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.
Keywords: amygdala; cortical thickness; dimensional measures; parahippocampus; social behavior; velocardiofacial syndrome.