학술논문
A spectrum of altered non-rapid eye movement sleep in schizophrenia.
Document Type
Author
Kozhemiako N; Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School; Boston, USA.; Jiang C; The Affiliated Wuxi Mental Health Center of Nanjing Medical University; Wuxi, China.; Sun Y; The Affiliated Wuxi Mental Health Center of Nanjing Medical University; Wuxi, China.; Guo Z; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard; Boston, USA.; Chapman S; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard; Boston, USA.; Gai G; The Affiliated Wuxi Mental Health Center of Nanjing Medical University; Wuxi, China.; Wang Z; The Affiliated Wuxi Mental Health Center of Nanjing Medical University; Wuxi, China.; Zhou L; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard; Boston, USA.; Li S; Department of Psychiatry, McLean Hospital, Harvard Medical School; Boston, USA.; Law RG; Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School; Boston, USA.; Wang LA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard; Boston, USA.; Mylonas D; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School; Boston, USA.; Shen L; Bio-X Institutes, Shanghai Jiao Tong University; Shanghai China.; Murphy M; Department of Psychiatry, McLean Hospital, Harvard Medical School; Boston, USA.; Qin S; Bio-X Institutes, Shanghai Jiao Tong University; Shanghai China.; Zhu W; The Affiliated Wuxi Mental Health Center of Nanjing Medical University; Wuxi, China.; Zhou Z; The Affiliated Wuxi Mental Health Center of Nanjing Medical University; Wuxi, China.; Stickgold R; Beth Israel Deaconess Medical Center; Boston, USA.; Department of Psychiatry, Harvard Medical School; Boston, USA.; Huang H; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard; Boston, USA.; ATGU, MGH, Harvard Medical School; Boston, USA.; Tan S; Huilong Guan Hospital, Beijing University; Beijing China.; Manoach DS; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School; Boston, USA.; Wang J; The Affiliated Wuxi Mental Health Center of Nanjing Medical University; Wuxi, China.; Hall MH; Department of Psychiatry, McLean Hospital, Harvard Medical School; Boston, USA.; Pan JQ; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard; Boston, USA.; Purcell SM; Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School; Boston, USA.; Department of Psychiatry, Harvard Medical School; Boston, USA.
Source
Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE
Subject
Language
English
Abstract
Background: Multiple facets of sleep neurophysiology, including electroencephalography (EEG) metrics such as non-rapid eye movement (NREM) spindles and slow oscillations (SO), are altered in individuals with schizophrenia (SCZ). However, beyond group-level analyses which treat all patients as a unitary set, the extent to which NREM deficits vary among patients is unclear, as are their relationships to other sources of heterogeneity including clinical factors, illness duration and ageing, cognitive profiles and medication regimens. Using newly collected high density sleep EEG data on 103 individuals with SCZ and 68 controls, we first sought to replicate our previously reported (Kozhemiako et. al, 2022) group-level mean differences between patients and controls (original N =130). Then in the combined sample ( N =301 including 175 patients), we characterized patient-to-patient variability in NREM neurophysiology.
Results: We replicated all group-level mean differences and confirmed the high accuracy of our predictive model (Area Under the ROC Curve, AUC = 0.93 for diagnosis). Compared to controls, patients showed significantly increased between-individual variability across many (26%) sleep metrics, with patterns only partially recapitulating those for group-level mean differences. Although multiple clinical and cognitive factors were associated with NREM metrics including spindle density, collectively they did not account for much of the general increase in patient-to-patient variability. Medication regimen was a greater (albeit still partial) contributor to variability, although original group mean differences persisted after controlling for medications. Some sleep metrics including fast spindle density showed exaggerated age-related effects in SCZ, and patients exhibited older predicted biological ages based on an independent model of ageing and the sleep EEG.
Conclusion: We demonstrated robust and replicable alterations in sleep neurophysiology in individuals with SCZ and highlighted distinct patterns of effects contrasting between-group means versus within-group variances. We further documented and controlled for a major effect of medication use, and pointed to greater age-related change in NREM sleep in patients. That increased NREM heterogeneity was not explained by standard clinical or cognitive patient assessments suggests the sleep EEG provides novel, nonredundant information to support the goals of personalized medicine. Collectively, our results point to a spectrum of NREM sleep deficits among SCZ patients that can be measured objectively and at scale, and that may offer a unique window on the etiological and genetic diversity that underlies SCZ risk, treatment response and prognosis.
Results: We replicated all group-level mean differences and confirmed the high accuracy of our predictive model (Area Under the ROC Curve, AUC = 0.93 for diagnosis). Compared to controls, patients showed significantly increased between-individual variability across many (26%) sleep metrics, with patterns only partially recapitulating those for group-level mean differences. Although multiple clinical and cognitive factors were associated with NREM metrics including spindle density, collectively they did not account for much of the general increase in patient-to-patient variability. Medication regimen was a greater (albeit still partial) contributor to variability, although original group mean differences persisted after controlling for medications. Some sleep metrics including fast spindle density showed exaggerated age-related effects in SCZ, and patients exhibited older predicted biological ages based on an independent model of ageing and the sleep EEG.
Conclusion: We demonstrated robust and replicable alterations in sleep neurophysiology in individuals with SCZ and highlighted distinct patterns of effects contrasting between-group means versus within-group variances. We further documented and controlled for a major effect of medication use, and pointed to greater age-related change in NREM sleep in patients. That increased NREM heterogeneity was not explained by standard clinical or cognitive patient assessments suggests the sleep EEG provides novel, nonredundant information to support the goals of personalized medicine. Collectively, our results point to a spectrum of NREM sleep deficits among SCZ patients that can be measured objectively and at scale, and that may offer a unique window on the etiological and genetic diversity that underlies SCZ risk, treatment response and prognosis.