Multivariate deep phenotyping reveals behavioral correlates of non-restorative sleep in 22q11.2 deletion syndrome

Article Article scientifique Article Multivariate deep phenotyping reveals behavioral correlates of non-restorative sleep in 22q11.2 deletion syndrome eng 2025-02-25 2025-05 author Reich Natacha Laura 0009-0004-1628-4981 941582 author Imparato Andréa 413221 Département de psychiatrie (PSYAT) author Cataldi Jacinthe 896508 author Thillainathan Niveettha 941214 Département de psychiatrie (PSYAT) author Delavari Farnaz 0000-0003-2990-4372 930325 author Schneider Maude 0000-0001-7147-8915 594384 Section de psychologie (PSICO) author Eliez Stéphan 39336 Département de psychiatrie (PSYAT) author Siclari Francesca 514699 author Sandini Corrado 846736 Département de psychiatrie (PSYAT) 116423 10.1016/j.psychres.2025.116423 40023094 0165-1781 https://www.sciencedirect.com/science/article/pii/S0165178125000721 Converging evidence suggests that sleep disturbances can directly contribute to a transdiagnostic combination of behavior and neurocognitive difficulties characterizing most forms of psychopathology. However, it remains unclear how the growing comprehension of sleep neurophysiology should best inform sleep quality assessment in mental health patients. To address this fundamental question, we performed deep multimodal sleep and behavioral phenotyping in 37 individuals at high genetic risk for psychopathology due to 22q11.2 Deletion Syndrome (Mean age:19±8.17, M/F = 22/15) and 34 Healthy Controls (Mean age:17.06±6.87, M/F = 12/22). We implemented a multivariate analysis pipeline informed by the current neurobiological understanding of the behavioral consequences of sleep disruption. We detected multivariate patterns of disrupted sleep architecture consistently influenced by age and diagnosis across recordings and experimental settings. With high-density EEG polysomnography we detected atypical trajectories of Slow-Wave-Activity (SWA) reduction, influenced by age and sleep duration which, according to the Synaptic-Homeostasis-Hypothesis, could reflect combined alterations in neurodevelopmental and synaptic homeostasis mechanisms in 22q11DS. Blunted SWA reduction was linked with EEG markers of residual sleep pressure in morning-vs-evening EEG and with questionnaires estimating subjective somnolence in everyday life, potentially representing a clinically relevant signature of non-restorative sleep. Moreover, blunted SWA decline was linked to a transdiagnostic combination of behavioral difficulties, including negative psychotic symptoms, ADHD symptoms, and neurocognitive impairments in processing speed and inhibitory-control. These findings suggest that systematic screening and management of sleep disturbances could directly improve behavioral outcomes in 22q11DS. They highlight the potential of precision/multivariate phenotyping approaches for characterizing the role of sleep disturbances in developmental psychopathology. ADHD Negative symptoms Obstructive sleep apnea Schizophrenia Synaptic homeostasis Dewey 616.89 Dewey 150 Swiss National Science Foundation The Swiss 22q11DS longitudinal cohort: understanding psychosis proneness through negative symptoms 179404 CH Projects Swiss National Science Foundation Swiss 22q11DS longitudinal cohort: identifying critical developmental time windows for prevention and interventions 212476 CH Projects Swiss National Science Foundation NCCR 'SYNAPSY - The synaptic bases of mental diseases' (phase III) 185897 CH Programmes Swiss National Science Foundation Towards an embodied and ecological understanding of social impairments in neurodevelopmental disorders 174206 CH Careers Swiss National Science Foundation Towards an ecological characterization of affective and sleep co-morbidities in ADHD, through temporal network analysis 209096 CH Careers 60 Département de psychiatrie 225 108 Section de psychologie 71 false 1302 Unité de psychologie clinique des situations de handicap 421 Laboratoire d'imagerie et de psychopathologie développementale 693 1284 NCCR Synapsy Psychiatry research 347 5ee030e6-7be3-4256-b0c2-a4198abf3927 Article (Published version) Public 1-s2.0-S0165178125000721-main.pdf 4447619 application/pdf CC BY-4.0 f3a778175d738d20bf03ceac4d8e26fa294f1d54c3f189c2cd744bdea8208392 e54e4486-b23e-4e3a-992c-7dd7360bda80 Supplemental data Public 1-s2.0-S0165178125000721-mmc1.docx 3346026 application/vnd.openxmlformats-officedocument.wordprocessingml.document c1e7f43912cdd09b1218c11cffc7a8f5be8b0b4adc5ac369317396f01179e359 openAccess Faculté de médecine / Section de médecine clinique / Département de psychiatrie Faculté de psychologie et des sciences de l'éducation / Section de psychologie

Title	Published in	Year	Views	Downloads

Multivariate deep phenotyping reveals behavioral correlates of non-restorative sleep in 22q11.2 deletion syndrome	Psychiatry research	2025	10	4
The neural correlates of dreaming	Nature Neuroscience	2017	588	6

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Siclari, Francesca