In this study, TBV, GM, WM, and CC area were compared between 15 adolescents and young adults with ASD and 15 healthy control subjects, matched for gender and age. Our findings corroborate previous reports of an enlargement of TBV in adolescents and young adults with ASD (1
), especially in individuals with average and below average IQ (70–110). The current analyses suggest that increases in TBV are due to increases in both GM and WM. Given that subjects in our study were medication-naïve, the observed volume increases cannot be attributed to treatment effects (12
Our findings emphasize the strong impact of IQ differences on study outcomes. For example, positive correlations of IQ with TBV, GM, and WM were only observed in control but not in ASD individuals. Increased TBV, GM, and WM were predominantly observed in ASD individuals with IQ equal to or lower than the median IQ in our study. In a previous study on individuals with low-functioning autism (LFA), high-functioning autism (HFA), and Asperger syndrome (AS), only LFA and HFA subjects showed increased GM, whereas AS subjects did not show increased GM. Given that AS individuals showed significantly higher IQ scores than HFA in that study (13
), findings might have been driven by IQ differences between groups. Gray matter and WM increase might be due to an overproduction of neurons, glia, or astrocytes; abnormal myelination; and/or decreased neuronal elimination (pruning). In one study, active neuroinflammatory processes have been shown to exist in the WM, cortex, and cerebellum of patients with autism (14
). Neuropathological studies have reported abnormal neocortical minicolumns in 4- to 25-year-old individuals with ASD (15
), possibly resulting in increased GM and WM. Increased WM in our study showed a trend for an association with reduced dynamic balance and hand-finger imitation abilities across groups. A recent study reported a positive correlation of neurological subtle signs as indicators of motor impairment with local WM in the primary motor and premotor cortices of 8- to 12-year-old children with ASD (16
). Therefore, either local or global WM enlargement might contribute to motor and imitation impairment in ASD.
Corpus callosum area was smaller in ASD, likely due to individuals with high IQ and large WM. However, due to low sample size, the unadjusted post hoc comparison has to be viewed with caution. Reduced CC thickness was observed in the isthmus and anterior part of the splenium. Our findings are well in line with previous studies in age-, gender-, and IQ-matched samples (7
). The CC isthmus and anterior part of the splenium connect primary somatosensory, temporal, and posterior parietal fibers (17
). Several functional and structural MRI studies have reported volumetric changes and altered function of right and left temporal and parietal regions in ASD (7
). Reduction in CC thickness either might be the result of these structural and functional findings or might cause some of the functional differences between ASD and control individuals. Previous studies indicated CC hypoplasia, but not atrophy, and suggested a reduction in the number of axonal fibers traversing the CC (19
). A recent DTI study reported reduced CC fractional anisotropy and increased mean diffusivity in ASD individuals, also indicative of CC microstructure changes (10
Our study had several limitations. For example, the sample size was relatively small, so post hoc tests comparing ASD and control individuals with high/low IQ have to be viewed with caution and need to be replicated in a larger sample. Also, groups were not fully matched with regard to IQ measures. Similar to prior structural MRI studies, our study had a cross-sectional design, which does not allow conclusions about causality. Further structural MRI studies should implement a longitudinal approach to compare brain development in ASD and control children.
In conclusion, we replicated findings of increased TBV, GM, and WM in adolescent and adult ASD individuals and described the strong influence of IQ on these anatomical measures. Finally, CC area and posterior thickness were reduced, replicating previous studies.