See the published version of this preprint at Molecular Autism.
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Research
Maria Gudbrandsen
Institute of Psychiatry Psychology and Neuroscience
Corresponding Author
ORCiD: https://orcid.org/0000-0002-0464-2065
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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
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CURRENT STATUS: Published
View the published article at Molecular Autism.
Version 3
Posted 26 May, 2020
No community comments so far
Editorial decision: Accept
On 28 May, 2020
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Received 28 May, 2020
Reviewer #1 agreed
On 20 May, 2020
Reviewers invited
Invitations sent on 18 May, 2020
Editor assigned
On 17 May, 2020
Submission checks complete
On 16 May, 2020
Editor invited
On 16 May, 2020
No comments provided
Reviewer #3 agreed
On 14 Apr, 2020
Review #3 received
Received 14 Apr, 2020
Editorial decision: Major revision
On 14 Apr, 2020
Review #2 received
Received 21 Mar, 2020
Review #1 received
Received 19 Mar, 2020
Reviewer #2 agreed
On 13 Mar, 2020
Reviewers invited
Invitations sent on 09 Mar, 2020
Reviewer #1 agreed
On 09 Mar, 2020
Editor assigned
On 09 Mar, 2020
Submission checks complete
On 08 Mar, 2020
Editor invited
On 08 Mar, 2020
No comments provided
Editorial decision: Major revision
On 30 Jan, 2020
Review #2 received
Received 12 Jan, 2020
Reviewer #5 agreed
On 09 Jan, 2020
Review #4 received
Received 06 Jan, 2020
Review #3 received
Received 06 Jan, 2020
Review #1 received
Received 28 Dec, 2019
Reviewer #4 agreed
On 17 Dec, 2019
Reviewer #3 agreed
On 15 Dec, 2019
Reviewers invited
Invitations sent on 12 Dec, 2019
Reviewer #1 agreed
On 12 Dec, 2019
Reviewer #2 agreed
On 12 Dec, 2019
Editor assigned
On 10 Dec, 2019
Submission checks complete
On 09 Dec, 2019
Editor invited
On 09 Dec, 2019
First submitted
On 06 Dec, 2019
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Subject Areas
Cellular & Molecular Neuroscience
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See the published version of this preprint at Molecular Autism.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Maria Gudbrandsen
Institute of Psychiatry Psychology and Neuroscience
Corresponding Author
ORCiD: https://orcid.org/0000-0002-0464-2065
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at Molecular Autism.
Version 3
Posted 26 May, 2020
No community comments so far
Editorial decision: Accept
On 28 May, 2020
Review #1 received
Received 28 May, 2020
Reviewer #1 agreed
On 20 May, 2020
Reviewers invited
Invitations sent on 18 May, 2020
Editor assigned
On 17 May, 2020
Submission checks complete
On 16 May, 2020
Editor invited
On 16 May, 2020
No comments provided
Reviewer #3 agreed
On 14 Apr, 2020
Review #3 received
Received 14 Apr, 2020
Editorial decision: Major revision
On 14 Apr, 2020
Review #2 received
Received 21 Mar, 2020
Review #1 received
Received 19 Mar, 2020
Reviewer #2 agreed
On 13 Mar, 2020
Reviewers invited
Invitations sent on 09 Mar, 2020
Reviewer #1 agreed
On 09 Mar, 2020
Editor assigned
On 09 Mar, 2020
Submission checks complete
On 08 Mar, 2020
Editor invited
On 08 Mar, 2020
No comments provided
Editorial decision: Major revision
On 30 Jan, 2020
Review #2 received
Received 12 Jan, 2020
Reviewer #5 agreed
On 09 Jan, 2020
Review #4 received
Received 06 Jan, 2020
Review #3 received
Received 06 Jan, 2020
Review #1 received
Received 28 Dec, 2019
Reviewer #4 agreed
On 17 Dec, 2019
Reviewer #3 agreed
On 15 Dec, 2019
Reviewers invited
Invitations sent on 12 Dec, 2019
Reviewer #1 agreed
On 12 Dec, 2019
Reviewer #2 agreed
On 12 Dec, 2019
Editor assigned
On 10 Dec, 2019
Submission checks complete
On 09 Dec, 2019
Editor invited
On 09 Dec, 2019
First submitted
On 06 Dec, 2019
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Cellular & Molecular Neuroscience
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Molecular Autism.
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.
Figure 1
Figure 2
Figure 3
This is a list of supplementary files associated with this preprint. Click to download.
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