A new study demonstrates that young people with a genetic variation that increases the risk of psychiatric disorders have significantly different brain activity while they sleep. 22q11.2DS is caused by a gene deletion of roughly 30 genes on chromosome 22 and affects one in every three thousand births. It raises the chance of epileptic seizures, autism spectrum disorder (ASD), intellectual impairment, and attention-deficit hyperactivity disorder (ADHD).
Additionally, it ranks highly among the biological risk factors for schizophrenia. Uncertainty surrounds the molecular processes that underlie the psychological symptoms of 22q11.2DS, though. ‘We have recently shown that the majority of young people with 22q11.2DS have sleep problems, particularly insomnia and sleep fragmentation, that are linked with psychiatric disorders’, says co-senior author Marianne van den Bree, Professor of Psychological Medicine at Cardiff University, UK, adding, ‘However, our previous analysis was based on parents reporting on sleep quality of their children, and the neurophysiology what`s happening to brain activity has not yet been explored’.
An electroencephalogram (EEG) is a recognised method of assessing brain activity while you are sleeping. This monitors electrical activity as you sleep and includes spindle and slow-wave (SW) oscillation patterns. These characteristics of non-rapid eye movement (NREM) sleep are considered to support the development of the brain and memory. ‘Because sleep EEG is known to be altered in many neurodevelopmental disorders, the properties and coordination of these alterations can be used as biomarkers for psychiatric dysfunction’, explained lead author Nick Donnelly, Clinical Lecturer in General Adult Psychiatry at the University of Bristol, UK.
In order to investigate this in 22q11.2DS, the team recruited 28 children between the ages of 6 and 20 who had the chromosome deletion as well as 17 siblings who were unaffected, as part of the Cardiff University Experiences of Children with Copy Number Variants (ECHO) study, which is headed by Prof. van den Bree. They examined the relationships between mental symptoms and sleep EEG patterns, as well as how well the subjects performed in a morning recollection test.
They discovered that, in comparison to their siblings, the group with 22q11.2DS showed substantial differences in their sleep patterns, with higher proportions of N3 NREM sleep (slow-wave sleep) and lower proportions of N1 (the first and lightest sleep stage) and rapid eye movement (REM) sleep.
Additionally, those who had the chromosomal deletion exhibited higher slow-wave oscillation and spindle EEG power. Additionally, there was a tighter link between the spindle and slow-wave EEG characteristics and an increase in the frequency and density of spindle patterns in the 22q112.DS group. The connections inside and between the cortex and thalamus, the brain regions that produce these oscillations, may have changed as a result of these modifications.
Before going to bed, participants had to remember where matching cards were on a screen for a 2D object-finding test. The group discovered that larger spindle and SW amplitudes were related to decreased accuracy in those with 22q11.2DS when they were assessed again on the identical task in the morning.
In contrast, larger amplitudes were associated with greater accuracy in the morning memory test in subjects without chromosomal deletion. Finally, the researchers used a statistical technique known as mediation to calculate the effect of the variations in sleep patterns on mental symptoms in the two groups.
They determined the overall impact of genotype on IQ and psychiatric measurements, as well as the indirect (mediated) impact of EEG measurements. Finally, they computed the percentage of the overall impact that may be mediated by EEG patterns. They discovered that the 22q11 was responsible for the impacts on anxiety, ADHD, and ASD. 2 deletions were mediated in part by variations in sleep EEG.
‘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-senior author Matt Jones, Professorial Research Fellow in Neuroscience, University of Bristol, UK.