Summary: Young people with 22q11.2 deletion syndrome show distinct and marked EEG differences in brain activity during sleep, which may influence psychiatric symptoms.
Patterns of brain activity during sleep shed light on the neurobiology behind a genetic condition called 22q11.2 deletion syndrome (22q11.2DS) and could be used as a biomarker to detect the onset of neuropsychiatric disorders in people with 22q11 .2DS.
22q11.2DS is caused by a genetic deletion of approximately 30 genes on chromosome 22 and occurs in 1 in 3000 births. It increases the risk of intellectual disability, autism spectrum disorder (ASD), attention deficit disorder with hyperactivity (ADHD) and epileptic seizures. It is also one of the main biological risk factors for schizophrenia.
However, the biological mechanisms underlying psychiatric symptoms in 22q11.2DS are unclear.
“We have recently shown that the majority of young people with 22q11.2DS have sleep problems, particularly insomnia and sleep fragmentation, which are linked to psychiatric disorders,” says co-author Marianne van den Bree. Principal, Professor of Psychological Medicine at Cardiff University. , UK.
“However, our previous analysis was based on parents’ reports of their children’s sleep quality, and neurophysiology – what happens to brain activity – has not yet been explored.”
The electroencephalogram (EEG) is an established way to measure brain activity during sleep. It measures electrical activity during sleep and exhibits patterns called spindles and slow-wave (SW) oscillations.
These features are hallmarks of non-rapid eye movement (NREM) sleep and are thought to promote memory consolidation and brain development.
“Because the sleep EEG is known to be altered in many neurodevelopmental disorders, the properties and coordination of these alterations can be used as biomarkers of psychiatric dysfunction,” explained lead author Nick Donnelly, master of Clinical Lectures in General Psychiatry for Adults at the University of Bristol, UK.
To explore this in 22q11.2DS, the team recorded sleep EEG overnight in 28 young people aged 6 to 20 with the chromosome deletion and 17 unaffected siblings recruited as part of the Cardiff University Children’s Experiments with Copy Number Variants (ECHO), led by Professor van den Bree. They measured correlations between sleep EEG patterns and psychiatric symptoms, as well as performance on a recall test the next morning.
They found that the group with 22q11.2DS had significant changes in sleep patterns, including a greater proportion of N3 NREM sleep (slow wave sleep) and lower proportions of N1 sleep (the first and lightest stage sleep) and rapid eye movement (REM) sleep. , compared to their siblings.
Those who carried the chromosomal deletion also had increased EEG power for slow wave oscillations and spindles. There was also an increase in the frequency and density of spindle patterns and a stronger coupling between spindle and slow-wave EEG features in the 22q112.DS group.
These changes may reflect alterations in the connections within and between the areas of the brain that generate these oscillations, the cortex and the thalamus.
Participants also participated in a 2D object location task before sleeping, where they had to remember where the corresponding maps were on a screen. They were tested again on the same task in the morning, and the team found that in those with 22q11.2DS, higher spindle and SW amplitudes were associated with lower accuracy.
In contrast, in participants without a chromosome deletion, higher amplitudes were linked to greater accuracy in the morning recall test.
Finally, the team estimated the impact of differences in sleep patterns on psychiatric symptoms in the two groups using a statistical method called mediation.
They calculated the total effect of genotype on psychiatric measures and IQ, the indirect (mediated) effect of EEG measures, and then the proportion of the total effect that may be mediated by EEG patterns.
They found that the effects on anxiety, ADHD and ASD induced by 22q11.2 deletion were partially mediated by sleep EEG differences.
“Our EEG findings together suggest a complex picture of sleep neurophysiology in 22q11.2DS and highlight differences that could serve as potential biomarkers for 22q11.2DS-associated neurodevelopmental syndromes,” concluded co-lead author Matt Jones. , Research Fellow in Neuroscience, University of Bristol, UK.
“Further study will now need to clarify the relationship between psychiatric symptoms, EEG measures of sleep, and neurodevelopment, with a view to identifying markers of brain circuit dysfunction that could inform physicians of patients most at risk and support treatment decisions.
About this sleep and psychiatry research news
Author: Emily Packer
Contact: Emily Packer – eLife
Image: Image is in public domain
Original research: Free access.
“Sleep EEG in young people with 22q11.2 deletion syndrome: a cross-sectional study of slow waves, spindles, and correlations with memory and neurodevelopmental symptoms” by Marianne van den Bree et al. eLife
Sleep EEG in youth with 22q11.2 deletion syndrome: a cross-sectional study of slow waves, spindles, and correlations with memory and neurodevelopmental symptoms
Background: Young people living with 22q11.2 deletion syndrome (22q11.2DS) are at increased risk for schizophrenia, intellectual disability, attention deficit hyperactivity disorder (ADHD), and autism spectrum disorder (ASD). 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 reflects convergent early signatures of neural circuit disruption also evident in associated neurodevelopmental conditions.
Methods : In a cross-sectional design, we recorded a high-density sleep EEG in young people (6-20 years) with 22q11.2DS (n=28) and their unaffected siblings (n=17), quantifying 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 sleep, suppression carriers showed broadband increases in EEG power with increased slow wave and spindle amplitudes, increased frequency and spindle density, and stronger coupling between spindles and waves. slow. Spindle and slow wave amplitudes correlated positively with nocturnal memory in controls, but negatively in 22q11.2DS. Mediation analyzes indicated that the effects of genotype on anxiety, ADHD, and ASD were partially mediated by EEG measures of sleep.
Conclusion : This study provides a detailed description of the neurophysiology of sleep in 22q11.2DS, highlighting alterations in sleep EEG signatures that have previously been linked to neurodevelopment, some of which were associated with psychiatric symptoms. Sleep EEG features may therefore reflect delayed or compromised neurodevelopmental processes in 22q11.2DS, which could inform our understanding of the neurobiology of this condition and be biomarkers of neuropsychiatric disorders.
Funding: This research was funded by a Lilly Innovation Fellowship Award (UB), the National Institute of Mental Health (NIMH 5UO1MH101724; MvdB), a Wellcome Trust Institutional Strategic Support Fund (ISSF) award (MvdB), the Waterloo Foundation (918-1234 ; MvdB), the Baily Thomas Charitable Fund (2315/1; MvdB), MRC Grant for Intellectual Disability and Mental Health: Assessment of Genomic Impact on Neurodevelopment (IMAGINE) (MR/L011166/1; JH, MvdB and MO), MRC Grant for Intellectual Disability and Mental Health: Evaluation of Genomic Impact on Neurodevelopment 2 (IMAGINE-2) (MR/T033045/1; MvdB, JH and MO); Wellcome Trust Strategic Award ‘Defining endophenotypes from integrated neuroscience’ Wellcome Trust (100202/Z/12/Z MO, JH). NAD was supported by a Mental Health Academic Clinical Fellowship from the National Institute for Health Research and MWJ by a Wellcome Trust Senior Fellowship in Basic Biomedical Sciences (202810/Z/16/Z). CE and HAM were supported by doctoral training grants from the Medical Research Council (CBE 1644194, HAM MR/K501347/1). HMM and UB were employed by Eli Lilly & Co during the study; HMM is currently employed by Boehringer Ingelheim Pharma GmbH & Co KG.
Brain activity during sleep differs in young people at genetic risk for psychiatric disorders – Neuroscience News