0263 IMPACT OF THE 5-HTTLPR POLYMORPHISM ON NEURAL RESPONSES TO IMPLICIT THREAT AND FEAR LEARNING AND MEMORY AFTER SLEEP DEPRIVATION

Abstract

The short (s) allele variant of the serotonin transporter polymorphism 5-HTTLPR, compared to the long (l) allele variant, has been associated with heightened stress reactivity. We explored the moderating impact of this polymorphism on neural correlates of implicit threat detection and fear-associated learning and memory following total and partial sleep deprivation in healthy young adults. 134 participants spent 3 night in the laboratory after being genotyped for 5-HTTLPR. After a baseline night, participants were randomized to total sleep deprivation (SD, n = 35), sleep restriction (SR or half the normal sleep time, n=40), or normal sleep (NS, n = 43). The following morning, the participants completed a fear conditioning and extinction protocol. Fear extinction recall was tested in the evening. Neural responses to implicit threat cues were assessed in the evening before and after randomization. BOLD signals in the amygdala and ventromedial prefrontal cortex (vmPFC) were compared between s/s, s/l, and l/l carriers. ROI analyses were conducted using SPM8 and SPSS. No significant Sleep Group X Genotype interaction was found for fear conditioning, extinction, or extinction recall for the amygdala or vmPFC. For the threat task, a main effect of Genotype was detected for the right amygdala (F(2,129) =3.24, p < 0.05) at baseline, where the s/l group showed lower BOLD activation in response to threatening vs. neutral cues than the l/l and s/s groups. Following the sleep manipulation, the three genotypes no longer differed. The 5-HTTLPR polymorphism does not moderate neural fear-related responses. Heterozygotes (s/l carriers) showed the greatest BOLD reactivity to threat cues in the right amygdala at baseline, but this effect was absent following the sleep manipulation. Sleep loss may override the impact of genotype on neural reactivity to salient cues. This work was supported by the Department of Defense Congressionally Directed Medical Research Program Military Operational Medicine Research Program (MOMRP; Log#11293006). The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the US Army or of the US Department of Defense.