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Categorical versus dimensional approaches to autism-associated intermediate phenotypes in 22q11.2 microdeletion syndrome.

ABSTRACT: BACKGROUND:22q11.2 Microdeletion syndrome (22q11DS) is associated with elevated rates of autism spectrum disorders (ASDs), although the diagnosis is controversial. In order to determine whether there is a biological substrate of ASD in 22q11DS, we examined neurocognitive and structural neuroanatomic differences between those with 22q11DS and an ASD diagnosis (22q11DS-ASD+) and those with 22q11DS without ASD (22q11DS-ASD-); we then determined whether these differences were better characterized within a categorical or dimensional framework. METHODS:We collected multiple neurocognitive measures and high-resolution T1-weighted scans on 116 individuals (29 22q11DS-ASD+, 32 22q11DS-ASD-, 55 typically developing controls) between 6 and 26 years of age. Measures of subcortical volume, cortical thickness (CT), and surface area were extracted using the FreeSurfer image analysis suite. Group differences in neurocognitive and neuroanatomic measures were assessed; regression analyses were then performed to determine whether a categorical or dimensional measure of ASD was a better predictor of neurocognitive impairment and/or neuroanatomic abnormalities observed in 22q11DS-ASD+. RESULTS:In comparison to 22q11DS-ASD-, 22q11DS-ASD+ participants exhibited decreased bilateral hippocampal CT and decreased right amygdala volumes. Those with 22q11DS-ASD+ also showed slowed processing speed and impairments in visuospatial and facial memory. Neurocognitive impairments fit a dimensional model of ASD, whereas reductions in parahippocampal CT were best explained by a categorical measure of ASD. CONCLUSIONS:A combination of categorical and dimensional measures of ASD may provide the most comprehensive understanding of ASDs in 22q11DS.

SUBMITTER: Jalbrzikowski M

PROVIDER: S-EPMC5373800 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Categorical versus dimensional approaches to autism-associated intermediate phenotypes in 22q11.2 microdeletion syndrome.

Jalbrzikowski Maria M Ahmed Khwaja Hamzah KH Patel Arati A Jonas Rachel R Kushan Leila L Chow Carolyn C Bearden Carrie E CE

Biological psychiatry. Cognitive neuroscience and neuroimaging 20170101 1

<h4>Background</h4>22q11.2 Microdeletion syndrome (22q11DS) is associated with elevated rates of autism spectrum disorders (ASDs), although the diagnosis is controversial. In order to determine whether there is a biological substrate of ASD in 22q11DS, we examined neurocognitive and structural neuroanatomic differences between those with 22q11DS and an ASD diagnosis (22q11DS-ASD+) and those with 22q11DS without ASD (22q11DS-ASD-); we then determined whether these differences were better characte ...[more]

PMID: 28367513

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Project description: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.

Dataset Information

Categorical versus dimensional approaches to autism-associated intermediate phenotypes in 22q11.2 microdeletion syndrome.

Publications

Categorical versus dimensional approaches to autism-associated intermediate phenotypes in 22q11.2 microdeletion syndrome.

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