Archival ReportCategorical Versus Dimensional Approaches to Autism-Associated Intermediate Phenotypes in 22q11.2 Microdeletion Syndrome

ABSTRACTBackgroundIndividuals with 22q11.2 microdeletion syndrome (22q11DS) have elevated rates of autism spectrum disorder (ASD), although the diagnosis is controversial. To determine whether there is a biological substrate of ASD in patients with 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.MethodsWe collected multiple neurocognitive measures and high-resolution T1-weighted magnetic resonance imaging scans from 116 individuals (29 patients who were 22q11DS-ASD+, 32 patients who were 22q11DS-ASD−, and 55 typically developing controls) who were between 6 and 26 years of age. Measures of subcortical volume, cortical thickness (CT), and surface area were extracted using the FreeSurfer image analysis software. 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 or neuroanatomic abnormalities observed in patients with 22q11DS-ASD+.ResultsIn comparison to 22q11DS-ASD- individuals, 22q11DS-ASD+ participants had decreased bilateral parahippocampal 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.ConclusionsA combination of categorical and dimensional measures of ASD may provide the most comprehensive understanding of ASDs in individuals with 22q11DS.