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1113 THE EFFECTS OF ESZOPICLONE ON SLEEP SPINDLES AND MEMORY CONSOLIDATION IN SCHIZOPHRENIA: A DOUBLE-BLIND RANDOMIZED TRIAL
Abstract   Open access

1113 THE EFFECTS OF ESZOPICLONE ON SLEEP SPINDLES AND MEMORY CONSOLIDATION IN SCHIZOPHRENIA: A DOUBLE-BLIND RANDOMIZED TRIAL

B Baran, C Demanuele, T C Vuper, B Seicol, R A Fowler, D Correll, E Parr, C E Callahan, A Morgan, R Stickgold, …
Sleep (New York, N.Y.), Vol.40(suppl_1), pp.A415-A415
04/28/2017
DOI: 10.1093/sleepj/zsx050.1112
url
https://doi.org/10.1093/sleepj/zsx050.1112View
Published (Version of record) Open Access

Abstract

Abstract Introduction: Patients with schizophrenia (SZ) have a specific deficit in sleep spindles that correlates with impaired memory consolidation and symptom severity. In a small placebo-controlled pilot study we found that eszopiclone, a non-benzodiazepine hypnotic drug that acts on GABAA receptors in the thalamus where sleep spindles are generated, increased spindles in SZ but its effect on memory consolidation was not significant. Here we employed a more powerful cross-over design and recruited a larger sample to investigate the effects of eszopiclone on spindle activity and sleep-dependent memory consolidation. Methods: Chronic, medicated patients with SZ (n=26) and demographically-matched healthy controls (n=29) were randomly assigned to either placebo first or 3 mg of eszopiclone first conditions separated by one week. Each condition included two consecutive nights of high-density EEG polysomnography. Consolidation of motor procedural memory was measured by the motor sequence task (MST). Participants were trained before sleep on the second night and tested upon awakening. Spindles were detected by a wavelet-based algorithm and examined in relation to overnight changes in MST performance. Results: On placebo, patients showed consistent, widespread reductions in spindle density that reached significance in a parietal cluster(p=.04). In both groups, eszopiclone increased spindle density across channels(p<.001) but more for patients than controls in parietal regions(p=.03). Overnight MST improvement correlated significantly with sleep spindle density in both placebo(r=.36, p=.008) and eszopiclone(r=.34, p=.01) conditions and this did not differ by group. While both groups showed significant memory consolidation on placebo, eszopiclone did not increase it in either group. Conclusion: While eszopiclone significantly increased spindles, and spindles correlated with memory, eszopiclone did not improve memory. This may reflect that memory consolidation relies not only on spindles, but also on their coordination with other NREM oscillations. This hypothesis is supported by recent findings that both spindle density and the coordination of spindles with slow waves predict sleep-dependent memory consolidation in SZ. Thus, interventions to improve memory in SZ may need to both increase spindle density and preserve or enhance their coordination with NREM oscillations. Support (If Any): This research was supported by 1R01MH092638 to DSM and RS, and NIH-NHLBI 5T32HL007901-17 to BB.

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