Source-based morphometry reveals structural brain pattern abnormalities in 22q11.2 deletion syndrome

Ruiyang Ge; Christopher R.K. Ching; Anne S. Bassett; Leila Kushan; Kevin M. Antshel; Therese van Amelsvoort; Geor Bakker; Nancy J. Butcher; Linda E. Campbell; Eva W.C. Chow; Michael Craig; Nicolas A. Crossley; Adam Cunningham; Eileen Daly; Joanne L. Doherty; Courtney A. Durdle; Beverly S. Emanuel; Ania Fiksinski; Jennifer K. Forsyth; Wanda Fremont; Naomi J. Goodrich-Hunsaker; Maria Gudbrandsen; Raquel E. Gur; Maria Jalbrzikowski; Wendy R. Kates; Amy Lin; David E.J. Linden; Kathryn L. McCabe; Donna McDonald-McGinn; Hayley Moss; Declan G. Murphy; Kieran C. Murphy; Michael J. Owen; Julio E. Villalon-Reina; Gabriela M. Repetto; David R. Roalf; Kosha Ruparel; J. Eric Schmitt; Sanne Schuite-Koops; Kathleen Angkustsiri; Daqiang Sun; Ariana Vajdi; Marianne van den Bree; Jacob Vorstman; Paul M. Thompson; Fidel Vila-Rodriguez; Carrie E. Bearden

doi:10.1002/hbm.26553

Source-based morphometry reveals structural brain pattern abnormalities in 22q11.2 deletion syndrome

Ruiyang Ge
, Christopher R.K. Ching
, Anne S. Bassett
, Leila Kushan
, Kevin M. Antshel
, Therese van Amelsvoort
, Geor Bakker
, Nancy J. Butcher
, Linda E. Campbell
, Eva W.C. Chow
, Michael Craig
, Nicolas A. Crossley
, Adam Cunningham
, Eileen Daly
, Joanne L. Doherty
, Courtney A. Durdle
, Beverly S. Emanuel
, Ania Fiksinski
, Jennifer K. Forsyth
, Wanda Fremont

Naomi J. Goodrich-Hunsaker, Maria Gudbrandsen, Raquel E. Gur, Maria Jalbrzikowski, Wendy R. Kates, Amy Lin, David E.J. Linden, Kathryn L. McCabe, Donna McDonald-McGinn, Hayley Moss, Declan G. Murphy, Kieran C. Murphy, Michael J. Owen, Julio E. Villalon-Reina, Gabriela M. Repetto, David R. Roalf, Kosha Ruparel, J. Eric Schmitt, Sanne Schuite-Koops, Kathleen Angkustsiri, Daqiang Sun, Ariana Vajdi, Marianne van den Bree, Jacob Vorstman, Paul M. Thompson, Fidel Vila-Rodriguez^*, Carrie E. Bearden^*

^*Corresponding author for this work

UBC University of British Columbia
Djavad Mowafaghian Centre for Brain Health
USC University of Southern California
Centre for Addiction and Mental Health
University Health Network
University Health Network, Toronto
UCLA Semel Institute for Neuroscience and Human Behavior
Syracuse University
Maastricht University
The Hospital for Sick Children Research Institute
Pontificia Universidad Catolica de Chile
Division of Psychological Medicine & Clinical Neurosciences
Cardiff University
UC Davis MIND Institute and Department of Psychiatry and Behavioral Sciences
University of California, Santa Barbara
The Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
University of Pennsylvania
UMC University Medical Center Utrecht
University of Washington
SUNY Upstate Medical University
University of Utah
Department of Psychology and Neuroscience
King's College London
Centre for Research in Psychological Wellbeing (CREW)
University of Roehampton
Harvard Medical School
Boston Children's Hospital
University of California
University of Newcastle, Australia
School of Medicine
Royal College of Surgeons of Ireland
Universidad del Desarrollo
University Medical Center Groningen
Kaiser Permanente Bernard J. Tyson School of Medicine
Vancouver General Hospital, The Prostate Centre, University of British Columbia, Faculty of Medicine

Research output: Contribution to journal › Article › peer-review

6 Citations (Scopus)

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Abstract

22q11.2 deletion syndrome (22q11DS) is the most frequently occurring microdeletion in humans. It is associated with a significant impact on brain structure, including prominent reductions in gray matter volume (GMV), and neuropsychiatric manifestations, including cognitive impairment and psychosis. It is unclear whether GMV alterations in 22q11DS occur according to distinct structural patterns. Then, 783 participants (470 with 22q11DS: 51% females, mean age [SD] 18.2 [9.2]; and 313 typically developing [TD] controls: 46% females, mean age 18.0 [8.6]) from 13 datasets were included in the present study. We segmented structural T1-weighted brain MRI scans and extracted GMV images, which were then utilized in a novel source-based morphometry (SBM) pipeline (SS-Detect) to generate structural brain patterns (SBPs) that capture co-varying GMV. We investigated the impact of the 22q11.2 deletion, deletion size, intelligence quotient, and psychosis on the SBPs. Seventeen GMV-SBPs were derived, which provided spatial patterns of GMV covariance associated with a quantitative metric (i.e., loading score) for analysis. Patterns of topographically widespread differences in GMV covariance, including the cerebellum, discriminated individuals with 22q11DS from healthy controls. The spatial extents of the SBPs that revealed disparities between individuals with 22q11DS and controls were consistent with the findings of the univariate voxel-based morphometry analysis. Larger deletion size was associated with significantly lower GMV in frontal and occipital SBPs; however, history of psychosis did not show a strong relationship with these covariance patterns. 22q11DS is associated with distinct structural abnormalities captured by topographical GMV covariance patterns that include the cerebellum. Findings indicate that structural anomalies in 22q11DS manifest in a nonrandom manner and in distinct covarying anatomical patterns, rather than a diffuse global process. These SBP abnormalities converge with previously reported cortical surface area abnormalities, suggesting disturbances of early neurodevelopment as the most likely underlying mechanism.

Original language	English
Article number	e26553
Number of pages	15
Journal	Human Brain Mapping
Volume	45
Issue number	1
DOIs	https://doi.org/10.1002/hbm.26553
Publication status	Published - 12 Jan 2024

Keywords

22q11 deletion syndrome
gray matter volume
magnetic resonnance imaging
source-based morphometry

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Source-based morphometry reveals structural brain pattern abnormalities in 22q11.2 deletion syndrome_Version of RecordFinal published version, 11 MBLicence: CC BY-NC

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Ge, R., Ching, C. R. K., Bassett, A. S., Kushan, L., Antshel, K. M., van Amelsvoort, T., Bakker, G., Butcher, N. J., Campbell, L. E., Chow, E. W. C., Craig, M., Crossley, N. A., Cunningham, A., Daly, E., Doherty, J. L., Durdle, C. A., Emanuel, B. S., Fiksinski, A., Forsyth, J. K., ... Bearden, C. E. (2024). Source-based morphometry reveals structural brain pattern abnormalities in 22q11.2 deletion syndrome. Human Brain Mapping, 45(1), Article e26553. https://doi.org/10.1002/hbm.26553

@article{cb222b0ca92846bf90582b039c9d50ba,

title = "Source-based morphometry reveals structural brain pattern abnormalities in 22q11.2 deletion syndrome",

abstract = "22q11.2 deletion syndrome (22q11DS) is the most frequently occurring microdeletion in humans. It is associated with a significant impact on brain structure, including prominent reductions in gray matter volume (GMV), and neuropsychiatric manifestations, including cognitive impairment and psychosis. It is unclear whether GMV alterations in 22q11DS occur according to distinct structural patterns. Then, 783 participants (470 with 22q11DS: 51\% females, mean age [SD] 18.2 [9.2]; and 313 typically developing [TD] controls: 46\% females, mean age 18.0 [8.6]) from 13 datasets were included in the present study. We segmented structural T1-weighted brain MRI scans and extracted GMV images, which were then utilized in a novel source-based morphometry (SBM) pipeline (SS-Detect) to generate structural brain patterns (SBPs) that capture co-varying GMV. We investigated the impact of the 22q11.2 deletion, deletion size, intelligence quotient, and psychosis on the SBPs. Seventeen GMV-SBPs were derived, which provided spatial patterns of GMV covariance associated with a quantitative metric (i.e., loading score) for analysis. Patterns of topographically widespread differences in GMV covariance, including the cerebellum, discriminated individuals with 22q11DS from healthy controls. The spatial extents of the SBPs that revealed disparities between individuals with 22q11DS and controls were consistent with the findings of the univariate voxel-based morphometry analysis. Larger deletion size was associated with significantly lower GMV in frontal and occipital SBPs; however, history of psychosis did not show a strong relationship with these covariance patterns. 22q11DS is associated with distinct structural abnormalities captured by topographical GMV covariance patterns that include the cerebellum. Findings indicate that structural anomalies in 22q11DS manifest in a nonrandom manner and in distinct covarying anatomical patterns, rather than a diffuse global process. These SBP abnormalities converge with previously reported cortical surface area abnormalities, suggesting disturbances of early neurodevelopment as the most likely underlying mechanism.",

keywords = "22q11 deletion syndrome, gray matter volume, magnetic resonnance imaging, source-based morphometry",

author = "Ruiyang Ge and Ching, \{Christopher R.K.\} and Bassett, \{Anne S.\} and Leila Kushan and Antshel, \{Kevin M.\} and \{van Amelsvoort\}, Therese and Geor Bakker and Butcher, \{Nancy J.\} and Campbell, \{Linda E.\} and Chow, \{Eva W.C.\} and Michael Craig and Crossley, \{Nicolas A.\} and Adam Cunningham and Eileen Daly and Doherty, \{Joanne L.\} and Durdle, \{Courtney A.\} and Emanuel, \{Beverly S.\} and Ania Fiksinski and Forsyth, \{Jennifer K.\} and Wanda Fremont and Goodrich-Hunsaker, \{Naomi J.\} and Maria Gudbrandsen and Gur, \{Raquel E.\} and Maria Jalbrzikowski and Kates, \{Wendy R.\} and Amy Lin and Linden, \{David E.J.\} and McCabe, \{Kathryn L.\} and Donna McDonald-McGinn and Hayley Moss and Murphy, \{Declan G.\} and Murphy, \{Kieran C.\} and Owen, \{Michael J.\} and Villalon-Reina, \{Julio E.\} and Repetto, \{Gabriela M.\} and Roalf, \{David R.\} and Kosha Ruparel and Schmitt, \{J. Eric\} and Sanne Schuite-Koops and Kathleen Angkustsiri and Daqiang Sun and Ariana Vajdi and \{van den Bree\}, Marianne and Jacob Vorstman and Thompson, \{Paul M.\} and Fidel Vila-Rodriguez and Bearden, \{Carrie E.\}",

note = "Funding Information: was reported support by U54EB020403 from the Big Data to Knowledge (BD2K) Program; R01MH116147‐04; R01AG058854‐02; R01MH129742‐01. GB was supported by European Commision grant: QLGU‐CT‐2001‐01081; NWO‐Veni grant 2006 ‐916.76.048; Dutch Brain Foundation: 15F07(2).55. was supported by the Dalglish Family Chair in 22q11.2 Deletion Syndrome, Canadian Institutes of Health Research (CIHR) (MOP‐313331 and MOP‐111238), and NIMH grant number U01MH119741‐01. was supported by the NIH via grants NIMH. reports support from Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No. 115300 (for EU‐AIMS) and No. 777394 (for AIMS‐2‐TRIALS). was supported by a Wellcome Trust Clinical Research Training Fellowship (102003/Z/13/Z). was supported by NIH grants K01MH112774 and R01MH129636 and a Next Generation Award from the Tommy Fuss Center for Neuropsychiatric Research. was supported by NIH (R01 MH064824). reports support by Wellcome Trust Strategic Award “DEFINE”. receives research support from NIH via grant 5U01MH119737‐04. reports support by Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No. 115300 (for EU‐AIMS) and No. 777394 (for AIMS‐2‐TRIALS). was supported by the NIH via grants NIMH U01MH119738 and U01MH101724 and the MRC via grant MR/T033045/1, MR/N022572/1, and MR/L011166/1. was supported by the NIH via grants R01MH129742 and R01MH116147. was supported by Fondecyt grants 1171014 and 1211411, and ACT 192064 (ANID‐Chile). was supported by NIH R01MH107018 and U54HD079125. was supported by the NIH via grants NIMH U01MH119758 and U01MH101724 and the MRC via grant MR/T033045/1, MR/N022572/1 and MR/L011166/1. was supported by The SickKids Psychiatry Associates Chair in Developmental Psychopathology and NIMH U01MH119741‐01. was supported by the NIH via grants R01MH129742 and R01MH116147. was supported by U54EB020403 from the Big Data to Knowledge (BD2K) Program, NIMH R01MH085953, NIMH U01MH101719. receives research support from CIHR, Brain Canada, Michael Smith Foundation for Health Research, Vancouver Coastal Health Research Institute, and Weston Brain Institute for investigator‐initiated research. Philanthropic support from Seedlings Foundation. In‐kind equipment supports for this investigator‐initiated trial from MagVenture. He has received honoraria for participation in an advisory board for Allergan. CC ASB TvA ED JLD MJ WRK DL DMM DGM MJO JVR GMR KA MvdB JV PMT CEB FVR Funding Information: CC was reported support by U54EB020403 from the Big Data to Knowledge (BD2K) Program; R01MH116147-04; R01AG058854-02; R01MH129742-01. GB was supported by European Commision grant: QLGU-CT-2001-01081; NWO-Veni grant 2006 -916.76.048; Dutch Brain Foundation: 15F07(2).55. ASB was supported by the Dalglish Family Chair in 22q11.2 Deletion Syndrome, Canadian Institutes of Health Research (CIHR) (MOP-313331 and MOP-111238), and NIMH grant number U01MH119741-01. TvA was supported by the NIH via grants NIMH. ED reports support from Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No. 115300 (for EU-AIMS) and No. 777394 (for AIMS-2-TRIALS). JLD was supported by a Wellcome Trust Clinical Research Training Fellowship (102003/Z/13/Z). MJ was supported by NIH grants K01MH112774 and R01MH129636 and a Next Generation Award from the Tommy Fuss Center for Neuropsychiatric Research. WRK was supported by NIH (R01 MH064824). DL reports support by Wellcome Trust Strategic Award “DEFINE”. DMM receives research support from NIH via grant 5U01MH119737-04. DGM reports support by Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No. 115300 (for EU-AIMS) and No. 777394 (for AIMS-2-TRIALS). MJO was supported by the NIH via grants NIMH U01MH119738 and U01MH101724 and the MRC via grant MR/T033045/1, MR/N022572/1, and MR/L011166/1. JVR was supported by the NIH via grants R01MH129742 and R01MH116147. GMR was supported by Fondecyt grants 1171014 and 1211411, and ACT 192064 (ANID-Chile). KA was supported by NIH R01MH107018 and U54HD079125. MvdB was supported by the NIH via grants NIMH U01MH119758 and U01MH101724 and the MRC via grant MR/T033045/1, MR/N022572/1 and MR/L011166/1. JV was supported by The SickKids Psychiatry Associates Chair in Developmental Psychopathology and NIMH U01MH119741-01. PMT was supported by the NIH via grants R01MH129742 and R01MH116147. CEB was supported by U54EB020403 from the Big Data to Knowledge (BD2K) Program, NIMH R01MH085953, NIMH U01MH101719. FVR receives research support from CIHR, Brain Canada, Michael Smith Foundation for Health Research, Vancouver Coastal Health Research Institute, and Weston Brain Institute for investigator-initiated research. Philanthropic support from Seedlings Foundation. In-kind equipment supports for this investigator-initiated trial from MagVenture. He has received honoraria for participation in an advisory board for Allergan. Publisher Copyright: {\textcopyright} 2024 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.",

year = "2024",

month = jan,

day = "12",

doi = "10.1002/hbm.26553",

language = "English",

volume = "45",

journal = "Human Brain Mapping",

issn = "1065-9471",

publisher = "Wiley-Liss Inc.",

number = "1",

}

Ge, R, Ching, CRK, Bassett, AS, Kushan, L, Antshel, KM, van Amelsvoort, T, Bakker, G, Butcher, NJ, Campbell, LE, Chow, EWC, Craig, M, Crossley, NA, Cunningham, A, Daly, E, Doherty, JL, Durdle, CA, Emanuel, BS, Fiksinski, A, Forsyth, JK, Fremont, W, Goodrich-Hunsaker, NJ, Gudbrandsen, M, Gur, RE, Jalbrzikowski, M, Kates, WR, Lin, A, Linden, DEJ, McCabe, KL, McDonald-McGinn, D, Moss, H, Murphy, DG, Murphy, KC, Owen, MJ, Villalon-Reina, JE, Repetto, GM, Roalf, DR, Ruparel, K, Schmitt, JE, Schuite-Koops, S, Angkustsiri, K, Sun, D, Vajdi, A, van den Bree, M, Vorstman, J, Thompson, PM, Vila-Rodriguez, F & Bearden, CE 2024, 'Source-based morphometry reveals structural brain pattern abnormalities in 22q11.2 deletion syndrome', Human Brain Mapping, vol. 45, no. 1, e26553. https://doi.org/10.1002/hbm.26553

TY - JOUR

T1 - Source-based morphometry reveals structural brain pattern abnormalities in 22q11.2 deletion syndrome

AU - Ge, Ruiyang

AU - Ching, Christopher R.K.

AU - Bassett, Anne S.

AU - Kushan, Leila

AU - Antshel, Kevin M.

AU - van Amelsvoort, Therese

AU - Bakker, Geor

AU - Butcher, Nancy J.

AU - Campbell, Linda E.

AU - Chow, Eva W.C.

AU - Craig, Michael

AU - Crossley, Nicolas A.

AU - Cunningham, Adam

AU - Daly, Eileen

AU - Doherty, Joanne L.

AU - Durdle, Courtney A.

AU - Emanuel, Beverly S.

AU - Fiksinski, Ania

AU - Forsyth, Jennifer K.

AU - Fremont, Wanda

AU - Goodrich-Hunsaker, Naomi J.

AU - Gudbrandsen, Maria

AU - Gur, Raquel E.

AU - Jalbrzikowski, Maria

AU - Kates, Wendy R.

AU - Lin, Amy

AU - Linden, David E.J.

AU - McCabe, Kathryn L.

AU - McDonald-McGinn, Donna

AU - Moss, Hayley

AU - Murphy, Declan G.

AU - Murphy, Kieran C.

AU - Owen, Michael J.

AU - Villalon-Reina, Julio E.

AU - Repetto, Gabriela M.

AU - Roalf, David R.

AU - Ruparel, Kosha

AU - Schmitt, J. Eric

AU - Schuite-Koops, Sanne

AU - Angkustsiri, Kathleen

AU - Sun, Daqiang

AU - Vajdi, Ariana

AU - van den Bree, Marianne

AU - Vorstman, Jacob

AU - Thompson, Paul M.

AU - Vila-Rodriguez, Fidel

AU - Bearden, Carrie E.

N1 - Funding Information: was reported support by U54EB020403 from the Big Data to Knowledge (BD2K) Program; R01MH116147‐04; R01AG058854‐02; R01MH129742‐01. GB was supported by European Commision grant: QLGU‐CT‐2001‐01081; NWO‐Veni grant 2006 ‐916.76.048; Dutch Brain Foundation: 15F07(2).55. was supported by the Dalglish Family Chair in 22q11.2 Deletion Syndrome, Canadian Institutes of Health Research (CIHR) (MOP‐313331 and MOP‐111238), and NIMH grant number U01MH119741‐01. was supported by the NIH via grants NIMH. reports support from Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No. 115300 (for EU‐AIMS) and No. 777394 (for AIMS‐2‐TRIALS). was supported by a Wellcome Trust Clinical Research Training Fellowship (102003/Z/13/Z). was supported by NIH grants K01MH112774 and R01MH129636 and a Next Generation Award from the Tommy Fuss Center for Neuropsychiatric Research. was supported by NIH (R01 MH064824). reports support by Wellcome Trust Strategic Award “DEFINE”. receives research support from NIH via grant 5U01MH119737‐04. reports support by Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No. 115300 (for EU‐AIMS) and No. 777394 (for AIMS‐2‐TRIALS). was supported by the NIH via grants NIMH U01MH119738 and U01MH101724 and the MRC via grant MR/T033045/1, MR/N022572/1, and MR/L011166/1. was supported by the NIH via grants R01MH129742 and R01MH116147. was supported by Fondecyt grants 1171014 and 1211411, and ACT 192064 (ANID‐Chile). was supported by NIH R01MH107018 and U54HD079125. was supported by the NIH via grants NIMH U01MH119758 and U01MH101724 and the MRC via grant MR/T033045/1, MR/N022572/1 and MR/L011166/1. was supported by The SickKids Psychiatry Associates Chair in Developmental Psychopathology and NIMH U01MH119741‐01. was supported by the NIH via grants R01MH129742 and R01MH116147. was supported by U54EB020403 from the Big Data to Knowledge (BD2K) Program, NIMH R01MH085953, NIMH U01MH101719. receives research support from CIHR, Brain Canada, Michael Smith Foundation for Health Research, Vancouver Coastal Health Research Institute, and Weston Brain Institute for investigator‐initiated research. Philanthropic support from Seedlings Foundation. In‐kind equipment supports for this investigator‐initiated trial from MagVenture. He has received honoraria for participation in an advisory board for Allergan. CC ASB TvA ED JLD MJ WRK DL DMM DGM MJO JVR GMR KA MvdB JV PMT CEB FVR Funding Information: CC was reported support by U54EB020403 from the Big Data to Knowledge (BD2K) Program; R01MH116147-04; R01AG058854-02; R01MH129742-01. GB was supported by European Commision grant: QLGU-CT-2001-01081; NWO-Veni grant 2006 -916.76.048; Dutch Brain Foundation: 15F07(2).55. ASB was supported by the Dalglish Family Chair in 22q11.2 Deletion Syndrome, Canadian Institutes of Health Research (CIHR) (MOP-313331 and MOP-111238), and NIMH grant number U01MH119741-01. TvA was supported by the NIH via grants NIMH. ED reports support from Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No. 115300 (for EU-AIMS) and No. 777394 (for AIMS-2-TRIALS). JLD was supported by a Wellcome Trust Clinical Research Training Fellowship (102003/Z/13/Z). MJ was supported by NIH grants K01MH112774 and R01MH129636 and a Next Generation Award from the Tommy Fuss Center for Neuropsychiatric Research. WRK was supported by NIH (R01 MH064824). DL reports support by Wellcome Trust Strategic Award “DEFINE”. DMM receives research support from NIH via grant 5U01MH119737-04. DGM reports support by Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No. 115300 (for EU-AIMS) and No. 777394 (for AIMS-2-TRIALS). MJO was supported by the NIH via grants NIMH U01MH119738 and U01MH101724 and the MRC via grant MR/T033045/1, MR/N022572/1, and MR/L011166/1. JVR was supported by the NIH via grants R01MH129742 and R01MH116147. GMR was supported by Fondecyt grants 1171014 and 1211411, and ACT 192064 (ANID-Chile). KA was supported by NIH R01MH107018 and U54HD079125. MvdB was supported by the NIH via grants NIMH U01MH119758 and U01MH101724 and the MRC via grant MR/T033045/1, MR/N022572/1 and MR/L011166/1. JV was supported by The SickKids Psychiatry Associates Chair in Developmental Psychopathology and NIMH U01MH119741-01. PMT was supported by the NIH via grants R01MH129742 and R01MH116147. CEB was supported by U54EB020403 from the Big Data to Knowledge (BD2K) Program, NIMH R01MH085953, NIMH U01MH101719. FVR receives research support from CIHR, Brain Canada, Michael Smith Foundation for Health Research, Vancouver Coastal Health Research Institute, and Weston Brain Institute for investigator-initiated research. Philanthropic support from Seedlings Foundation. In-kind equipment supports for this investigator-initiated trial from MagVenture. He has received honoraria for participation in an advisory board for Allergan. Publisher Copyright: © 2024 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.

PY - 2024/1/12

Y1 - 2024/1/12

N2 - 22q11.2 deletion syndrome (22q11DS) is the most frequently occurring microdeletion in humans. It is associated with a significant impact on brain structure, including prominent reductions in gray matter volume (GMV), and neuropsychiatric manifestations, including cognitive impairment and psychosis. It is unclear whether GMV alterations in 22q11DS occur according to distinct structural patterns. Then, 783 participants (470 with 22q11DS: 51% females, mean age [SD] 18.2 [9.2]; and 313 typically developing [TD] controls: 46% females, mean age 18.0 [8.6]) from 13 datasets were included in the present study. We segmented structural T1-weighted brain MRI scans and extracted GMV images, which were then utilized in a novel source-based morphometry (SBM) pipeline (SS-Detect) to generate structural brain patterns (SBPs) that capture co-varying GMV. We investigated the impact of the 22q11.2 deletion, deletion size, intelligence quotient, and psychosis on the SBPs. Seventeen GMV-SBPs were derived, which provided spatial patterns of GMV covariance associated with a quantitative metric (i.e., loading score) for analysis. Patterns of topographically widespread differences in GMV covariance, including the cerebellum, discriminated individuals with 22q11DS from healthy controls. The spatial extents of the SBPs that revealed disparities between individuals with 22q11DS and controls were consistent with the findings of the univariate voxel-based morphometry analysis. Larger deletion size was associated with significantly lower GMV in frontal and occipital SBPs; however, history of psychosis did not show a strong relationship with these covariance patterns. 22q11DS is associated with distinct structural abnormalities captured by topographical GMV covariance patterns that include the cerebellum. Findings indicate that structural anomalies in 22q11DS manifest in a nonrandom manner and in distinct covarying anatomical patterns, rather than a diffuse global process. These SBP abnormalities converge with previously reported cortical surface area abnormalities, suggesting disturbances of early neurodevelopment as the most likely underlying mechanism.

AB - 22q11.2 deletion syndrome (22q11DS) is the most frequently occurring microdeletion in humans. It is associated with a significant impact on brain structure, including prominent reductions in gray matter volume (GMV), and neuropsychiatric manifestations, including cognitive impairment and psychosis. It is unclear whether GMV alterations in 22q11DS occur according to distinct structural patterns. Then, 783 participants (470 with 22q11DS: 51% females, mean age [SD] 18.2 [9.2]; and 313 typically developing [TD] controls: 46% females, mean age 18.0 [8.6]) from 13 datasets were included in the present study. We segmented structural T1-weighted brain MRI scans and extracted GMV images, which were then utilized in a novel source-based morphometry (SBM) pipeline (SS-Detect) to generate structural brain patterns (SBPs) that capture co-varying GMV. We investigated the impact of the 22q11.2 deletion, deletion size, intelligence quotient, and psychosis on the SBPs. Seventeen GMV-SBPs were derived, which provided spatial patterns of GMV covariance associated with a quantitative metric (i.e., loading score) for analysis. Patterns of topographically widespread differences in GMV covariance, including the cerebellum, discriminated individuals with 22q11DS from healthy controls. The spatial extents of the SBPs that revealed disparities between individuals with 22q11DS and controls were consistent with the findings of the univariate voxel-based morphometry analysis. Larger deletion size was associated with significantly lower GMV in frontal and occipital SBPs; however, history of psychosis did not show a strong relationship with these covariance patterns. 22q11DS is associated with distinct structural abnormalities captured by topographical GMV covariance patterns that include the cerebellum. Findings indicate that structural anomalies in 22q11DS manifest in a nonrandom manner and in distinct covarying anatomical patterns, rather than a diffuse global process. These SBP abnormalities converge with previously reported cortical surface area abnormalities, suggesting disturbances of early neurodevelopment as the most likely underlying mechanism.

KW - 22q11 deletion syndrome

KW - gray matter volume

KW - magnetic resonnance imaging

KW - source-based morphometry

UR - https://www.scopus.com/pages/publications/85182249725

U2 - 10.1002/hbm.26553

DO - 10.1002/hbm.26553

M3 - Article

C2 - 38224541

AN - SCOPUS:85182249725

SN - 1065-9471

VL - 45

JO - Human Brain Mapping

JF - Human Brain Mapping

IS - 1

M1 - e26553

ER -

Source-based morphometry reveals structural brain pattern abnormalities in 22q11.2 deletion syndrome

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