Copy number variation at the 22q11.2 locus influences prevalence, severity, and psychiatric impact of sleep disturbance

O’Hora, Kathleen; Lin, Amy; Kushan-Wells, Leila; Bearden, Carrie E.

doi:10.1186/s11689-022-09450-0

Cited by 10 publications

(3 citation statements)

References 77 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is possible that this result can be attributed to ADHD symptoms, which are prevalent in both 22qDel and 22qDup carriers (Olsen et al, 2018). In the present cohort and previously studied cohort, there is no difference in prevalence or severity of ADHD symptoms between 22qDel and 22qDup carriers (Lin et al, 2020; O'Hora, Lin, et al, 2022). However, the majority of individuals with ADHD in the 22qDel group meet criteria for the inattentive ADHD subtype, while majority of the 22qDup carriers with ADHD meet criteria for the combined ADHD subtype (Table 2).…”

Section: Discussionsupporting

confidence: 46%

Distinct neurocognitive profiles and clinical phenotypes associated with copy number variation at the 22q11.2 locus

O'Hora,

Kushan‐Wells,

Schleifer

et al. 2023

Autism Research

Self Cite

View full text Add to dashboard Cite

Rare genetic variants that confer large effects on neurodevelopment and behavioral phenotypes can reveal novel gene‐brain‐behavior relationships relevant to autism. Copy number variation at the 22q11.2 locus offer one compelling example, as both the 22q11.2 deletion (22qDel) and duplication (22qDup) confer increased likelihood of autism spectrum disorders (ASD) and cognitive deficits, but only 22qDel confers increased psychosis risk. Here, we used the Penn Computerized Neurocognitive Battery (Penn‐CNB) to characterized neurocognitive profiles of 126 individuals: 55 22qDel carriers (MAge = 19.2 years, 49.1% male), 30 22qDup carriers (MAge = 17.3 years, 53.3% male), and 41 typically developing (TD) subjects (MAge = 17.3 years, 39.0% male). We performed linear mixed models to assess group differences in overall neurocognitive profiles, domain scores, and individual test scores. We found all three groups exhibited distinct overall neurocognitive profiles. 22qDel and 22qDup carriers showed significant accuracy deficits across all domains relative to controls (episodic memory, executive function, complex cognition, social cognition, and sensorimotor speed), with 22qDel carriers exhibiting more severe accuracy deficits, particularly in episodic memory. However, 22qDup carriers generally showed greater slowing than 22qDel carriers. Notably, slower social cognition speed was uniquely associated with increased global psychopathology and poorer psychosocial functioning in 22qDup. Compared to TD, 22q11.2 copy number variants (CNV) carriers failed to show age‐associated improvements in multiple cognitive domains. Exploratory analyses revealed 22q11.2 CNV carriers with ASD exhibited differential neurocognitive profiles, based on 22q11.2 copy number. These results suggest that there are distinct neurocognitive profiles associated with either a loss or gain of genomic material at the 22q11.2 locus.

show abstract

Section: Discussionsupporting

confidence: 46%

Distinct neurocognitive profiles and clinical phenotypes associated with copy number variation at the 22q11.2 locus

O'Hora,

Kushan‐Wells,

Schleifer

et al. 2023

Autism Research

Self Cite

View full text Add to dashboard Cite

show abstract

“…It is possible that this result can be attributed to ADHD symptoms, which are prevalent in both 22qDel and 22qDup carriers (Olsen et al, 2018). However, in the present cohort and previously studied cohort, there is no difference in prevalence or severity of ADHD symptoms between 22qDel and 22qDup carriers (Lin et al, 2020;O'Hora, Lin, Kushan-Wells, & Bearden, 2022;Olsen et al, 2018). One potential future direction to better address this question is to examine trial-by-trial variability in response speed, which is a reliable marker of attention lapses (Chang, Lenartowicz, Hellemann, Uddin, & Bearden, 2022;Leth-Steensen, Elbaz, & Douglas, 2000).…”

Section: Discussionmentioning

confidence: 50%

Distinct Neurocognitive Profiles and Clinical Phenotypes Associated with Copy Number Variation at the 22q11.2 Locus

O’Hora

Kushan-Wells

Hoftman

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

Rare genetic variants that confer large effects on neurodevelopment and behavioral phenotypes can reveal novel gene-brain-behavior relationships relevant to autism. Copy number variation at the 22q11.2 locus offer one compelling example, as both the 22q11.2 deletion (22qDel) and duplication (22qDup) confer increased likelihood of autism spectrum disorders (ASD) and cognitive deficits, but only 22qDel confers increased psychosis risk. Here, we used the Penn Computerized Neurocognitive Battery (Penn-CNB) to characterized neurocognitive profiles of 126 individuals: 55 22qDel carriers (MAge=19.2 years, 49.1% male), 30 22qDup carriers (MAge=17.3 years, 53.3 % male), and 41 typically developing (TD) subjects (MAge=17.3 years, 39.0 % male). We performed linear mixed models to assess group differences in overall neurocognitive profiles, domain scores, and individual test scores. We found all three groups exhibited distinct overall neurocognitive profiles. 22qDel and 22qDup carriers showed significant accuracy deficits across all domains relative to controls (Episodic Memory, Executive Function, Complex Cognition, Social Cognition, and Sensorimotor Speed), with 22qDel carriers exhibiting more severe accuracy deficits, particularly in Episodic Memory. However, 22qDup carriers generally showed greater slowing than 22qDel carriers. Notably, slower social cognition speed was uniquely associated with increased global psychopathology and poorer psychosocial functioning in 22qDup. Compared to TD, 22q11.2 CNV carriers failed to show age-associated improvements in multiple cognitive domains. Exploratory analyses revealed 22q11.2 CNV carriers with ASD exhibited differential neurocognitive profiles, based on 22q11.2 copy number. These results suggest that there are distinct neurocognitive profiles associated with either a loss or gain of genomic material at the 22q11.2 locus.

show abstract

“…However, available evidence indicates that sleep disorders might be over-represented [36]. Subjective complaints of sleep onset delay, agitated sleep, and excessive daytime sleep might be more prevalent in 22q11DS [37][38][39]. Moreover, Obstructive Sleep Apnea (OSA) might affect up to 40% of individuals with 22q11DS, due to a combination of risk factors including retrognathia, hypotonia and velopharyngeal abnormalities [36,[40][41][42].…”

Section: Introductionmentioning

confidence: 99%

Multivariate patterns of disrupted sleep longitudinally predict affective vulnerability to psychosis in 22q11.2 Deletion Syndrome

Reich

Delavari

Schneider

et al. 2023

Preprint

View full text Add to dashboard Cite

22q11.2 deletion syndrome (22q11DS) contributes dramatically increased genetic risk for psychopathology, and in particular schizophrenia. Sleep disorders, including obstructive sleep apnea (OSA), are also highly prevalent, making 22q11DS a unique model to explore their impact on psychosis vulnerability. Still, the contribution of sleep disturbances to psychosis vulnerability remains unclear. We characterized the sleep phenotype of 69 individuals with 22q11DS and 38 healthy controls with actigraphy and sleep questionnaires. Psychiatric symptoms were measured concomitantly with the baseline sleep assessment and at longitudinal follow-up, 3.58±0.85 years later. We used a novel multivariate partial-least-square-correlation (PLSC) approach to identify sleep patterns combining objective and subjective variables, which correlated with psychiatric symptoms. We dissected longitudinal pathways linking sleep disturbances to psychosis, using multi-layer-network-analysis. 22q11DS was characterized by a non-restorative sleep pattern, combining increased daytime fatigue despite longer sleep duration. Non-restorative sleep combined with OSA symptoms correlated with both emotional and psychotic symptoms. Moreover, a sleep pattern evocative of OSA predicted longitudinal worsening of positive and negative symptoms, by accentuating the effects of emotional dysregulation. These results suggest that sleep disturbances could significantly increase psychosis risk, along an affective pathway. If confirmed, this suggests that systematic screening of sleep quality could mitigate psychosis vulnerability in 22q11DS.

show abstract

Copy number variation at the 22q11.2 locus influences prevalence, severity, and psychiatric impact of sleep disturbance

Cited by 10 publications

References 77 publications

Distinct neurocognitive profiles and clinical phenotypes associated with copy number variation at the 22q11.2 locus

Distinct neurocognitive profiles and clinical phenotypes associated with copy number variation at the 22q11.2 locus

Distinct Neurocognitive Profiles and Clinical Phenotypes Associated with Copy Number Variation at the 22q11.2 Locus

Multivariate patterns of disrupted sleep longitudinally predict affective vulnerability to psychosis in 22q11.2 Deletion Syndrome

Contact Info

Product

Resources

About