22q11 deletion syndrome, CACNA1A mutations, and sleep deprivation: from theta waves to the cognitive impairments of schizophrenia

Background: Sleep disorders and schizophrenia have a reciprocal relationship: the poorer the sleep quality, the more severe the psychotic symptoms, and conversely, improved sleep quality appears to be associated with an improvement in psychotic symptoms. The physiological mechanisms underlying this interaction are currently unknown.

Objectives: To describe one of the physiological mechanisms underlying this interaction, to see the consequences for cognition and to derive possibilities for therapeutic action.

Methods: We will review three relevant human models for studying the physiology of schizophrenic spectrum disorders: 22q11 deletion syndrome, CACNA1A mutations, and sleep deprivation. We will begin by examining the correlation between sleep quality and the extent of theta waves on resting-state EEG, on the one hand, and symptoms and cognition, on the other. Secondly, we will see the pharmacological arguments suggesting that this correlation does not appear to be due to chance before proposing a physiological explanation: the intrusion of local sleep islands into brain function.

Therapeutic consequences: This correlation between the importance of theta waves in the resting-state EEG of patients on the one hand and their cognitive deficits and symptoms on the other could make it possible to improve the latter by using active substances whose action on neuronal processes is reflected by the reduction of theta waves in the resting-state EEG.

Conclusion: The link between cognitive impairment and increased resting theta waves is partially confirmed by pharmacological evidence, as is the possibility of improving cognitive impairment using active substances that normalize this increase. If it were fully confirmed by appropriate clinical trials, this would open up new perspectives for changing the management of schizophrenia spectrum disorders.