Introduction Disturbed sleep is a common feature of psychotic disorders that is also present in the clinical high risk (CHR) state. Evidence suggests a potential role of sleep disturbance in symptom progression, yet the interrelationship between sleep and CHR symptoms remains to be determined. To address this knowledge gap, we examined the association between disturbed sleep and CHR symptoms over time. Methods Data were obtained from the North American Prodrome Longitudinal Study (NAPLS)-3 consortium, including 688 CHR individuals and 94 controls (mean age 18.25, 46% female) for whom sleep was tracked prospectively for 8 months. We used Cox regression analyses to investigate whether sleep disturbances predicted conversion to psychosis up to >2 years later. With regressions and cross-lagged panel models, we analyzed longitudinal and bidirectional associations between sleep (the Pittsburgh Sleep Quality Index in conjunction with additional sleep items) and CHR symptoms. We also investigated the independent contribution of individual sleep characteristics on CHR symptom domains separately and explored whether cognitive impairments, stress, depression, and psychotropic medication affected the associations. Results Disturbed sleep at baseline did not predict conversion to psychosis. However, sleep disturbance was strongly correlated with heightened CHR symptoms over time. Depression accounted for half of the association between sleep and symptoms. Importantly, sleep was a significant predictor of CHR symptoms but not vice versa, although bidirectional effect sizes were similar. Discussion The critical role of sleep disturbance in CHR symptom changes suggests that sleep may be a promising intervention target to moderate outcome in the CHR state.

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ImportanceReproductive system and mental health disorders are commonly comorbid in women. Although the causes of this overlap remain elusive, evidence suggests potential shared environmental and genetic factors associated with risk.ObjectiveTo investigate the comorbidity between psychiatric and reproductive system disorders, both as broad diagnostic categories and among specific pairs of diagnoses.Data SourcePubMed.Study SelectionObservational studies published between January 1980 and December 2019 assessing prevalence of psychiatric disorders in women with reproductive system disorders and prevalence of reproductive system disorders in women with psychiatric disorders were included. The study did not include psychiatric and reproductive disorders triggered by life events (eg, trauma, infection, surgery) to address potential confounding.Data Extraction and SynthesisA search yielded 1197 records, of which 50 met the inclusion criteria for the qualitative and 31 for the quantitative synthesis in our study. A random-effects model was used for data synthesis and Egger test and I2 to assess study bias and heterogeneity. Data were analyzed from January to December 2022. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline.Main Outcomes and MeasuresPsychiatric and reproductive system disorders.ResultsA total of 1197 records were identified, of which 50 met the inclusion criteria for qualitative and 31 for quantitative synthesis. Diagnosis of a reproductive system disorder was associated with a 2- to 3-fold increased odds of having a psychiatric disorder (lower bound odds ratio [OR], 2.00; 95% CI, 1.41-2.83; upper bound OR; 2.88; 95% CI, 2.21-3.76). The analysis focused on specific diagnoses described in the literature and found that polycystic ovary syndrome was associated with increased odds of depression (population-based studies OR, 1.71; 95% CI, 1.19-2.45; clinical studies OR, 2.58; 95% CI, 1.57-4.23) and anxiety (population-based studies OR, 1.69; 95% CI, 1.36-2.10; clinical studies OR, 2.85; 95% CI, 1.98-4.09). Chronic pelvic pain was also associated with both depression (OR, 3.91; 95% CI, 1.81-8.46) and anxiety (OR, 2.33; 95% CI, 1.33-4.08). Few studies investigated risk of other reproductive system disorders in women with psychiatric disorders, or reverse associations (risk of reproductive system disorder among women with a psychiatric diagnosis).Conclusions and RelevanceIn this systematic review and meta-analysis, a high rate of reported co-occurrence between psychiatric and reproductive disorders overall was observed. However, data for many disorder pairs were limited. The available literature focused overwhelmingly on affective disorders in polycystic ovary syndrome, overlooking a substantial portion of disease overlap. As such, the associations between the majority of mental health outcomes and conditions of the female reproductive system are largely unknown.

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The following text is now added to the beginning of the fourth paragraph of the 'Statistical analysis' subsection of the Methods section: "A normalization factor can be added to account for the uncertainty in the symptom onset dates of the index cases. Assuming a uniform distribution, the likelihood would only differ by a multiplicative constant and give the same estimates. " Also, the time frame in the final sentence of that paragraph ("from day 1 to 7") was incorrect. The correct time frame is "from days 5, 8 and 11. " Finally, Fig. 1c and Extended Data Fig. 1 have been replaced accordingly, and the legend to Extended Data Fig. 1 ("to start from 1 days (top left) to 7 days (bottom right) before symptom onset") is now rephrased ("to start from 5 days (top), 8 days (middle) and 11 days (bottom) before symptom onset") to match the revised figure. The errors have been corrected in the HTML and PDF versions of the article. The original code has also been replaced with updated code in Supplementary Software 1.