NREM sleep oscillations and their relations with sleep-dependent memory consolidation in early course psychosis and first-degree relatives

Abstract

Sleep spindles are believed to mediate sleep-dependent memory consolidation, particularly when coupled to neocortical slow oscillations. Schizophrenia is characterized by a deficit in sleep spindles that correlates with reduced overnight memory consolidation. Here, we examined sleep spindle activity, slow oscillation-spindle coupling, and both motor procedural and verbal declarative memory consolidation in early course, minimally medicated psychosis patients and non-psychotic first-degree relatives. Using a four-night experimental procedure, we observed significant deficits in spindle density and amplitude in patients relative to controls that were driven by individuals with schizophrenia. Schizophrenia patients also showed reduced sleep-dependent consolidation of motor procedural memory, which correlated with spindle density. Contrary to expectations, there were no group differences in the consolidation of declarative memory on a word pairs task. Nor did the relatives of patients differ in spindle activity or memory consolidation compared with controls, however increased consistency in the timing of SO-spindle coupling were seen in both patient and relatives. Our results extend prior work by demonstrating correlated deficits in sleep spindles and sleep-dependent motor procedural memory consolidation in early course, minimally medicated patients with schizophrenia, but not in first-degree relatives. This is consistent with other work in suggesting that impaired sleep-dependent memory consolidation has some specificity for schizophrenia and is a core feature rather than reflecting the effects of medication or chronicity. Statement of significanceWe investigated sleep neurophysiology and memory consolidation in minimally-medicated, early course psychosis patients and unaffected first-degree relatives of patients in a four-night study. Early-course schizophrenia patients had a sleep spindle deficit that correlated with reduced procedural memory consolidation. Although first-degree relatives did not show any deficit in spindles or memory consolidation, the spindles of both relatives and patients showed increased consistency of the temporal coupling of spindles with slow oscillations compared with controls. These results suggest that sleep spindle and memory consolidation deficits are a core feature of schizophrenia. Spindle deficits may be a biomarker of schizophrenia modifiable by treatment, and motivate the development of targeted novel interventions.