilitat- ing rapid threat detection and fight-or-flight responses essential for survival (Ohman and Mineka, 2001). However, although sup- ported by some studies (Vuilleumier et al., 2001; Dolcos and McCarthy, 2006; Blair et al., 2007; Mitchell et al., 2008), such increased distractability by threat-related distracters relative to neutral distracters in behavioral measures has not been consis- tently demonstrated in healthy subjects (Bar-Haim et al., 2007), suggesting that additional modulatory factors may be at play. Neuroimaging evidence also suggests that the effects of threat distracters on interference processing may dynamically change www.frontiersin.org May 2012 |Volume 3 | Article 139 | 1