The Hidden Architecture of Brain Structural Variability in 22q11.2 Deletion Syndrome: A Multi-site Study
Rune Boen1, Kathleen P O'Hora1, Hoki Fung1
1Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior and Department of Psychology, University of California Los Angeles, Los Angeles, CA, USA.
Medrxiv : the Preprint Server for Health Sciences
|June 4, 2026
Summary
22q11.2 deletion syndrome (22q11DS) alters brain structure, showing widespread changes and region-specific variability. These structural differences align with neurotransmitter pathways and development, suggesting targets for intervention.
Area of Science:
- Neuroscience
- Genetics
- Psychiatry
Background:
- 22q11.2 deletion syndrome (22q11DS) is a significant genetic risk factor for neuropsychiatric disorders.
- It profoundly impacts brain structure, but uniform vs. variable effects remain unclear.
- Identifying these features is crucial for targeted interventions.
Purpose of the Study:
- To pinpoint brain regions with consistent and variable effects of 22q11DS.
- To investigate alignment with normative neurotransmitter receptor distributions.
- To examine relationships with cortical growth trajectories.
Main Methods:
- Multisite cross-sectional case-control study.
- T1-weighted brain MRI data from 438 individuals with 22q11DS and 380 controls.
- Standardized processing and statistical site-adjustment.
Main Results:
- Individuals with 22q11DS exhibited widespread mean differences in cortical thickness and surface area.
- Greater regional heterogeneity in cortical thickness and surface area was observed in 22q11DS.
- Cortical thickness alterations spatially overlapped with glutamatergic and GABAergic receptor-rich regions.
Conclusions:
- 22q11DS has broad effects on cortical structure, indicating global developmental mechanisms.
- Region-specific variability suggests individualized neurobiological processes.
- Structural variability aligns with excitatory-inhibitory signaling and cortical development, offering intervention targets.
