Abnormal patterns of cortical gyrification in velo-cardio-facial syndrome (deletion 22q11.2): An MRI study
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Velo-cardio-facial syndrome (VCFS), also known as 22q11.2 deletion syndrome, is a common genetic condition associated with increased risk for developing schizophrenia. Given that cortical malformations play an integral role in the pattern of neuroanatomical alterations associated with VCFS, the aim of the present study was to quantify and localize gyral abnormalities. Magnetic resonance images were obtained on a 1.5 T scanner. The gyrification index (GI), a measure of the degree of cortical complexity, was differentially calculated for each lobe using a semi-automated protocol. The GI was calculated for 37 patients affected by VCFS as well as for 36 comparison individuals group-matched for age, handedness, and gender. The subjects affected by VCFS showed a significant decrease in the GI in the frontal and parietal lobes compared with the control group. The pattern of decreased gyrification in the frontal and parietal lobes further defines the structural changes associated with the syndrome and suggests underlying abnormalities in neural connectivity. Aberrant connectivity may be partially responsible for the cognitive and behavioral impairments in the syndrome, as well as the high incidence of schizophrenia among affected individuals.
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Imaging studies in 22q11.2 syndrome have revealed smaller brain volume, decreased cortical thickness in the superior parietal, right parietooccipital and inferior frontal gyrus, heterotopias and fewer gyri, and reduced volume in the hippocampus, cerebellum and amygdala, some of which varies based on the presence of schizophrenia or cognitive deficits.
“Imaging studies in 22q11.2 syndrome have revealed smaller brain volume [361], decreased cortical thickness in the superior parietal, right parietooccipital and inferior frontal gyrus, heterotopias and fewer gyri [27, 193, 314], and reduced volume in the hippocampus [84, 85], cerebellum [49] and amygdala [85], some of which varies based on the presence of schizophrenia or cognitive deficits [20, 31”
From Autism spectrum disorder: neuropathology and animal models (2017) · cites this paper as [314]
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“2DS patients implicate abnormal neuronal migration (14); imaging demonstrates related cortical anomalies including polymicrogyria and region-selective gray matter thinning (15, 16); and magnetic resonance spectroscopic studies show reduced GABA function (17).”
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Bearden, C. E., van Erp, T. G. M., Dutton, R. A., Lee, A. D., Simon, T. J., Cannon, T. D., Emanuel, B. S., McDonald‐McGinn, D. M., Zackai, E. H., & Thompson, P. M. (2008) · Cerebral Cortex · doi:10.1093/cercor/bhn064 · Cited by 82 · see citing works
“2DS (Schaer et al. 2006).”
Neuropathologic Features in Adults with 22q11.2 Deletion Syndrome
Kiehl, T. R., Chow, E. W. C., Mikulis, D. J., George, S. R., & Bassett, A. S. (2009) · Cerebral Cortex · doi:10.1093/cercor/bhn066 · Cited by 76 · see citing works
“Keywords: neuronal migration, pathology, schizophrenia, velocardiofacial syndrome”
BackgroundResultInfluentialGyral folding pattern analysis via surface profiling
Li, K., Guo, L., Li, G., Nie, J., Faraco, C., Cui, G., Zhao, Q. C., Miller, L. S., & Liu, T. (2010) · NeuroImage · doi:10.1016/j.neuroimage.2010.04.263 · Cited by 74 · see citing works
“Both of these two major stream approaches have generated many successful applications (Hardan et al., 2004;Schaer et al., 2006;Rettmann et al., 2006;Bonnici et al., 2007;Neal et al., 2007).”
Andersson, F., Glaser, B., Spiridon, M., Debbané, M., Vuilleumier, P. O., & D, S. E. M. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2007.02.022 · Cited by 73 · see citing works
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“Schaer et al. (2006) investigated individuals with the 22q11.”
Meechan, D. W., Maynard, T. M., Tucker, E. S., & LaMantia, A. (2010) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2010.08.005 · Cited by 66 · see citing works
“…cortex in individuals with a variety of developmental disorders—including areal differences in cortical thickness polymicrogyria, and periventricular heterotopias—are also seen in 22q11DS patients (Bearden et al., 2007, 2009; Kiehl et al., 2009; Schaer et al., 2006; van Amelsvoort et al., 2004).”
BackgroundAberrant Cortical Morphometry in the 22q11.2 Deletion Syndrome
Schmitt, J. E., Vandekar, S., Yi, J. J., Calkins, M. E., Ruparel, K., Roalf, D. R., Whinna, D. A., Souders, M. C., Satterthwaite, T. D., Prabhakaran, K., et al. (2014) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.10.025 · Cited by 66 · see citing works
“More recent studies have explored newer measures of cerebral morphometry such as cortical thickness (14–17), cerebral surface area (16), and measures of gyral complexity (18,19).”
Mancini, V., Sandini, C., Padula, M. C., Zöller, D., Schneider, M., Schaer, M., & D, S. E. M. (2019) · Molecular Psychiatry · doi:10.1038/s41380-019-0443-z · Cited by 66 · see citing works
“Brain abnormalities are also a common feature of the syndrome, as patients have an average 11% total brain volume decrease [44] and reduced gyrification in the frontal and parietal lobes [45].”
BackgroundSelf-citationA computational model of cerebral cortex folding
Nie, J., Guo, L., Li, G., Faraco, C., Miller, L. S., & Liu, T. (2010) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2010.02.002 · Cited by 64 · see citing works
Congenital heart disease affects local gyrification in 22q11.2 deletion syndrome
Schaer, M., Glaser, B., Cuadra, M. B., Debbané, M., Thiran, J., & D, S. E. M. (2009) · Developmental Medicine & Child Neurology · doi:10.1111/j.1469-8749.2009.03281.x · Cited by 57 · see citing works
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“2DS, there have been radiological and pathological reports of cortical dysgenesis and abnormal gyrification patterns in some patients (Kiehl et al., 2009; Robin et al., 2006; Schaer et al., 2006; Sztriha et al., 2004).”
BackgroundMeechan, D. W., Rutz, H. L. H., Fralish, M. S., Maynard, T. M., Rothblat, L. A., & LaMantia, A. (2013) · Cerebral Cortex · doi:10.1093/cercor/bht308 · Cited by 50 · see citing works
Mathematical disabilities in children with velo-cardio-facial syndrome
Smedt, B. D., Swillen, A., Devriendt, K., Fryns, J. P., Verschaffel, L., & Ghesquière, P. (2006) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2006.08.024 · Cited by 50 · see citing works
Evidence of gray matter reduction and dysfunction in chromosome 22q11.2 deletion syndrome
Shashi, V., Kwapil, T. R., Kaczorowski, J. A., Berry, M. N., Santos, C. S., Howard, T. D., Goradia, D. D., Prasad, K. M. R., Vaibhav, D., Rajarethinam, R., et al. (2009) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2009.07.003 · Cited by 47 · see citing works
“, 2005) and decreased gyrification in the frontal lobes [this study included both children and adults with 22q11DS] (Schaer et al., 2006).”
BackgroundThe Heritability of Cortical Folding: Evidence from the Human Connectome Project
Schmitt, J. E., Raznahan, A., Liu, S., & Neale, M. C. (2020) · Cerebral Cortex · doi:10.1093/cercor/bhaa254 · Cited by 43 · see citing works
Dufour, F., Schaer, M., Debbané, M., Farhoumand, R., Glaser, B., & D, S. E. M. (2008) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2008.06.012 · Cited by 45 · see citing works
“Image optimization was performed in Brain- Image 5.2 following standard procedures whose details have been published elsewhere (Reiss et al., 1998; Schaer et al., 2006).”
InfluentialSelf-citationDocherty, A. R., Hagler, D. J., Panizzon, M. S., Neale, M. C., Eyler, L. T., Fennema‐Notestine, C., Franz, C. E., Jak, A. J., Lyons, M. J., Rinker, D. A., et al. (2014) · NeuroImage · doi:10.1016/j.neuroimage.2014.11.040 · Cited by 41 · see citing works
Germanaud, D., Lefèvre, J., Fischer, C., Bintner, M., Curie, A., Portes, V. D., D, S. E. M., Elmaleh, M., Lamblin, D., Passemard, S., et al. (2014) · NeuroImage · doi:10.1016/j.neuroimage.2014.07.057 · Cited by 40 · see citing works
“2 deletion syndrome, with gyrification index (Schaer et al., 2006, 2008), combinedwith fractal indices inWilliams syndrome (Gaser et al., 2006; Schmitt et al., 2002; Thompson et al., 2005), or in schizophrenia with sulci shape analysis (Cachia et al., 2008; Plaze et al., 2011).”
BackgroundSelf-citationLukoshe, A., Hokken‐Koelega, A. C. S., van der Lugt, A., & White, T. J. H. (2014) · PLoS ONE · doi:10.1371/journal.pone.0107320 · Cited by 37 · see citing works
“In contrast, low gyrification has been associated with mental retardation [20], dyslexia [21], early-onset schizophrenia [22] and velo-cardio-facial syndrome [23], although in the latter increased gyrification was reported as well [24].”
BackgroundRegional Alterations in Cortical Sulcal Depth in Living Fetuses with Down Syndrome
Yun, H. J., Perez, J. D. R., Sosa, P., Valdés, J. A., Madan, N., Kitano, R., Akiyama, S., Skotko, B. G., Feldman, H. A., Bianchi, D. W., et al. (2021) · Cerebral Cortex · doi:10.1093/cercor/bhaa255 · Cited by 33 · see citing works
“The definition of GI is the area ratio between the cortical surface and the convex hull (Zilles et al. 1988; Harris et al. 2004; Gaser et al. 2006; Schaer et al. 2006).”
Palomo, T., Beninger, R., Kostrzewa, R., & Archer, T. (2008) · Neurotoxicity research · doi:10.1007/bf03033572 · Cited by 29 · see citing works
“Verhoeven and Tunier (2008) discuss the search for candidate genes, e.g., DISC1 (Ekelund et al., 2001; Hwu et al., 2003; Sachs et al., 2005) and the 22q11 deletion syndrome (Shprintzen et al., 1978; Shprintzen, 2000; Schaer et al., 2006; Williams et al., 2007).”
BackgroundKim, E.-H., Yum, M., Lee, B. H., Kim, H., Lee, H.-J., Kim, G.-H., Lee, Y. J., Yoo, H., & Ko, T. (2016) · Journal of Clinical Neurology · doi:10.3988/jcn.2016.12.1.85 · Cited by 33 · see citing works
Schaer, M., & D, S. E. M. (2007) · Child and Adolescent Psychiatric Clinics of North America · doi:10.1016/j.chc.2007.02.002 · Cited by 33 · see citing works
Self-citationIncidental Radiologic Findings in the 22q11.2 Deletion Syndrome
Schmitt, J. E., Yi, J. J., Roalf, D. R., Loevner, L. A., Ruparel, K., Whinna, D. A., Souders, M. C., McDonald‐McGinn, D. M., Yodh, E., Vandekar, S., et al. (2014) · American Journal of Neuroradiology · doi:10.3174/ajnr.a4003 · Cited by 28 · see citing works
Facial emotion perception by intensity in children and adolescents with 22q11.2 deletion syndrome
Leleu, A., Saucourt, G., Rigard, C., Chesnoy, G., Baudouin, J., Rossi, M., Edery, P., Nicolas Franck, B., & Demily, C. (2015) · European Child & Adolescent Psychiatry · doi:10.1007/s00787-015-0741-1 · Cited by 28 · see citing works
Glaser, B., Schaer, M., Berney, S., Debbané, M., Vuilleumier, P. O., & D, S. E. M. (2007) · Schizophrenia Research · doi:10.1016/j.schres.2007.08.016 · Cited by 28 · see citing works
“5 Tscanner, details on the sequence parameters and pre-processing have been previously described (Debbane et al., 2006b; Eliez et al., 2001b; Schaer et al., 2006).”
Self-citationEisenberg, D. P., Jabbi, M., & Berman, K. F. (2010) · NeuroImage · doi:10.1016/j.neuroimage.2010.02.070 · Cited by 27 · see citing works
Cortical gyrification in velo-cardio-facial (22q11.2 deletion) syndrome: A longitudinal study
Kunwar, A., Ramanathan, S., Nelson, J., Antshel, K. M., Fremont, W. P., Higgins, A. M., Shprintzen, R. J., & Kates, W. R. (2012) · Schizophrenia Research · doi:10.1016/j.schres.2012.01.032 · Cited by 27 · see citing works
Zeng, T., Chen, H., Fakhry, A., Hu, X. P., Liu, T., & Ji, S. (2014) · Brain Structure and Function · doi:10.1007/s00429-014-0821-x · Cited by 26 · see citing works
“In human brain mapping, the shape characteristics of cortical gyri and sulci have been extensively examined (Neal et al. 2007; Schaer et al. 2006; Rettmann et al. 2006; Hardan et al. 2004; Bonnici et al. 2007) in both healthy and diseased brains.”
BackgroundSrivastava, S., Buonocore, M. H., & Simon, T. J. (2011) · Human Brain Mapping · doi:10.1002/hbm.21206 · Cited by 26 · see citing works
“Local gyrification index (lGI; Schaer et al. [2008]: IEEE Trans Med Imaging 27:161–170) was used to characterize the cortical gyrification at each vertex of the pial surface.”
MethodLepach, A. C., & Petermann, F. (2011) · Neurocase · doi:10.1080/13554794.2010.536954 · Cited by 25 · see citing works
“Decreased gyrification in the frontal and parietal lobes suggests underlying abnormalities in neural connectivity (Schaer et al., 2006).”
BackgroundComprehensive neurocognitive endophenotyping strategies for mouse models of genetic disorders
Hunsaker, M. R. (2012) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2011.12.001 · Cited by 25 · see citing works
Mapping Cortical Morphology in Youth With Velocardiofacial (22q11.2 Deletion) Syndrome
Kates, W. R., Bansal, R., Fremont, W. P., Antshel, K. M., Hao, X., Higgins, A. M., Liu, J., Shprintzen, R. J., & Peterson, B. S. (2011) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2010.12.002 · Cited by 23 · see citing works
Yun, H. J., Chung, A. W., Vasung, L., Yang, E., Tarui, T., Rollins, C. K., Ortinau, C. M., Grant, P. E., & Im, K. (2018) · NeuroImage · doi:10.1016/j.neuroimage.2018.12.023 · Cited by 21 · see citing works
“We quantify the folding complexity using the Gyrification Index (GI), which is defined as the areal ratio between the cortical surface and the external convex hull (Gaser et al., 2006; Harris et al., 2004; Schaer et al., 2006; Zilles et al., 1988).”
Antshel, K. M., & Shprintzen, R. J. (2010) · doi:10.1093/oso/9780195342680.003.0030 · Cited by 20 · see citing works
Liu, B., Zhang, X., Bakken, L. R., Snipen, L. G., & Frostegård, Å. (2019) · Frontiers in Microbiology · doi:10.3389/fmicb.2018.03208 · Cited by 19 · see citing works
Padula, M. C., Schaer, M., Armando, M., Sandini, C., Zöller, D., Scariati, E., Schneider, M., & D, S. E. M. (2018) · Psychological Medicine · doi:10.1017/s0033291717003920 · Cited by 18 · see citing works
Self-citationMous, S. E., Karatekin, C., Kao, C.-Y., Gottesman, I. I., Danielle Posthuma, B., & White, T. J. H. (2013) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2013.12.002 · Cited by 17 · see citing works
“The most consistent findings in VCFS are decreased gyrification in the frontal and parietal lobes (Schaer et al., 2006; Kunwar et al., 2012; Srivastava et al., 2012) and decreased gyrification in occipital and midline regions of the brain (Srivastava et al.”
BackgroundResultDisrupted fornix integrity in children with chromosome 22q11.2 deletion syndrome
Deng, Y., Goodrich‐Hunsaker, N. J., Cabaral, M. H., Amaral, D. G., Buonocore, M. H., Harvey, D. J., Kalish, K., Carmichael, O. T., Schumann, C. M., Lee, A., et al. (2015) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2015.02.002 · Cited by 16 · see citing works
“…Campbell et al., 2006; Machado et al., 2007; Beaton et al., 2010), reduced cortical thickness (Bearden et al., 2007, 2009) and gyral complexity (Schaer et al., 2006, 2009; Srivastava et al., 2011); altered connectivity in major white matter fiber tracts (Simon et al., 2005c; Machado et al.,…”
BackgroundWhite matter microstructural deficits in 22q11.2 deletion syndrome
Roalf, D., Schmitt, J. E., Vandekar, S., Satterthwaite, T., Shinohara, R., Ruparel, K., Elliott, M., Prabhakaran, K., McDonald-McGinn, D., Zackai, E., et al. (2017) · Psychiatry research. Neuroimaging · doi:10.1016/j.pscychresns.2017.08.001 · Cited by 17 · see citing works
“Indeed, both 22q11DS and idiopathic schizophrenia share brain morphological changes (Eliez et al., 2001, 2000; Glahn et al., 2008; Jalbrzikowski et al., 2013; Schaer et al., 2006), including alterations in WM structure and organization (Asami et al.”
BackgroundVáša, F., Griffa, A., Scariati, E., Schaer, M., Urben, S., Eliez, S., & Hagmann, P. (2015) · NeuroImage Clinical · doi:10.1016/j.nicl.2015.11.017 · Cited by 13 · see citing works
“2 microdeletion has become an established genetic model for schizophrenia spectrum disorders. ment of Psychiatry, Sir William ted Kingdom. t work.”
InfluentialSelf-citationTop-down or bottom-up: Contrasting perspectives on psychiatric diagnoses
Verhoeven, W. M. A., Egger, J. I. M., Gunning, W. B., M.Bevers, & de Pont, B. J. H. B. (2008) · Biologics · doi:10.2147/btt.s3053 · Cited by 13 · see citing works
“Magnetic resonance imaging has demonstrated wide spread defi cits in white matter and reduced brain volumes (Van Amelsfoort et al 2004; Schaer et al 2006).”
Genomic and Imaging Biomarkers in Schizophrenia
Reddaway, J., Doherty, J. L., Lancaster, T. M., Linden, D. E. J., Walters, J., & Hall, J. (2018) · Current topics in behavioral neurosciences · doi:10.1007/7854_2018_52 · Cited by 10 · see citing works
Mechanism Exploration of 3-Hinge Gyral Formation and Pattern Recognition
Razavi, M. J., Liu, T., & Wang, X. (2021) · Cerebral Cortex Communications · doi:10.1093/texcom/tgab044 · Cited by 10 · see citing works
Quantifying indices of short- and long-range white matter connectivity at each cortical vertex
Padula, M. C., Schaer, M., Scariati, E., Mutlu, A. K., Zöller, D., Schneider, M., & D, S. E. M. (2017) · PLoS ONE · doi:10.1371/journal.pone.0187493 · Cited by 8 · see citing works
Self-citationClinical perspectives on the genetics of schizophrenia: A bottom-up orientation
Verhoeven, W. M. A., & Tuinier, S. (2008) · Neurotoxicity Research · doi:10.1007/bf03033806 · Cited by 7 · see citing works
Schneider, M., & D, S. E. M. (2009) · Archives de Pédiatrie · doi:10.1016/j.arcped.2009.10.010 · Cited by 5 · see citing works
A Computational Model of Cerebral Cortex Folding
Nie, J., Li, G., Guo, L., & Liu, T. (2009) · Lecture notes in computer science · doi:10.1007/978-3-642-04271-3_56 · Cited by 5 · see citing works
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Neurologic Complications of Congenital Heart Disease and Cardiac Surgery in Children
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“Our observation that 22qDS youth show hypogyrification in the medial prefrontal and lateral orbitofrontal cortex is consistent with previous hypogyrification findings in the medial frontal and parietal cortex (Schaer et al., 2006; Schmitt et al., 2015; Srivastava et al., 2011).”
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Structural brain changes in adolescents at risk for psychosis
Weusten, J. (2010) · Utrecht University Repository (Utrecht University)
DEFICITS IN EYE MOVEMENT CONTROL IN CHILDREN DIAGNOSED WITH 22Q11.2 DELETION SYNDROME.
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“[14] On tests of general intellectual functioning, the verbal intelligence quotient (IQ) exceeds performance IQ in the children with VCFS.[16,19] These variations in IQ reflect the problems in planning capability, visuospatial capacity, and concept construction. braIn structural anomalIes Although the biological deter…”
BackgroundInfluentialNeurological Complications of Congenital Heart Disease and Cardiac Surgery in Children
Limperopoulos, C., & du Plessis, A. J. (2008) · Elsevier eBooks · doi:10.1016/b978-044306707-5.50007-9
Congenital, developmental, and other childhood-onset disorders
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Mechanics of cortical folding in a developing brain
Aghjeh, R., & Jalil, M. (2018)
Congenital, developmental and other childhood-onset disorders
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“2 syndrome, volume reduction in gray and white matter has been reported, particularly in the parietal lobe [38].”
- Authors
- Schaer, M., Eric Schmitt, J., Glaser, B., Lazeyras, F., Delavelle, J., & Eliez, S.
- Affiliations
- University of Geneva (CH)
- University Hospital of Geneva (CH)
- Venue
- Psychiatry Research: Neuroimaging
- Publisher
- Elsevier BV
- Published
- 2006-01
- Volume
- 146
- Issue
- 1
- Pages
- 1-11
- ISSN
- 0925-4927 (ISSN-L)
- OpenAlex
- W2044618620
- Cited by
- 76
- References
- 79
- Citations by year
- 2025: 1 · 2023: 1 · 2021: 1 · 2020: 3 · 2019: 3 · 2018: 4 · 2017: 4 · 2016: 2 · 2015: 4 · 2014: 8 · 2013: 4 · 2012: 4
- FWCI
- 4.92
- Type
- journal article
- Language
- en
- Open access
- green
- infoscience.epfl.ch
- Locations
- Psychiatry Research Neuroimaging (publishedVersion)
- PubMed (publishedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Funders
- National Alliance for Research on Schizophrenia and Depression
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Fetal and Pediatric Neurological Disorders
- Keywords
- 22q11.2 deletion syndrome, cortical gyrification, gyrification index, malformations of cortical development, frontal lobe, parietal lobe, schizophrenia risk, neuronal connectivity, brain structure
- MeSH terms
- Adolescent, Adult, Cerebral Cortex, Chromosome Deletion, Chromosomes, Human, Pair 22, DiGeorge Syndrome, Female, Humans, Intelligence, Intelligence Tests, Magnetic Resonance Imaging, Male, Schizophrenia
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