Sleep disturbance as a transdiagnostic marker of psychiatric risk in children with neurodevelopmental risk genetic conditions

Abstract Children with rare neurodevelopmental genetic conditions (ND-GCs) are at high risk for a range of neuropsychiatric conditions. Sleep symptomatology may represent a transdiagnostic risk indicator within this patient group. Here we present data from 629 children with ND-GCs, recruited via the United Kingdom’s National Health Service medical genetic clinics. Sibling controls (183) were also invited to take part. Detailed assessments were conducted to characterise the sleep phenotype of children with ND-GCs in comparison to controls. Latent class analysis was conducted to derive subgroups of children with an ND-GC based on sleep symptomatology. Assessment of cognition and psychopathology allowed investigation of whether the sleep phenotypic subgroup was associated with neuropsychiatric outcomes. We found that children with an ND-GC, when compared to control siblings, were at elevated risk of insomnia (ND-GC = 41% vs Controls = 17%, p < 0.001) and of experiencing at least one sleep symptom (ND-GC = 66% vs Controls = 39%, p < 0.001). On average, insomnia was found to have an early onset (2.8 years) in children with an ND-GC and to impact across multiple contexts. Children in subgroups linked to high sleep symptomatology were also at high risk of psychiatric outcomes (OR ranging from 2.0 to 21.5 depending on psychiatric condition). Our findings demonstrate that children with high genetic vulnerability for neurodevelopmental outcomes exhibit high rates of insomnia and sleep symptomatology. Sleep disruption has wide-ranging impacts on psychosocial function, and indexes those children at greater neuropsychiatric risk. Insomnia was found to onset in early childhood, highlighting the potential for early intervention strategies for psychiatric risk informed by sleep profile