NREM sleep signatures of memory disruption and psychiatric symptoms in young people with 22q11.2 deletion syndrome

Background Young 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. Methods We 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. Results 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 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. Conclusions This 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.