A burgeoning literature suggests that sleep spindles mediate sleep-dependent memory consolidation and cognitive function more generally. At the same time, several recent studies show that sleep spindles are dramatically reduced in SZ. Cognitive deficits are a core feature of schizophrenia (SZ) that underlie significant functional disability and effective treatments are lacking. Previous work from our laboratories links the sleep spindle deficit with an impairment of sleep-dependent memory consolidation, IQ and executive function in SZ, and suggests that it is treatable. But it is unclear whether this sleep spindle deficit is present early in SZ, and whether it reflects a core disturbance central to its pathophysiology and familial risk of illness. In this study, we will examine sleep spindles, their relationship to memory consolidation and cognition more generally, and their neural underpinnings in early-course patients both with SZ (E-SZ; n=30), and with other psychoses (E-NSZ; n=30), in young relatives of SZ patients at familial high risk for SZ (FHR; n=60) and in healthy comparison (HC) subjects matched for age, sex and parental socioeconomic status. We hypothesize (i) that E-SZ and FHR, but not E-NSZ, will show reduced spindles compared with HC; (ii) that spindle number and density will correlate with sleep-dependent memory consolidation, IQ and overall cognitive function in all groups, and that deficient sleep spindles will correlate with positive and prodromal symptoms in E-SZ and FHR; and (iii) that during the sleep that follows motor task learning, HC and E-NSZ, but not E-SZ or FHR participants, will show increased spindle density and coherence, specifically in the motor network. We also predict that reduced spindle density will correlate with a reduction in thalamocortical functional and structural connectivity. Our hypotheses, if confirmed, will help establish the sleep spindle deficit as (i) an endophenotype of SZ, which can serve as a biomarker of familial risk (for studying the etiopathology of SZ), and (ii) a target for novel treatments of cognitive impairment.
Cognitive impairments are a core, highly disabling and treatment resistant feature of schizophrenia. Patients with schizophrenia also have a specific deficit in sleep spindles that is related to their impairment in memory consolidation. We propose to examine sleep spindles, their relationship to memory consolidation, and their neural underpinnings, in early-course patients with schizophrenia and in young at-risk relatives of schizophrenia patients to determine whether spindle deficits are central to the pathophysiology and familial susceptibility to schizophrenia and to identify targets for treatment to remediate cognition.
