Schizophrenia-associated variation at ZNF804A correlates with altered experience-dependent dynamics of sleep slow waves and spindles in healthy young adults

Ullrich Bartsch*, Laura J Corbin, Charlotte Hellmich, Michelle Taylor, Kayleigh Easey, Claire F Durant, Hugh M. Marston, Nicholas John Timpson, Matt W Jones

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

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Abstract

The rs1344706 polymorphism in ZNF804A is robustly associated with schizophrenia and schizophrenia is, in turn, associated with abnormal non-rapid eye movement (NREM) sleep neurophysiology. To examine whether rs1344706 is associated with intermediate neurophysiological traits in the absence of disease, we assessed the relationship between genotype, sleep neurophysiology, and sleep-dependent memory consolidation in healthy participants. We recruited healthy adult males with no history of psychiatric disorder from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. Participants were homozygous for either the schizophrenia-associated ‘A’ allele (N=22) or the alternative ‘C’ allele (N=18) at rs1344706. Actigraphy, polysomnography (PSG) and a motor sequence task (MST) were used to characterize daily activity patterns, sleep neurophysiology and sleep-dependent memory consolidation. Average MST learning and sleep-dependent performance improvements were similar across genotype groups, albeit more variable in the AA group. During sleep after learning, CC participants showed increased slow-wave (SW) and spindlemplitudes, plus augmented coupling of SW activity across recording electrodes. SW and spindles in those with the AA genotype were insensitive to learning, whilst SW coherence decreased following MST training. Accordingly, NREM neurophysiology robustly predicted the degree of overnight motor memory consolidation in CC carriers, but not in AA carriers. We describe evidence that rs1344706 polymorphism in ZNF804A is associated with changes in the coordinated neural network activity that supports offline information processing during sleep in a healthy population. These findings highlight the utility of sleep neurophysiology in mapping the impacts of schizophrenia-associated common genetic variants on neural circuit oscillations and function.
Original languageEnglish
Article numberzsab191
JournalSleep
Early online date30 Jul 2021
DOIs
Publication statusE-pub ahead of print - 30 Jul 2021

Structured keywords

  • ALSPAC

Keywords

  • psychosis
  • schizophrenia
  • genetics
  • sleep
  • slow wave
  • spindle
  • motor sequence task

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