Altered Sleep Oscillations as Neurophysiological Biomarkers of Schizophrenia.

Sleep spindles and slow waves are the two main oscillatory activities occurring during nonrapid eye movement (NREM) sleep. Here, we will first describe the electrophysiological characteristics of these sleep oscillations along with the neurophysiological and molecular mechanisms underlying their generation and synchronization in the healthy brain. We will then review the extant evidence of deficits in sleep spindles and, to a lesser extent, slow waves, including in slow wave-spindle coupling, in patients with Schizophrenia (SCZ) across the course of the disorder, from at-risk to chronic stages. Next, we will discuss how these sleep oscillatory deficits point to defects in neuronal circuits within the thalamocortical network as well as to alterations in molecular neurotransmission implicating the GABAergic and glutamatergic systems in SCZ. Finally, after explaining how spindle and slow waves may represent neurophysiological biomarkers with predictive, diagnostic, and prognostic potential, we will present novel pharmacological and neuromodulatory interventions aimed at restoring sleep oscillatory deficits in SCZ, which in turn may serve as target engagement biomarkers to ameliorate the clinical symptoms and the quality of life of individuals affected by this devastating brain disorder.