Sleep endophenotypes of schizophrenia: slow waves and sleep spindles in unaffected first-degree relatives

Sleep spindles and slow waves are the main brain oscillations occurring in non-REM sleep. Several lines of evidence suggest that spindles are initiated within the thalamus, whereas slow waves are generated and modulated in the cortex. A decrease in sleep spindle activity has been described in Schizophrenia (SCZ), including chronic, early course, and early onset patients. In contrast, slow waves have been inconsistently found to be reduced in SCZ, possibly due to confounds like duration of illness and antipsychotic medication exposure. Nontheless, the implication of sleep spindles and slow waves in the neurobiology of SCZ and related disorders, including their heritability, remains largely unknown. Unaffected first-degree relatives (FDRs) share a similar genetic background and several neurophysiological and cognitive deficits with SCZ patients, and allow testing whether some of these measures are candidate endophenotypes. In this study, we performed sleep high-density EEG recordings to characterise the spatiotemporal features of sleep spindles and slow waves in FDRs of SCZ probands and healthy subjects (HS) with no family history of SCZ. We found a significant reduction of integrated spindle activity (ISAs) in FDRs relative to HS, whereas spindle density and spindle duration were not different between groups. FDRs also had decreased slow wave amplitude and slopes. Altogether, our results suggest that ISAs deficits might represent a candidate endophenotype for SCZ. Furthermore, given the slow wave deficits observed in FDRs, we propose that disrupted cortical synchronisation increases the risk for SCZ, but thalamic dysfunction is necessary for the disorder to fully develop.Diagnostics: Can sleep forewarn schizophrenia susceptibility?Sleep EEG recordings of schizophrenia patients’ relatives differ from healthy norms, suggesting a new hereditary biomarker of disease. Leading a collaboration of Italian and US scientists, the University of Milan’s Armando D’Agostino, Anna Castelnovo and Simone Sarasso compared the electrical activity of healthy subjects’ brains during sleep to that of first-degree relatives of schizophrenia patients. The team found a significant reduction in a parameter related to the amplitude of “sleep spindles,” one of the two major types of brainwaves in non-REM sleep, in the relatives’ brains. However, the density of sleep spindles—a schizophrenia-associated trait—was unaffected in relatives. The authors suggest that reduced sleep spindle amplitude may help to indicate an individual’s risk of developing schizophrenia. Other EEG features from relatives suggest a communication impairment between neuron groups, which may also predispose the illness.