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Distinct white-matter aberrations in 22q11.2 deletion syndrome and patients at ultra-high risk for psychosis

Published online by Cambridge University Press:  19 May 2016

G. Bakker ,
M. W. A. Caan ,
R. S. Schluter ,
O. J. N Bloemen ,
F. da Silva- Alves ,
M. B. de Koning ,
E. Boot ,
W. A. M. Vingerhoets ,
D. H. Nieman  and
L. de Haan
...Show all authors
G. Bakker*
Affiliation:
Department of Psychiatry & Psychology, University of Maastricht, The Netherlands Department of Nuclear Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
M. W. A. Caan
Affiliation:
Department of Radiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
R. S. Schluter
Affiliation:
Department of Radiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands Department of Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
O. J. N Bloemen
Affiliation:
Department of Psychiatry & Psychology, University of Maastricht, The Netherlands GGZ Centraal, Center for Mental Health Care Innova, Amersfoort, The Netherlands
F. da Silva- Alves
Affiliation:
Department of Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
M. B. de Koning
Affiliation:
Department of Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands Arkin Mental Health Care, Amsterdam, The Netherlands
E. Boot
Affiliation:
Department of Nuclear Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands The Dalglish Family Hearts and Minds Clinic for Adults with 22q11.2 Deletion Syndrome, Toronto, Ontario, Canada
W. A. M. Vingerhoets
Affiliation:
Department of Psychiatry & Psychology, University of Maastricht, The Netherlands Department of Nuclear Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
D. H. Nieman
Affiliation:
Department of Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
L. de Haan
Affiliation:
Department of Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
J. Booij
Affiliation:
Department of Nuclear Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
T. A. M. J. van Amelsvoort
Affiliation:
Department of Psychiatry & Psychology, University of Maastricht, The Netherlands
*
*Address for correspondence: G. Bakker, MSc, Department of Psychiatry and Psychology, Maastricht University, P.O. Box 616 (Vijv-SN2), 6200 MD Maastricht, The Netherlands. (Email: geor.bakker@maastrichtuniversity.nl)
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Abstract

Background

Patients with a deletion at chromosome 22q11.2 (22q11DS) have 30% lifetime risk of developing a psychosis. People fulfilling clinical criteria for ultra-high risk (UHR) for psychosis have 30% risk of developing a psychosis within 2 years. Both high-risk groups show white-matter (WM) abnormalities in microstructure and volume compared to healthy controls (HC), which have been related to psychotic symptoms. Comparisons of WM pathology between these two groups may specify WM markers related to genetic and clinical risk factors.

Method

Fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD) were assessed using diffusion tensor magnetic resonance imaging (MRI), and WM volume with structural MRI, in 23 UHR patients, 21 22q11DS patients, and 33 HC.

Results

Compared to UHR patients 22q11DS patients had (1) lower AD and RD in corpus callosum (CC), cortical fasciculi, and anterior thalamic radiation (ATR), (2) higher FA in CC and ATR, and (3) lower occipital and superior temporal gyrus WM volume. Compared to HC, 22q11DS patients had (1) lower AD and RD throughout cortical fasciculi and (2) higher FA in ATR, CC and inferior fronto-occipital fasciculus. Compared to HC, UHR patients had (1) higher mean MD, RD, and AD in CC, ATR and cortical fasciculi, (2) no differences in FA.

Conclusions

UHR and 22q11DS patients share a susceptibility for developing psychosis yet were characterized by distinct patterns of WM alterations relative to HC. While UHR patients were typified by signs suggestive of aberrant myelination, 22q11DS subjects showed signs suggestive of lower axonal integrity.

Keywords

22q11.2 deletion syndromebiomarkerspsychosisTBSSultra-high riskwhite-matter microstructurewhite-matter volume
Type
Original Articles
Information
Psychological Medicine , Volume 46 , Issue 11 , August 2016 , pp. 2299 - 2311
Copyright
Copyright © Cambridge University Press 2016 

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