Sleep disturbances are consistently high throughout the course of psychosis — with later stages associated with distinctive brain wave activity during sleep, a new review and meta-analysis shows.
For example, compared with their healthy peers, participants in a chronic psychosis stage had reduced density, amplitude, and duration of spindles — or bursts of brainwave activity during sleep identified by electroencephalography (EEG).
“The results suggest sleep could be an important target [and] an area of research and clinical intervention that could make a difference” in the lives of patients at risk for psychosis, study investigator Fabio Ferrarelli, MD, PhD, associate professor of psychiatry and director of the Sleep and Schizophrenia Program, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, told Medscape Medical News.
The findings were published online January 18 in JAMA Psychiatry.
“Window Of Opportunity”
Researchers separate psychosis into stages. During the “clinically high-risk for psychosis” (CHR-P) stage, patients have milder symptoms but do not have a diagnosable psychotic disorder. Those in the early psychosis (EP) stage have had a first episode of psychosis. When they reach a cut-off, often at 5 years, they are considered to have chronic psychosis (CP).
Previous studies have shown that altered sleep often precedes a psychotic episode in early psychosis, and disrupted sleep contributes to predicting transition to psychosis in youth at risk for the condition. Individuals with CP commonly report sleep disturbances, such as insomnia.
Following a literature search, the investigators for this current meta-analysis selected 21 studies assessing sleep disturbance prevalence in 5135 patients. They also selected 39 studies measuring sleep alterations subjectively (for example, sleep quality) and/or objectively (for example, sleep architecture and sleep oscillation) in 1575 patients and 977 healthy controls.
The included studies measured the prevalence of sleep disturbances and/or sleep characteristics at different psychosis stages using polysomnography, EEG, actigraphy, or self-reports.
The pooled prevalence of sleep disturbances was 50% across clinical stages (95% CI, 40% – 61%). The prevalence was 54% in CHR-P, 68% in EP, and 44% in CP.
The prevalence of insomnia as the primary sleep disturbance was 34% of pooled cases and 48% of the EP group and 27% of the CP group.
“What’s interesting is the rate of sleep disturbances is relatively stable across stages,” said Ferrarelli. “This is important because you have a window of opportunity to do some early intervention in people who are at risk that can prevent things from getting worse.”
He suggests clinicians screen for insomnia in early-course patients and perhaps recommend cognitive behavioral therapy (CBT) for insomnia. As well, they should promote sleep hygiene measures for at-risk patients, including such things as avoiding caffeine, alcohol, and screen time before bedtime and adopting a regular sleep pattern.
“These are people at risk, which means they have a 20%-30% chance of eventually developing a psychotic disorder,” said Ferrarelli. “Maybe disrupted sleep is one of the factors that can make a difference.”
Altered Sleep Architecture
To compare sleep quality between clinical and control groups, studies used total scores on the Pittsburgh Sleep Quality Index (PSQI), where a score over 5 indicates a sleep problem.
There was a significant standardized mean difference (SMD) in pooled cases vs controls (SMD, 1.0; 95% CI, 0.7 – 1.3; P < .001). Each clinical group showed poorer sleep quality compared with controls.
When assessing sleep architecture abnormalities, stage-specific case-control comparisons showed these were driven by EP and CP stages.
Altered sleep characteristics in both these stages included increased sleep onset latency, increased wake after sleep onset, and reduced sleep efficiency.
Compared with controls, CP was the only clinical group with more arousals. Patients with CP also had more arousals than the CHR-P group, and the number of arousals was significantly affected by medication.
The findings indicate the effects of antipsychotic medications on sleep should be closely monitored, especially in CP, the investigators write.
They add that clinicians should consider medication adjustments, such as decreased doses or switches to another compound.
“Robust” Spindle Results
As for spindle parameters, pooled cases showed significantly decreased spindle density (SMD, -1.06), spindle amplitude (SMD, −1.08), and spindle duration (SMD, −1.21) compared with controls. Stage-specific comparisons revealed these deficits were present in both EP and CP relative to controls.
Ferrarelli noted the results for spindle abnormalities were among “the most robust,” and show that these abnormalities “tend to get worse over the course of the illness.”
The spindle data are “a lot more informative” than that provided by other sleep parameters “in the sense they can yield what could be wrong, where it could be, and potentially what you can do about it,” said Ferrarelli.
“This might be an objective measure that could be used to identify individuals who have a psychosis disorder, monitor progression of illness, and for prognostic reasons,” he added.
He noted that spindles may also represent a promising target for treatment interventions, and added that non-invasive transcranial magnetic stimulation has shown promise in restoring sleep oscillations, including spindles.
Another way to evoke target-brain activity may be through auditory tones — with a patient listening to a particular sound through headphones while asleep, Ferrarelli said.
Reaffirms Previous Data
Commenting for Medscape Medical News, Jeffrey A. Lieberman, MD, professor and chair in psychiatry at Columbia University, New York City, and a past president of the American Psychiatric Association, noted that the review “just reaffirms what has been reported by individual studies for decades.”
That so many at-risk study subjects had a sleep abnormality is not surprising, said Lieberman, who was not involved with the current research.
“How many individuals in late adolescence or early adulthood have sleep problems?” he asked. “I would venture to say it’s probably a lot. So the question is: how distinctive is this from what occurs in people who don’t develop the illness?”
The aim of sleep research in the area of schizophrenia has long been to disentangle the effects of medication and environmental factors from the disease and to be able to treat patients to normalize their sleep, said Lieberman.
“But it’s not clear from these results how one would do that,” he added.
The authors “don’t fundamentally tell us anything about the underlying cause of the illness or the pathophysiology, and they don’t really offer any kind of clear direction for clinical intervention,” he said.
The study was supported by the National Institute of Mental Health. Ferrarelli reported grants from the National Institute of Mental Health during the conduct of the study. Lieberman has reported no relevant financial relationships.
JAMA Psychiatry. Published January 18, 2023. Abstract
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