PT  - JOURNAL ARTICLE
AU  - Julia P. Owen
AU  - Yi Shin Chang
AU  - Nicholas J. Pojman
AU  - Polina Bukshpun
AU  - Mari L.J. Wakahiro
AU  - Elysa J. Marco
AU  - Jeffrey I. Berman
AU  - John E. Spiro
AU  - Wendy K. Chung
AU  - Randy L. Buckner
AU  - Timothy P.L. Roberts
AU  - Srikantan S. Nagarajan
AU  - Elliott H. Sherr
AU  - Pratik Mukherjee
TI  - Aberrant White Matter Microstructure in Children with 16p11.2 Deletions
AID  - 10.1523/JNEUROSCI.4495-13.2014
DP  - 2014 Apr 30
TA  - The Journal of Neuroscience
PG  - 6214--6223
VI  - 34
IP  - 18
4099  - http://www.jneurosci.org/content/34/18/6214.short
4100  - http://www.jneurosci.org/content/34/18/6214.full
SO  - J. Neurosci.2014 Apr 30; 34
AB  - Copy number variants (CNVs) of the chromosomal locus 16p11.2, consisting of either deletions or duplications, have been implicated in autism, schizophrenia, epilepsy, and other neuropsychiatric disorders. Since abnormal white matter microstructure can be seen in these more broadly defined clinical disorders, we used diffusion magnetic resonance imaging and tract-based spatial statistics to investigate white matter microstructural integrity in human children with 16p11.2 deletions. We show that deletion carriers, compared with typically developing matched controls, have increased axial diffusivity (AD) in many major central white matter tracts, including the anterior corpus callosum as well as bilateral internal and external capsules. Higher AD correlated with lower nonverbal IQ in the deletion carriers, but not controls. Increases in fractional anisotropy and mean diffusivity were also found in some of the same tracts with elevated AD. Closer examination with neurite orientation dispersion and density imaging revealed that fiber orientation dispersion was decreased in some central white matter tracts. Notably, these alterations of white matter are unlike microstructural differences reported for any other neurodevelopmental disorders, including autism spectrum disorders that have phenotypic overlap with the deletion carriers. These findings suggest that deletion of the 16p11.2 locus is associated with a unique widespread pattern of aberrant white matter microstructure that may underlie the impaired cognition characteristic of this CNV.