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In common with these conditions, 22q11.2DS is also associated with sleep problems. We investigated whether abnormal sleep or sleep-dependent network activity in 22q11.2DS reflects convergent, early signatures of neural circuit disruption also evident in associated neurodevelopmental conditions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs2\">\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>In a cross-sectional design, we recorded high-density sleep EEG in young people (6\u201320 years) with 22q11.2DS (n=28) and their unaffected siblings (n=17), quantifying associations between sleep architecture, EEG oscillations (spindles and slow waves) and psychiatric symptoms. We also measured performance on a memory task before and after sleep.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs3\">\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>22q11.2DS was associated with significant alterations in sleep architecture, including a greater proportion of N3 sleep and lower proportions of N1 and REM sleep than in siblings. During sleep, deletion carriers showed broadband increases in EEG power with increased slow-wave and spindle amplitudes, increased spindle frequency and density, and stronger coupling between spindles and slow-waves. Spindle and slow-wave amplitudes correlated positively with overnight memory in controls, but negatively in 22q11.2DS. Mediation analyses indicated that genotype effects on anxiety, ADHD and ASD were partially mediated by sleep EEG measures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs4\">\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>This study provides a detailed description of sleep neurophysiology in 22q11.2DS, highlighting alterations in EEG signatures of sleep which have been previously linked to neurodevelopment, some of which were associated with psychiatric symptoms. Sleep EEG features may therefore reflect delayed or compromised neurodevelopmental processes in 22q11.2DS, which could inform our understanding of the neurobiology of this condition and be biomarkers for neuropsychiatric disorders.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs5\">\n                    <jats:title>Funding:<\/jats:title>\n                    <jats:p>This research was funded by a Lilly Innovation Fellowship Award (UB), the National Institute of Mental Health (NIMH 5UO1MH101724; MvdB), a Wellcome Trust Institutional Strategic Support Fund (ISSF) award (MvdB), the Waterloo Foundation (918-1234; MvdB), the Baily Thomas Charitable Fund (2315\/1; MvdB), MRC grant Intellectual Disability and Mental Health: Assessing Genomic Impact on Neurodevelopment (IMAGINE) (MR\/L011166\/1; JH, MvdB and MO), MRC grant Intellectual Disability and Mental Health: Assessing Genomic Impact on Neurodevelopment 2 (IMAGINE-2) (MR\/T033045\/1; MvdB, JH and MO); Wellcome Trust Strategic Award \u2018Defining Endophenotypes From Integrated Neurosciences\u2019 Wellcome Trust (100202\/Z\/12\/Z MO, JH). NAD was supported by a National Institute for Health Research Academic Clinical Fellowship in Mental Health and MWJ by a Wellcome Trust Senior Research Fellowship in Basic Biomedical Science (202810\/Z\/16\/Z). CE and HAM were supported by Medical Research Council Doctoral Training Grants (C.B.E. 1644194, H.A.M MR\/K501347\/1). HMM and UB were employed by Eli Lilly &amp; Co during the study; HMM is currently an employee of Boehringer Ingelheim Pharma GmbH &amp; Co KG. The views and opinions expressed are those of the author(s), and not necessarily those of the NHS, the NIHR or the Department of Health funders.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.7554\/elife.75482","type":"journal-article","created":{"date-parts":[[2022,8,15]],"date-time":"2022-08-15T05:15:12Z","timestamp":1660540512000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.75482","source":"Crossref","is-referenced-by-count":28,"title":["Sleep EEG in young people with 22q11.2 deletion syndrome: A cross-sectional study of slow-waves, spindles and correlations with memory and neurodevelopmental symptoms"],"prefix":"10.7554","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2234-8545","authenticated-orcid":true,"given":"Nicholas A","family":"Donnelly","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0524sp257","id-type":"ROR","asserted-by":"publisher"}],"name":"Centre for Academic Mental Health, University of Bristol","place":["Bristol, United Kingdom"]},{"id":[{"id":"https:\/\/ror.org\/0379k6g72","id-type":"ROR","asserted-by":"publisher"}],"name":"Avon and Wiltshire Partnership NHS Mental Health Trust","place":["Avon, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2213-8989","authenticated-orcid":true,"given":"Ullrich","family":"Bartsch","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0524sp257","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Physiology, Pharmacology and Neuroscience, University of Bristol","place":["Bristol, United Kingdom"]},{"id":[{"id":"https:\/\/ror.org\/01qat3289","id-type":"ROR","asserted-by":"publisher"}],"name":"Translational Neuroscience, Eli Lilly","place":["Windlesham, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayley A","family":"Moulding","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03kk7td41","id-type":"ROR","asserted-by":"publisher"}],"name":"Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Cardiff University","place":["Cardiff, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6739-1999","authenticated-orcid":true,"given":"Christopher","family":"Eaton","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03kk7td41","id-type":"ROR","asserted-by":"publisher"}],"name":"Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Cardiff University","place":["Cardiff, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugh","family":"Marston","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01qat3289","id-type":"ROR","asserted-by":"publisher"}],"name":"Translational Neuroscience, Eli Lilly","place":["Windlesham, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica H","family":"Hall","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03kk7td41","id-type":"ROR","asserted-by":"publisher"}],"name":"Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Cardiff University","place":["Cardiff, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Hall","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03kk7td41","id-type":"ROR","asserted-by":"publisher"}],"name":"Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Cardiff University","place":["Cardiff, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J","family":"Owen","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03kk7td41","id-type":"ROR","asserted-by":"publisher"}],"name":"Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Cardiff University","place":["Cardiff, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne BM","family":"van den Bree","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03kk7td41","id-type":"ROR","asserted-by":"publisher"}],"name":"Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Cardiff University","place":["Cardiff, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matt W","family":"Jones","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0524sp257","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Bristol","place":["Bristol, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2022,8,30]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"746","DOI":"10.1038\/s41583-019-0223-4","article-title":"Oscillating circuitries in the sleeping brain","volume":"20","author":"Adamantidis","year":"2019","journal-title":"Nature Reviews. 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