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. 2014 Jan;152(1):117-23.
doi: 10.1016/j.schres.2013.11.015. Epub 2013 Dec 8.

White matter abnormalities in 22q11.2 deletion syndrome: preliminary associations with the Nogo-66 receptor gene and symptoms of psychosis

Matthew D Perlstein  1 , Moeed R Chohan  1 , Ioana L Coman  1 , Kevin M Antshel  2 , Wanda P Fremont  1 , Matthew H Gnirke  1 , Zora Kikinis  3 , Frank A Middleton  4 , Petya D Radoeva  1 , Martha E Shenton  5 , Wendy R Kates  6
Affiliations

White matter abnormalities in 22q11.2 deletion syndrome: preliminary associations with the Nogo-66 receptor gene and symptoms of psychosis

Matthew D Perlstein et al. Schizophr Res. 2014 Jan.

Abstract

Background: This study utilized diffusion tensor imaging (DTI) to analyze white matter tractography in the anterior limb of the internal capsule (ALIC), fornix, and uncinate fasciculus (UF) of individuals with 22q11.2 deletion syndrome and controls. Aberrations in these tracts have been previously associated with schizophrenia. With up to 25% of individuals with 22q11.2DS developing schizophrenia in adulthood, we hypothesized reduction in structural integrity of these tracts, including an association with prodromal symptoms of psychosis. We further predicted an association between allelic variation in a functional polymorphism of the Nogo-66 receptor gene and 22q11.2DS white matter integrity.

Methods: Tractography was conducted using fiber assignment by streamline tracking algorithm in DTI Studio. Subjects were genotyped for the rs701428 SNP of the Nogo-66 receptor gene, and assessed for presence of prodromal symptoms.

Results: We found significant group differences between 22q11.2DS and controls in DTI metrics for all three tracts. DTI metrics of ALIC and UF were associated with prodromal symptoms in 22q11.2DS. Further, ALIC DTI metrics were associated with allelic variation of the rs701428 SNP of the Nogo-66 receptor gene in 22q11.2DS.

Conclusions: Alterations in DTI metrics suggest white matter microstructural anomalies of the ALIC, fornix, and UF in 22q11.2DS. Structural differences in ALIC appear to be associated with the Nogo-66 receptor gene, which has been linked to myelin-mediated axonal growth inhibition. Moreover, the association between psychosis symptoms and ALIC and UF metrics suggests that the Nogo-66 receptor gene may represent a susceptibility gene for psychosis through its disruption of white matter microstructure and myelin-associated axonal growth.

Keywords: Anterior limb of internal capsule; Diffusion tensor imaging (DTI); RTN4R gene; Uncinate fasciculus; Velo-cardio-facial syndrome; rs701428.

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Conflict of interest statement

Conflicts of Interest

The authors report no biomedical financial interests or potential conflicts of interest.

Figures

Figure 1
Figure 1
Study group differences for the left and right hemispheres of the anterior limb of the internal capsule (ALIC). DTI metrics include (A) fractional anisotropy (FA) and (B) radial diffusivity (RD).
Figure 2
Figure 2
Effect of allelic variation of the rs701428 SNP of the NoGo-66 receptor gene on DTI metrics in the ALIC for the left (L) and right (R) hemispheres. DTI metrics include (A) fractional anisotropy, and (B) radial diffusivity. Only individuals diagnosed with 22q11DS are included. Error bars reflect the standard deviation from the mean.
Figure 3
Figure 3
Association between ALIC DTI metrics and the positive symptom scale of the Scale of Prodromal Symptoms (SOPS). DTI metrics include (A) fractional anisotropy in the right ALIC, and (B) radial diffusivity in the left ALIC. DTI values were categorized as High or Low using a median split of the data.
Figure 4
Figure 4
Association between UF DTI metrics and the positive symptom scale of the Scale of Prodromal Symptoms (SOPS). DTI metrics include (A) radial diffusivity in the left UF, and (B) radial diffusivity in the right ALIC. DTI values were categorized as High or Low using a median split of the data.
See this image and copyright information in PMC

References

    1. Alba-Ferrara LM, de Erausquin GA. What does anisotropy measure? Insights from increased and decreased anisotropy in selective fiber tracts in schizophrenia. Front Integr Neurosci. 2013;7:9. - PMC - PubMed
    1. Alexander AL, Lee JE, Lazar M, Field AS. Diffusion tensor imaging of the brain. Neurotherapeutics. 2007;4(3):316–329. - PMC - PubMed
    1. Antshel KM, Aneja A, Strunge L, Peebles J, Fremont WP, Stallone K, Abdulsabur N, Higgins AM, Shprintzen RJ, Kates WR. Autistic spectrum disorders in velo-cardio facial syndrome (22q11.2 deletion) J Autism Dev Disord. 2007;37(9):1776–1786. - PubMed
    1. Antshel KM, Conchelos J, Lanzetta G, Fremont W, Kates WR. Behavior and corpus callosum morphology relationships in velocardiofacial syndrome (22q11.2 deletion syndrome) Psychiatry Res. 2005;138(3):235–245. - PubMed
    1. Antshel KM, Fremont W, Kates WR. The neurocognitive phenotype in velo-cardio-facial syndrome: a developmental perspective. Dev Disabil Res Rev. 2008;14(1):43–51. - PubMed

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