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The largest diffusion MRI study reveals widespread white matter microstructure alterations in 22q11.2 deletion syndrome (22q11DS), impacting major brain connections and correlating with psychosis risk.

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Area of Science:

  • Neuroimaging
  • Genetics
  • Neurodevelopmental Disorders

Background:

  • 22q11.2 deletion syndrome (22q11DS) is a neurodevelopmental condition linked to psychosis and brain disorders.
  • Previous diffusion MRI studies in 22q11DS reported inconsistent findings due to small sample sizes and varied methodologies.

Purpose of the Study:

  • To investigate white matter (WM) microstructure alterations in the largest cohort of 22q11DS patients to date.
  • To examine the relationship between WM microstructure abnormalities and psychosis in 22q11DS.

Main Methods:

  • Utilized diffusion magnetic resonance imaging (dMRI) on 334 individuals with 22q11DS and 260 controls (ages 6-52).
  • Applied harmonization protocols from the ENIGMA-DTI working group for dMRI data analysis.
  • Analyzed mean, axial, and radial diffusivities, and fractional anisotropy (FA) across brain white matter tracts.

Main Results:

  • Identified widespread reductions in diffusivity across multiple WM regions in 22q11DS, particularly in cortico-cortical and cortico-thalamic fibers.
  • Observed higher axial diffusivity in the internal capsule (IC) and varied FA patterns in 22q11DS.
  • Found more pronounced diffusivity reductions in individuals with 22q11DS who experienced psychotic illness.

Conclusions:

  • The 22q11.2 deletion significantly impacts WM microstructure, especially in major cortico-cortical connections.
  • These WM abnormalities may stem from disrupted neurogenesis of projection neurons.
  • Findings provide crucial insights into the neurobiological underpinnings of 22q11DS and associated psychiatric risks.