Neuroanatomical differences in toddler boys with fragile x syndrome and idiopathic autism.

CONTEXT: Autism is an etiologically heterogeneous neurodevelopmental disorder for which there is no known unifying etiology or pathogenesis. Many conditions of atypical development can lead to autism, including fragile X syndrome (FXS), which is presently the most common known single-gene cause of autism.

OBJECTIVE: To examine whole-brain morphometric patterns that discriminate young boys with FXS from those with idiopathic autism (iAUT) as well as control participants.

DESIGN: Cross-sectional, in vivo neuroimaging study.

SETTING: Academic medical centers.

PATIENTS: Young boys (n = 165; aged 1.57-4.15 years) diagnosed as having FXS or iAUT as well as typically developing and idiopathic developmentally delayed controls.

MAIN OUTCOME MEASURES: Univariate voxel-based morphometric analyses, voxel-based morphometric multivariate pattern classification (linear support vector machine), and clustering analyses (self-organizing map).

RESULTS: We found that frontal and temporal gray and white matter regions often implicated in social cognition, including the medial prefrontal cortex, orbitofrontal cortex, superior temporal region, temporal pole, amygdala, insula, and dorsal cingulum, were aberrant in FXS and iAUT as compared with controls. However, these differences were in opposite directions for FXS and iAUT relative to controls; in general, greater volume was seen in iAUT compared with controls, who in turn had greater volume than FXS. Multivariate analysis showed that the overall pattern of brain structure in iAUT generally resembled that of the controls more than FXS, both with and without AUT.

CONCLUSIONS: Our findings demonstrate that FXS and iAUT are associated with distinct neuroanatomical patterns, further underscoring the neurobiological heterogeneity of iAUT.