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Neuroanatomical underpinnings of autism symptomatology in carriers and non-carriers of the 22q11.2 microdeletion

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Neuroanatomical underpinnings of autism symptomatology in carriers and non-carriers of the 22q11.2 microdeletion. / Gudbrandsen, Maria; Bletsch, Anke; Mann, Caroline et al.

In: Molecular Autism, Vol. 11, No. 1, 46, 08.06.2020, p. 46.

Research output: Contribution to journalArticlepeer-review

Harvard

Gudbrandsen, M, Bletsch, A, Mann, C, Daly, E, Murphy, CM, Stoencheva, V, Blackmore, CE, Rogdaki, M, Kushan, L, Bearden, CE, Murphy, DGM, Craig, MC & Ecker, C 2020, 'Neuroanatomical underpinnings of autism symptomatology in carriers and non-carriers of the 22q11.2 microdeletion', Molecular Autism, vol. 11, no. 1, 46, pp. 46. https://doi.org/10.1186/s13229-020-00356-z

APA

Gudbrandsen, M., Bletsch, A., Mann, C., Daly, E., Murphy, C. M., Stoencheva, V., Blackmore, C. E., Rogdaki, M., Kushan, L., Bearden, C. E., Murphy, D. G. M., Craig, M. C., & Ecker, C. (2020). Neuroanatomical underpinnings of autism symptomatology in carriers and non-carriers of the 22q11.2 microdeletion. Molecular Autism, 11(1), 46. [46]. https://doi.org/10.1186/s13229-020-00356-z

Vancouver

Gudbrandsen M, Bletsch A, Mann C, Daly E, Murphy CM, Stoencheva V et al. Neuroanatomical underpinnings of autism symptomatology in carriers and non-carriers of the 22q11.2 microdeletion. Molecular Autism. 2020 Jun 8;11(1):46. 46. https://doi.org/10.1186/s13229-020-00356-z

Author

Gudbrandsen, Maria ; Bletsch, Anke ; Mann, Caroline et al. / Neuroanatomical underpinnings of autism symptomatology in carriers and non-carriers of the 22q11.2 microdeletion. In: Molecular Autism. 2020 ; Vol. 11, No. 1. pp. 46.

Bibtex Download

@article{06b4e4eff03f4038a9450361cab93ef6,
title = "Neuroanatomical underpinnings of autism symptomatology in carriers and non-carriers of the 22q11.2 microdeletion",
abstract = "BACKGROUND: A crucial step to understanding the mechanistic underpinnings of autism spectrum disorder (ASD), is to examine if the biological underpinnings of ASD in genetic high-risk conditions, like 22q11.2 deletion syndrome (22q11.2DS), are similar to those in idiopathic illness. This study aimed to examine if ASD symptomatology in 22q11.2DS is underpinned by the same-or distinct-neural systems that mediate these symptoms in non-deletion carriers. METHODS: We examined vertex-wise estimates of cortical volume (CV), surface area (SA), and cortical thickness across 131 individuals between 6 and 25 years of age including (1) 50 individuals with 22q11.2DS, out of which n = 25 had a diagnosis of ASD, (2) 40 non-carriers of the microdeletion with a diagnosis of ASD (i.e., idiopathic ASD), and (3) 41 typically developing (TD) controls. We employed a 2-by-2 factorial design to identify neuroanatomical variability associated with the main effects of 22q11.2DS and ASD, as well as their interaction. Further, using canonical correlation analysis (CCA), we compared neuroanatomical variability associated with the complex (i.e., multivariate) clinical phenotype of ASD between 22q11.2 deletion carriers and non-carriers. RESULTS: The set of brain regions associated with the main effect of 22q11.2DS was distinct from the neuroanatomical underpinnings of the main effect of ASD. Moreover, significant 22q11.2DS-by-ASD interactions were observed for CV and SA in the dorsolateral prefrontal cortex, precentral gyrus, and posterior cingulate cortex, suggesting that the neuroanatomy of ASD is significantly modulated by 22q11.2DS (p < 0.01). We further established that the multivariate patterns of neuroanatomical variability associated with differences in symptom profiles significantly differed between 22q11.2 deletion carriers and non-carriers. LIMITATIONS: We employed a multicenter design to overcome single-site recruitment limitations; however, FreeSurfer-derived measures of surface anatomy have been shown to be highly reliable across scanner platforms and field strengths. Further, we controlled for gender to address the differing distribution between idiopathic ASD individuals and the other groups. Nonetheless, the gender distribution in our sample reflects that of the respective populations, adding to the generalizability of our results. Last, we included individuals with a relatively wide age range (i.e., 6-25 years). CONCLUSIONS: Our findings indicate that neuroanatomical correlates of ASD symptomatology in carriers of the 22q11.2 microdeletion diverge from those in idiopathic ASD.",
keywords = "22q11.2 deletion syndrome, Autism spectrum disorder, Brain anatomy, Neurodevelopment, Surface-based anatomy",
author = "Maria Gudbrandsen and Anke Bletsch and Caroline Mann and Eileen Daly and Murphy, {Clodagh M} and Vladimira Stoencheva and Blackmore, {Charlotte E} and Maria Rogdaki and Leila Kushan and Bearden, {Carrie E} and Murphy, {Declan G M} and Craig, {Michael C} and Christine Ecker",
year = "2020",
month = jun,
day = "8",
doi = "10.1186/s13229-020-00356-z",
language = "English",
volume = "11",
pages = "46",
journal = "Molecular Autism",
issn = "2040-2392",
publisher = "BioMed Central",
number = "1",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - Neuroanatomical underpinnings of autism symptomatology in carriers and non-carriers of the 22q11.2 microdeletion

AU - Gudbrandsen, Maria

AU - Bletsch, Anke

AU - Mann, Caroline

AU - Daly, Eileen

AU - Murphy, Clodagh M

AU - Stoencheva, Vladimira

AU - Blackmore, Charlotte E

AU - Rogdaki, Maria

AU - Kushan, Leila

AU - Bearden, Carrie E

AU - Murphy, Declan G M

AU - Craig, Michael C

AU - Ecker, Christine

PY - 2020/6/8

Y1 - 2020/6/8

N2 - BACKGROUND: A crucial step to understanding the mechanistic underpinnings of autism spectrum disorder (ASD), is to examine if the biological underpinnings of ASD in genetic high-risk conditions, like 22q11.2 deletion syndrome (22q11.2DS), are similar to those in idiopathic illness. This study aimed to examine if ASD symptomatology in 22q11.2DS is underpinned by the same-or distinct-neural systems that mediate these symptoms in non-deletion carriers. METHODS: We examined vertex-wise estimates of cortical volume (CV), surface area (SA), and cortical thickness across 131 individuals between 6 and 25 years of age including (1) 50 individuals with 22q11.2DS, out of which n = 25 had a diagnosis of ASD, (2) 40 non-carriers of the microdeletion with a diagnosis of ASD (i.e., idiopathic ASD), and (3) 41 typically developing (TD) controls. We employed a 2-by-2 factorial design to identify neuroanatomical variability associated with the main effects of 22q11.2DS and ASD, as well as their interaction. Further, using canonical correlation analysis (CCA), we compared neuroanatomical variability associated with the complex (i.e., multivariate) clinical phenotype of ASD between 22q11.2 deletion carriers and non-carriers. RESULTS: The set of brain regions associated with the main effect of 22q11.2DS was distinct from the neuroanatomical underpinnings of the main effect of ASD. Moreover, significant 22q11.2DS-by-ASD interactions were observed for CV and SA in the dorsolateral prefrontal cortex, precentral gyrus, and posterior cingulate cortex, suggesting that the neuroanatomy of ASD is significantly modulated by 22q11.2DS (p < 0.01). We further established that the multivariate patterns of neuroanatomical variability associated with differences in symptom profiles significantly differed between 22q11.2 deletion carriers and non-carriers. LIMITATIONS: We employed a multicenter design to overcome single-site recruitment limitations; however, FreeSurfer-derived measures of surface anatomy have been shown to be highly reliable across scanner platforms and field strengths. Further, we controlled for gender to address the differing distribution between idiopathic ASD individuals and the other groups. Nonetheless, the gender distribution in our sample reflects that of the respective populations, adding to the generalizability of our results. Last, we included individuals with a relatively wide age range (i.e., 6-25 years). CONCLUSIONS: Our findings indicate that neuroanatomical correlates of ASD symptomatology in carriers of the 22q11.2 microdeletion diverge from those in idiopathic ASD.

AB - BACKGROUND: A crucial step to understanding the mechanistic underpinnings of autism spectrum disorder (ASD), is to examine if the biological underpinnings of ASD in genetic high-risk conditions, like 22q11.2 deletion syndrome (22q11.2DS), are similar to those in idiopathic illness. This study aimed to examine if ASD symptomatology in 22q11.2DS is underpinned by the same-or distinct-neural systems that mediate these symptoms in non-deletion carriers. METHODS: We examined vertex-wise estimates of cortical volume (CV), surface area (SA), and cortical thickness across 131 individuals between 6 and 25 years of age including (1) 50 individuals with 22q11.2DS, out of which n = 25 had a diagnosis of ASD, (2) 40 non-carriers of the microdeletion with a diagnosis of ASD (i.e., idiopathic ASD), and (3) 41 typically developing (TD) controls. We employed a 2-by-2 factorial design to identify neuroanatomical variability associated with the main effects of 22q11.2DS and ASD, as well as their interaction. Further, using canonical correlation analysis (CCA), we compared neuroanatomical variability associated with the complex (i.e., multivariate) clinical phenotype of ASD between 22q11.2 deletion carriers and non-carriers. RESULTS: The set of brain regions associated with the main effect of 22q11.2DS was distinct from the neuroanatomical underpinnings of the main effect of ASD. Moreover, significant 22q11.2DS-by-ASD interactions were observed for CV and SA in the dorsolateral prefrontal cortex, precentral gyrus, and posterior cingulate cortex, suggesting that the neuroanatomy of ASD is significantly modulated by 22q11.2DS (p < 0.01). We further established that the multivariate patterns of neuroanatomical variability associated with differences in symptom profiles significantly differed between 22q11.2 deletion carriers and non-carriers. LIMITATIONS: We employed a multicenter design to overcome single-site recruitment limitations; however, FreeSurfer-derived measures of surface anatomy have been shown to be highly reliable across scanner platforms and field strengths. Further, we controlled for gender to address the differing distribution between idiopathic ASD individuals and the other groups. Nonetheless, the gender distribution in our sample reflects that of the respective populations, adding to the generalizability of our results. Last, we included individuals with a relatively wide age range (i.e., 6-25 years). CONCLUSIONS: Our findings indicate that neuroanatomical correlates of ASD symptomatology in carriers of the 22q11.2 microdeletion diverge from those in idiopathic ASD.

KW - 22q11.2 deletion syndrome

KW - Autism spectrum disorder

KW - Brain anatomy

KW - Neurodevelopment

KW - Surface-based anatomy

UR - http://www.scopus.com/inward/record.url?scp=85086297170&partnerID=8YFLogxK

U2 - 10.1186/s13229-020-00356-z

DO - 10.1186/s13229-020-00356-z

M3 - Article

C2 - 32513259

VL - 11

SP - 46

JO - Molecular Autism

JF - Molecular Autism

SN - 2040-2392

IS - 1

M1 - 46

ER -

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