This document summarizes a study investigating sleep problems in children and adolescents with 22q11.2 deletion syndrome (22q11.2 DS). The study found higher rates of reported sleep problems in individuals with 22q11.2 DS compared to unaffected siblings. Certain sleep factors, such as tiredness, were associated with specific ADHD subtypes in 22q11.2 DS individuals. The study aims to further examine sleep in this population using actigraphy and polysomnography to better understand sleep phenotypes and implications for psychiatric disorders.

1. Sleep problems in children and
adolescents with 22q11.2 deletion
syndrome
Hayley Moulding
Early Career Neuroscientist Day GW4
Supervised by:
Prof. Marianne van den Bree
Prof. Jeremy Hall
Prof. Sir. Michael Owen

2. The ECHO Study
•Experiences of Children with cOpy number
variants
• Recruits children and adults with CNVs posing a high risk of
developing schizophrenia
• Undertake detailed psychiatric and phenotypic assessments
• Ongoing neuroimaging study (MEG and MRI)
• Pilot sleep study (Actigraphy and EEG assessment)
•One of the largest samples of 22q11.2 DS
children

3. Copy Number Variants
• Copy number variants (CNVs) are segments of DNA, one
kilobase or larger present at a variable copy number
• Sections of DNA (or entire chromosomes) can be deleted
or duplicated
• There are many conditions caused by CNVs
• Down’s syndrome
• Many CNVs are associated with not only physical
health problems, but with mental health disorders

4. 22q11.2 deletion syndrome
• A hemizygous deletion, 97% of
deletions are ~3 Megabases (Mb),
with ~3% having a 1.5 Mb deletion
• Affects 1 in 2500- 4000 live births
(could be more1)
• Multiple and varied physical
symptoms:
• Cleft palate, heart defects,
respiratory defects, immune
dysfunction, etc.
1Wapner, R.J. 2015

5. Psychiatric Phenotype
•Increased risk for the development of schizophrenia
• ~25% of 22q11.2 DS adults develop schizophrenia
compared to ~1% of the general population
•Moderate learning disability
•ADHD
• Hyperactive, inattentive, combined subtypes
•Autism spectrum disorders (ASD)
•Anxiety disorders
•Epilepsy

6. Sleep
• A state of altered consciousness
• Sleep is maintained by:
i. Circadian rhythms – sleep/wake cycle
ii. Homeostatic regulation
• Changes in sleep and circadian rhythms can cause irreparable
physical and psychiatric problems
• If predisposed to psychiatric problems what are the implications
of sleep problems1?
1 Yoo, S.S. 2007

7. Neurodevelopmental disorders
and sleep disturbance
• 22q11.2 DS individuals are affected by many
neurodevelopmental problems
• Sleep problems implicated in ADHD
• Restless sleep1, increased sleep latency onset2, insomnias3 and hypersomnia4
• Sleep-disordered breathing5
• Autistic spectrum disorders show increased rates of sleep problems6
• 50-80% children; cognitive ability makes no difference to prevalence
• Insomnias, sleep disordered breathing, parasomnias and sleep-related
movement disorders6
1,2,3,4Weiss, M.D. (2015) & Cortese, S. et al. 2009 & Sadeh, A. et al 2006; 1Walters, A.S. et
al. 2000; 5Sedyky, K. et al. 2013; 6Konofal, E. et al. 2010; Reynolds, A.M. et al. 2011

8. Sleep problems in 22q11.2DS
• Parent/carer reports of sleep problems in the Child
and Adolescent Psychiatric Assessment (CAPA)
Questionnaire
• Factors:
1) Tired-related; tiredness, fatigability and
hypersomnia
2) Insomnia/terror; initial, middle and early and
night terrors
3) Nightmares/inadequately rested

9. Higher rates of reported-sleep problems in 22q
0
10
20
30
40
50
60
70
22q11.2 DS Unaffected siblings
%individualsreportsleepproblems
***
(p,<0.0001)(n, 124) (n, 102)

10. 22q11.2DS-ADHD subtype matters
for sleep
• 22q individuals with a tired-factor related sleep problem (n=124) showed a borderline
significant association with ADHD outcome (OR, 1.63 95%CI, 0.967-2.76 p, 0.067)
• Tired-factor was significantly associated with an inattentive (n=104) subtype outcome
(OR, 2.09 95%CI, 1.15-3.81 p, 0.016)
• Insomnia/terror-factor showed a non-robust, borderline trend of a significant
association (n=88) with a combined outcome (OR, 1.91 95%CI, 0.640-2.85 p, 0.072)
• There were no associations between sleep factors and a hyperactive subtype
• ADHD subtypes have different sleep phenotypes?
Hyperactive-
impulsivity
Combined
Inattentive

11. Future Work
•Actiwatches – actigraphy data
•EEG – polysomnography
•Longitudinal assessment
•Other higher-SCZ risk CNVs

12. Acknowledgements
Supervisors:
Professor Marianne van den Bree
Professor Jeremy Hall
Professor Sir. Michael Owen
Sophie Andrews
Samuel Chawner
Adam Cunningham
Aimee Davies
Jo Doherty
Ffion Evans
Bethan Hughes
Hayley Moss
Maria Niarchou
Rachael Stickland

13. P-value 95% CI OR
Proband 0.0001 3.69-46.0 13.0
Age 0.304 0.769-1.09 0.914
Gender 0.099 0.215-1.14 0.495
Tiresome factor 0.011 1.12-2.37 1.63
Insomnias-Restless factor 0.419 0.494-1.34 0.814
Parasomnia factor 0.896 0.666-1.59 1.03
P-value 95% CI OR
Proband 0.184 0.462-55.1 5.05
Age 0.804 0.649-1.40 0.953
Gender 0.673 0.0981-1.40 0.663
Tiresome factor 0.571 0.454-4.19 1.38
Insomnias-Restless factor 0.02 1.14-4.80 2.34
Parasomnia factor 0.416 0.191-1.98 0.615
P-value 95% CI OR
Proband 0.044 1.04-15.5 4.01
Age 0.027 0.586-0.968 0.753
Gender 0.165 0.148-1.38 0.453
Tiresome factor 0.520 0.724-1.90 1.17
Insomnias-Restless factor 0.025 1.06-2.48 1.62
Parasomnia factor 0.815 0.668-1.67 1.06
ADHD Inattentive subtype
(n=202)
ADHD Hyperactive subtype
(n=172)
ADHD Combined subtype
(n=186)