Abnormalities in gray matter microstructure in young adults with 22q11.2 deletion syndrome.


Journal

NeuroImage. Clinical
ISSN: 2213-1582
Titre abrégé: Neuroimage Clin
Pays: Netherlands
ID NLM: 101597070

Informations de publication

Date de publication:
2019
Historique:
received: 04 07 2018
revised: 19 11 2018
accepted: 25 11 2018
pubmed: 14 12 2018
medline: 18 12 2019
entrez: 8 12 2018
Statut: ppublish

Résumé

22q11.2 Deletion Syndrome (22q11DS) is a genetic, neurodevelopmental disorder characterized by a chromosomal deletion and a distinct cognitive profile. Although abnormalities in the macrostructure of the cortex have been identified in individuals with 22q11DS, it is not known if there are additional microstructural changes in gray matter regions in this syndrome, and/or if such microstructural changes are associated with cognitive functioning. This study employed a novel diffusion MRI measure, the Heterogeneity of Fractional Anisotropy (HFA), to examine variability in the microstructural organization of the cortex in healthy young adults (N = 30) and those with 22q11DS (N = 56). Diffusion MRI, structural MRI, clinical and cognitive data were acquired. Compared to controls, individuals with 22q11DS evinced increased HFA in cortical association (p = .003, d = 0.86) and paralimbic (p < .0001, d = 1.2) brain areas, whereas no significant differences were found between the two groups in primary cortical brain areas. Additionally, increased HFA of the right paralimbic area was associated with poorer performance on tests of response inhibition, i.e., the Stroop Test (rho = -0.37 p = .005) and the Gordon Diagnostic System Vigilance Commission (rho = -0.41 p = .002) in the 22q11DS group. No significant correlations were found between HFA and cognitive abilities in the healthy control group. These findings suggest that cortical microstructural disorganization may be a neural correlate of response inhibition in individuals with 22q11DS. Given that the migration pattern of neural crest cells is disrupted at the time of early brain development in 22q11DS, we hypothesize that these neural alterations may be neurodevelopmental in origin, and reflect cortical dysfunction associated with cognitive deficits.

Sections du résumé

BACKGROUND
22q11.2 Deletion Syndrome (22q11DS) is a genetic, neurodevelopmental disorder characterized by a chromosomal deletion and a distinct cognitive profile. Although abnormalities in the macrostructure of the cortex have been identified in individuals with 22q11DS, it is not known if there are additional microstructural changes in gray matter regions in this syndrome, and/or if such microstructural changes are associated with cognitive functioning.
METHODS
This study employed a novel diffusion MRI measure, the Heterogeneity of Fractional Anisotropy (HFA), to examine variability in the microstructural organization of the cortex in healthy young adults (N = 30) and those with 22q11DS (N = 56). Diffusion MRI, structural MRI, clinical and cognitive data were acquired.
RESULTS
Compared to controls, individuals with 22q11DS evinced increased HFA in cortical association (p = .003, d = 0.86) and paralimbic (p < .0001, d = 1.2) brain areas, whereas no significant differences were found between the two groups in primary cortical brain areas. Additionally, increased HFA of the right paralimbic area was associated with poorer performance on tests of response inhibition, i.e., the Stroop Test (rho = -0.37 p = .005) and the Gordon Diagnostic System Vigilance Commission (rho = -0.41 p = .002) in the 22q11DS group. No significant correlations were found between HFA and cognitive abilities in the healthy control group.
CONCLUSIONS
These findings suggest that cortical microstructural disorganization may be a neural correlate of response inhibition in individuals with 22q11DS. Given that the migration pattern of neural crest cells is disrupted at the time of early brain development in 22q11DS, we hypothesize that these neural alterations may be neurodevelopmental in origin, and reflect cortical dysfunction associated with cognitive deficits.

Identifiants

pubmed: 30522971
pii: S2213-1582(18)30364-4
doi: 10.1016/j.nicl.2018.101611
pmc: PMC6411601
pii:
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

101611

Subventions

Organisme : NIMH NIH HHS
ID : R01 MH108574
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH097979
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG042512
Pays : United States
Organisme : NCCIH NIH HHS
ID : R21 AT008865
Pays : United States
Organisme : NIDA NIH HHS
ID : R21 DA042271
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH111917
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD090641
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH085953
Pays : United States

Informations de copyright

Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Auteurs

Zora Kikinis (Z)

Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Zora Kikinis, 1249 Boylston Street, Boston, MA 02215, USA. Electronic address: zora@bwh.harvard.edu.

Nikos Makris (N)

Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Zora Kikinis, 1249 Boylston Street, Boston, MA 02215, USA; Departments of Psychiatry and Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Valerie J Sydnor (VJ)

Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Zora Kikinis, 1249 Boylston Street, Boston, MA 02215, USA.

Sylvain Bouix (S)

Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Zora Kikinis, 1249 Boylston Street, Boston, MA 02215, USA.

Ofer Pasternak (O)

Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Zora Kikinis, 1249 Boylston Street, Boston, MA 02215, USA; Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Ioana L Coman (IL)

Department of Psychiatry, SUNY Upstate Medical University, Syracuse, NY, USA; Department of Computer Science, SUNY Oswego, Oswego, NY, USA.

Kevin M Antshel (KM)

Department of Psychiatry, SUNY Upstate Medical University, Syracuse, NY, USA; Department of Psychology, Syracuse University, Syracuse, NY, USA.

Wanda Fremont (W)

Department of Psychiatry, SUNY Upstate Medical University, Syracuse, NY, USA.

Marek R Kubicki (MR)

Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Zora Kikinis, 1249 Boylston Street, Boston, MA 02215, USA; Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Martha E Shenton (ME)

Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Zora Kikinis, 1249 Boylston Street, Boston, MA 02215, USA; Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; VA Boston Healthcare System, Brockton, MA, USA.

Wendy R Kates (WR)

Department of Psychiatry, SUNY Upstate Medical University, Syracuse, NY, USA.

Yogesh Rathi (Y)

Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Zora Kikinis, 1249 Boylston Street, Boston, MA 02215, USA; Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

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