0064 Sleep Loss Affects Item and Source Memory Differentially as a Function of Serotonin Transporter (5-HTTLPR) Genotype

Abstract Introduction Remembering relationships between items (information) and the contexts (sources) in which they are framed is crucial for everyday functioning. Total sleep deprivation (TSD) impairs this ability, with evidence suggesting that TSD affects source memory even when items are remembered. Source memory deficits imply problems with associative memory, which relies on hippocampal functioning, known to be altered by TSD. Serotonin is highly expressed in the hippocampus, is influenced by TSD, and may be part of a mechanism by which TSD degrades source memory. We investigated the association between 5-HTTLPR, a functional length polymorphism of the human serotonin transporter gene (SLC6A4), and item and source memory during TSD. Methods N=34 healthy adults (ages 27.3±4.9y; 18 female) participated in a 4-day/3-night laboratory TSD study. Participants underwent 38h TSD, preceded and followed by 10h sleep opportunities. At baseline and 24h later during TSD, they completed an item/source memory task. Participants listened to a list of 60 words each presented by a male or female speaker (study phase). They were then tested for recognition of the words (items) out of 60 old and 60 new words presented visually, and were asked to identify the corresponding speakers (sources, male or female). Results The genotype distribution was in Hardy-Weinberg equilibrium (P=0.34), with 35.3% long/long, 41.2% long/short, 23.5% short/short. Mixed-effects ANOVA showed a significant adverse effect of TSD for both item recognition (P< 0.001) and source recognition (P< 0.001), where TSD degraded source memory even when item recognition was accurate. There were no 5-HTTLPR genotype effects on item memory. However, there was a significant main effect for genotype on source memory (P=0.019), and a genotype by TSD interaction (P=0.018). For accurately recognized items, source memory was largely preserved for the short/short genotype but impaired for carriers of the long allele, and especially the long/long genotype. Conclusion 5-HTTLPR genotype predicted source memory deficits from TSD, distinct from item memory deficits unaffected by genotype, which confirms that item and source memory deficits due to TSD are dissociable. Furthermore, TSD’s impact on binding of items and sources in memory may be mediated by hippocampal serotonin. Support (if any) NIH R21CA167691, WSU Anthony Marchionne and Foundry10 Bridge fellowships