Abstract

BackgroundA 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.MethodsWe 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.ResultsThe 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.LimitationsWe 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).ConclusionsOur findings indicate that neuroanatomical correlates of ASD symptomatology in carriers of the 22q11.2 microdeletion diverge from those in idiopathic ASD.

Highlights

  • 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

  • We found a significant effect of group for total brain volume (F(3) = 10.56, p < 0.001) and total surface area (SA) (F(3) = 12.41, p < 0.001), with both 22q11.2DS groups having a significantly lower total volume and area compared to both idiopathic ASD and typically developing (TD) controls (p < 0.05 for all pair-wise comparisons)

  • There was a significant effect of group for mean cortical thickness (CT) (F(3) = 3.74, p < 0.05) across the cortex, with idiopathic ASD individuals having a trend towards reduced CT compared to 22q11.nonASD individuals (p = 0.088), while no other pair-wise comparison was significant

Read more

Summary

Objectives

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. This study aimed to examine the neuroanatomical underpinnings of ASD symptomatology across disorders using a categorical approach that allowed us to establish the extent to which 22q11.2DS modulates the neuroanatomy of ASD. In a second analysis step, we aimed to consolidate the results of the categorical approach, where ASD is treated as a “fixed-effect” variable based on diagnostic labels, with a multivariate dimensional approach using canonical correlation analysis (CCA), where ASD is considered a complex clinical construct or phenotypic trait spanned by multiple symptom domains across disorders. This study aimed to determine whether ASD symptomatology in individuals with 22q11.2DS is underpinned by similar neuroanatomical substrates that mediate ASD symptoms in non22q11.2DS

Methods
Results
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call