Abnormal sleep physiology in children with 15q11.2-13.1 duplication (Dup15q) syndrome.

Autor: Saravanapandian V; Center for Autism Research and Treatment, Semel Institute for Neuroscience, University of California, Los Angeles, Los Angeles, CA, 90024, USA. vidyasaravanapandian@gmail.com.; Neuroscience Interdepartmental Ph.D. Program, University of California, Los Angeles, Los Angeles, CA, 90095, USA. vidyasaravanapandian@gmail.com., Nadkarni D; Division of Pediatric Epilepsy, Department of Pediatric Neurology, Children's Hospital Medical Center of Akron, Akron, OH, 44308, USA., Hsu SH; Swartz Center for Computational Neuroscience, UC San Diego, La Jolla, USA., Hussain SA; Division of Pediatric Neurology, David Geffen School of Medicine, UCLA Mattel Children's Hospital, Los Angeles, CA, USA., Maski K; Department of Neurology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA., Golshani P; Department of Neurology and Semel Institute for Neuroscience, David Geffen School of Medicine, 710 Westwood Plaza, Los Angeles, CA, 90095, USA.; West Los Angeles VA Medical Center, 11301 Wilshire Blvd, Los Angeles, CA, 90073, USA., Colwell CS; Department of Psychiatry and Biobehavioral Sciences, Semel Institute, University of California, Los Angeles, Los Angeles, CA, 90095, USA., Balasubramanian S; Microsoft, Sunnyvale, CA, 94089, USA., Dixon A; Undergraduate Interdepartmental Program for Neuroscience, University of California, Los Angeles, Los Angeles, CA, 90095, USA., Geschwind DH; Center for Autism Research and Treatment, Semel Institute for Neuroscience, University of California, Los Angeles, Los Angeles, CA, 90024, USA., Jeste SS; Children's Hospital Los Angeles, Los Angeles, CA, USA.
Jazyk: angličtina
Zdroj: Molecular autism [Mol Autism] 2021 Aug 03; Vol. 12 (1), pp. 54. Date of Electronic Publication: 2021 Aug 03.
DOI: 10.1186/s13229-021-00460-8
Abstrakt: Background: Sleep disturbances in autism spectrum disorder (ASD) represent a common and vexing comorbidity. Clinical heterogeneity amongst these warrants studies of the mechanisms associated with specific genetic etiologies. Duplications of 15q11.2-13.1 (Dup15q syndrome) are highly penetrant for neurodevelopmental disorders (NDDs) such as intellectual disability and ASD, as well as sleep disturbances. Genes in the 15q region, particularly UBE3A and a cluster of GABA A receptor genes, are critical for neural development, synaptic protein synthesis and degradation, and inhibitory neurotransmission. During awake electroencephalography (EEG), children with Dup15q syndrome demonstrate increased beta band oscillations (12-30 Hz) that likely reflect aberrant GABAergic neurotransmission. Healthy sleep rhythms, necessary for robust cognitive development, are also highly dependent on GABAergic neurotransmission. We therefore hypothesized that sleep physiology would be abnormal in children with Dup15q syndrome.
Methods: To test the hypothesis that elevated beta oscillations persist in sleep in Dup15q syndrome and that NREM sleep rhythms would be disrupted, we computed: (1) beta power, (2) spindle density, and (3) percentage of slow-wave sleep (SWS) in overnight sleep EEG recordings from a cohort of children with Dup15q syndrome (n = 15) and compared them to age-matched neurotypical children (n = 12).
Results: Children with Dup15q syndrome showed abnormal sleep physiology with elevated beta power, reduced spindle density, and reduced or absent SWS compared to age-matched neurotypical controls.
Limitations: This study relied on clinical EEG where sleep staging was not available. However, considering that clinical polysomnograms are challenging to collect in this population, the ability to quantify these biomarkers on clinical EEG-routinely ordered for epilepsy monitoring-opens the door for larger-scale studies. While comparable to other human studies in rare genetic disorders, a larger sample would allow for examination of the role of seizure severity, medications, and developmental age that may impact sleep physiology.
Conclusions: We have identified three quantitative EEG biomarkers of sleep disruption in Dup15q syndrome, a genetic condition highly penetrant for ASD. Insights from this study not only promote a greater mechanistic understanding of the pathophysiology defining Dup15q syndrome, but also lay the foundation for studies that investigate the association between sleep and cognition. Abnormal sleep physiology may undermine healthy cognitive development and may serve as a quantifiable and modifiable target for behavioral and pharmacological interventions.
(© 2021. The Author(s).)
Databáze: MEDLINE
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