Interindividual Sleep Variability Across the Psychosis Spectrum: A Systematic Review and Meta-Analysis.

Importance: Sleep disturbances are common across the psychosis spectrum and may precede overt core clinical symptoms. Most studies focus on mean differences and overlook interindividual variability, which can be informative for stratified care. Objective: To quantify interindividual variability in actigraphy sleep measures across psychosis stages among individuals at clinical high risk for psychosis (CHR-P) and those with schizophrenia spectrum disorders (SSDs) compared with healthy control participants. Data Sources: The PubMed, Embase, MEDLINE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, EU Clinical Trials Register, World Health Organization International Clinical Trials Registry Platform, and OpenGrey databases were searched for studies published from inception to April 29, 2024. An updated search was performed to identify studies published between April 30, 2024, and April 25, 2026. Study Selection: Case-control studies using wrist actigraphy in participants at CHR-P or with SSDs compared with healthy control participants were selected. Data Extraction and Synthesis: This systematic review and meta-analysis was preregistered with the Center for Open Science and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Data were independently extracted under PRISMA standards. Two reviewers independently applied the inclusion criteria. Main Outcomes and Measures: The primary outcome was the natural logarithm of the variability ratio (lnVR) for total sleep time (TST). Secondary outcomes were the lnVR and the natural logarithm of the coefficient of variation ratio (lnCVR) for all actigraphy sleep parameters, including time in bed (TIB), sleep latency, wake after sleep onset (WASO), sleep efficiency, and number of awakenings. Variability metrics (lnVR and lnCVR) were pooled using random-effects models. Heterogeneity was assessed with Q, I2, and τ2 values and 95% CIs. Univariable mixed-effects meta-regression analysis tested antipsychotic use, with age and sex as moderators of the primary outcome. Each key result was tested against a panel of sensitivity analyses. Results: Of the 19 studies that met criteria, 18 entered the quantitative synthesis (1 study reported outcomes as medians and was excluded). Eighteen studies (n = 1358), including 202 individuals at CHR-P (mean [SD] age, 20.7 [2.8] years; 104 female [51.4%]), 574 individuals with SSDs (mean [SD] age, 37.7 [10.2] years; 363 female [63.2%]), and 582 healthy control participants (mean [SD] age, 31.5 [8.6] years; 311 male [53.4%]), were meta-analyzed. Participants at CHR-P had greater variability in TIB (lnVR, 0.29 [95% CI, 0.04-0.54] minutes; I2 = 0%; P = .02), WASO (0.45 [95% CI, 0.07-0.83] minutes; I2 = 83%; P = .02), and sleep efficiency (0.35% [95% CI, 0.06%-0.64%]; I2 = 72%; P = .02). Participants with SSDs had greater variability in TST (0.46 [95% CI, 0.28-0.64] minutes; I2 = 70%; P < .001), TIB (0.38 [95% CI, 0.19-0.56] minutes; I2 = 0%; P < .001), WASO (0.52 [95% CI, 0.15-0.89] minutes; I2 = 88%; P = .006), and sleep efficiency (0.27% [95% CI, 0.04%-0.50%]; I2 = 71%; P = .02). Moderator effects were nonsignificant. Conclusions and Relevance: In this systematic review and meta-analysis of 18 case-control studies, distinct digital phenotypes of sleep variability were identified among individuals across the psychosis spectrum compared with healthy control participants. These findings support further investigations of sleep as a candidate biomarker to inform stratified care in psychosis.