Young people living with a genetic alteration that increases the risk of psychiatric disorders have markedly different brain activity during sleep, a new study shows that 22q11.2DS is caused by a genetic deletion of around 30 genes on chromosome 22 and It occurs in 1 in 3,000 births. It increases the risk of intellectual disability, autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and epileptic seizures.
It is also one of the biggest biological risk factors for schizophrenia. However, the biological mechanisms underlying the psychiatric symptoms in 22q11.2DS are unclear. “We have recently shown that the majority of young people with 22q11.2DS have sleep problems, in particular insomnia and fragmented sleep, which are related to psychiatric disorders,” says co-senior author Marianne van den Bree, Professor of Psychological Medicine at the University of Cardiff. , UK.
“However, our previous analysis was based on parents’ reports of their children’s sleep quality, and the neurophysiology of what happens to brain activity has not yet been explored.” An established way of measuring brain activity during sleep is an electroencephalogram (EEG).
This measures electrical activity during sleep and shows patterns called spindles and slow wave (SW) oscillations. These features are hallmarks of non-rapid eye movement (NREM) sleep and are thought to aid in memory consolidation and brain development. “Because sleep EEG is known to be altered in many neurodevelopmental disorders, the properties and timing of these alterations can be used as biomarkers for psychiatric dysfunction,” explained senior author Nick Donnelly, clinical professor of general psychiatry at adults at the University of Bristol, UK.
To explore this in 22q11.2DS, the team recorded overnight sleep EEG in 28 young people between the ages of 6 and 20 with the chromosomal deletion and 17 unaffected siblings, recruited as part of the Experiences of Children with Variants in the number of copies from Cardiff University. (ECHO), led by Prof. van den Bree. They measured correlations between EEG patterns of sleep and psychiatric symptoms, as well as performance on a recall test the next morning.
They found that the 22q11.2DS group had significant alterations in sleep patterns, including a higher proportion of N3 NREM (slow-wave sleep) sleep and lower proportions of N1 (the first and lightest stage of sleep) and sleep. rapid eye movement (REM). compared to his siblings.
Those who carried the chromosomal deletion also had increased EEG power for both 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 took part in a 2D object location task before bed, where they had to remember where matching cards 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 chromosomal deletion, higher amplitudes were associated with greater accuracy on 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 on 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 caused by the 22q11.2 deletion were partially mediated by differences in sleep EEG. “Our EEG findings taken together suggest a complex picture of the neurophysiology of sleep at 22q11.2DS and highlight differences that could serve as potential biomarkers for 22q11.2-associated neurodevelopmental syndromes,” concluded co-senior author Matt Jones, Professor Research Neuroscience at the University of Bristol, UK.
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“Further studies will now be needed to clarify the relationship between psychiatric symptoms, EEG measures of sleep and neurodevelopment, with a view to identifying markers of brain circuitry dysfunction that could inform clinicians which patients are at higher risk and support treatment decisions”.
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