BackgroundYoung people with 22q11.2 deletion syndrome (22q11.2DS) are at high risk for neurodevelopmental disorders. Sleep problems may play a role in this risk but their prevalence, nature and links to psychopathology and cognitive function remain undescribed in this population.MethodSleep problems, psychopathology, developmental coordination and cognitive function were assessed in 140 young people with 22q11.2DS (mean age = 10.1, s.d. = 2.46) and 65 unaffected sibling controls (mean age = 10.8, s.d.SD = 2.26). Primary carers completed questionnaires screening for the children's developmental coordination and autism spectrum disorder.ResultsSleep problems were identified in 60% of young people with 22q11.2DS compared to 23% of sibling controls (OR 5.00, p < 0.001). Two patterns best-described sleep problems in 22q11.2DS: restless sleep and insomnia. Restless sleep was linked to increased ADHD symptoms (OR 1.16, p < 0.001) and impaired executive function (OR 0.975, p = 0.013). Both patterns were associated with elevated symptoms of anxiety disorder (restless sleep: OR 1.10, p = 0.006 and insomnia: OR 1.07, p = 0.045) and developmental coordination disorder (OR 0.968, p = 0.0023, and OR 0.955, p = 0.009). The insomnia pattern was also linked to elevated conduct disorder symptoms (OR 1.53, p = 0.020).ConclusionsClinicians and carers should be aware that sleep problems are common in 22q11.2DS and index psychiatric risk, cognitive deficits and motor coordination problems. Future studies should explore the physiology of sleep and the links with the neurodevelopment in these young people.

BackgroundYoung people with 22q11.2 Deletion Syndrome (22q11.2DS) are at increased risk of schizophrenia, intellectual disability, Attention-Deficit Hyperactivity Disorder (ADHD) and autism spectrum disorder. 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 may reflect convergent, early signatures of neural circuit disruption also evident in associated neurodevelopmental conditions.MethodsWe recorded high-density sleep EEG in young people (6-20 years) with 22q11.2DS (n=28) and their unaffected siblings (n=17), quantifying the 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.Results22q11.2DS 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 NREM sleep, deletion carriers showed increased power in slow delta and sigma oscillations, increased slow-wave and spindle amplitudes, and altered 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 increased slow-wave amplitude in 22q11.2DS was statistically mediated via ADHD symptoms.ConclusionsThis first study of sleep EEG in 22q11.2DS highlights several alterations in EEG signatures of NREM sleep, some of which were associated with ADHD symptoms. ADHD symptoms have previously been associated with incident psychotic symptoms in 22q11.2DS; our findings may therefore reflect delayed or compromised neurodevelopmental processes which precede, and may be biomarkers for, psychotic disorders.