Sleep Deprivation Mimics Psychosis

Nancy A. Melville

July 21, 2014

After 24 hours of sleep deprivation, healthy individuals show symptoms of psychosis similar to those observed in schizophrenia, new research shows.

While underscoring the known adverse effects of severe insomnia on brain function, the study is the first to show sleep deprivation to trigger a key biomarker of psychosis that is important in the research of antipsychotic drugs ― a reduction in prepulse inhibition of the acoustic startle response.

"This strong main effect indicates that sleep deprivation might be an alternative method to the approach to pharmacologically induce deficits in prepulse inhibition in healthy volunteers," the authors write.

The study was published July 2 in the Journal of Neuroscience.

Reliable Biomarker

Reduced prepulse inhibition is a reliable symptom not just of schizophrenia but also of schizophrenialike personality disorders, and it is seen in psychosis-prone healthy individuals. Specifically, it involves a reduced response to a strong stimulus, or pulse, if the stimulus is preceded with a weaker stimulus, or prepulse.

Although the biomarker is often used in the research of antipsychotic compounds in animals, it is hard to mimic in humans without pharmacologic or experimental methods.

"If the prepulse inhibition-decreasing effect of sleep deprivation can be replicated in humans, the sleep deprivation paradigm could prove a powerful model system of psychosis with strong clinical relevance," the authors write.

For the proof-of-concept study, lead author Ulrich Ettinger, MD, and colleagues with the Cognitive Psychology Unit, Department of Psychology, University of Bonn, Germany, evaluated acoustic prepulse inhibition and self-reported psychosislike symptoms in 24 healthy volunteers following a normal night's sleep and after a night of complete sleep deprivation.

Participants were kept awake through the night with various activities, including conversation, movies, brief walks, and games.

After being kept up all night, participants were interviewed and were also assessed for prepulse inhibition, which involved exposure to a loud noise emitted through headphones and recording of the startle response with the use of electrodes to measure contraction in facial muscles.

Good Model of Schizophrenia

The results showed a robust effect in terms of significantly decreased prepulse inhibition associated with sleep deprivation (P = .001), and the severe insomnia also induced perceptual distortions, cognitive disorganization, and anhedonia (for all, P < .02).

Importantly, sleep deprivation did not affect the degree or habituation of the startle response (for all, P > .13), indicating no effects of sleep deprivation on pulse only amplitudes.

The identification of a prepulse inhibition in relation to sleep deprivation is important because it represents a true symptom of psychosis that cannot be "faked," Dr. Ettinger told Medscape Medical News.

"It's a cross-species phenomenon, and we already know a lot about it ― for example, that it is impaired in schizophrenia, that it can be impaired in rats with ketamine/amphetamine, and that these impairments can be reversed with atypical antipsychotics."

"Thus, sleep deprivation may be a very good model of schizophrenia, in particular when combined with prepulse inhibition."

Sleep disturbances are common in people with schizophrenia, and severe insomnia is associated with exacerbations of the condition, leading to additional symptoms, but Dr. Ettinger said he was surprised to see the extent of effects of the loss of just 1 night of sleep even among healthy individuals.

"A single night of sleep deprivation may not at first seem like a particularly drastic intervention, and can for instance occur with students out partying or people working through the night; therefore, we were surprised to see such statistically significant increases in self-ratings of all 3 dimensions of schizophrenia ― thought disorder, perceptual aberrations, and negative symptoms."

Out on a Limb?

Commenting on the study for Medscape Medical News, neurologist Donn Dexter, MD, said the effects of extreme insomnia have previously been associated with schizophrenialike symptoms.

"Prior research shows that prolonged sleep deprivation can actually cause a syndrome indistinguishable from paranoid schizophrenia. However, it is probably harder to get approval for such studies in current settings," said Dr. Dexter, a physician in the Neurology Department and Sleep Disorders Center at the Mayo Clinic Health System, in Eau Claire, Wisconsin.

Some important potential confounders, however, may limit the utility of the findings, he suggested.

"The findings are interesting and, in a limited application, probably have real value, but I would be very careful about extending this too far," he said.

"There are too many possible confounders, including that it's a small study with limited age groups, you're only looking at 1 biomarker and just 1 night of sleep deprivation, so it's kind of going out on a limb if you make too broad of a statement about it."

The authors and Dr. Dexter have disclosed no relevant financial relationships.

J Neurosci. 2014;34:9134-9140. Abstract

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