White matter microstructure differences between 15q11.2 copy number variation carriers and non-carriers in...

Area of Science:

• Neuroimaging
• Genetics
• Neurobiology

Background:

• The 15q11.2 BP1-BP2 copy number variant (CNV) is linked to neurodevelopmental and psychiatric conditions.
• Its long-term effects on white matter microstructure (WMM) in adulthood are not well understood.

Purpose of the Study:

• To investigate the long-term neurobiological effects of the 15q11.2 BP1-BP2 CNV on WMM in mid-to-late adulthood.
• To compare WMM parameters between deletion carriers, duplication carriers, and non-carriers using advanced diffusion MRI techniques.

Main Methods:

• Utilized UK Biobank diffusion MRI data from 15q11.2 BP1-BP2 deletion (n=126) and duplication (n=131) carriers, and matched non-carriers (n=1260-1310).
• Employed multiple advanced diffusion MRI approaches beyond DTI to assess WMM.
• Projected all metrics onto the WM skeleton for group comparisons.

Main Results:

• Identified region-level differences in WMM between 15q11.2 BP1-BP2 deletion carriers and non-carriers.
• Observed altered microstructural organization in the corpus callosum, cingulum, hippocampus, and uncinate fasciculus.
• Most significant differences, indicating lower diffusivity and higher fractional anisotropy, kurtosis, axonal water fraction, and intra-neurite volume fraction, were detected in the corpus callosum.

Conclusions:

• The 15q11.2 deletion affects WMM in the corpus callosum during mid-to-late life.
• Advanced diffusion MRI suggests altered axonal density or microstructural organization, potentially due to pathological axonal overgrowth and myelination abnormalities.
• These findings offer explanations for developmental and psychiatric differences observed in deletion carriers.