| Objective. The prevalence of macrocephaly (head circumference >97th percentile) is approximately seven fold greater in autistic individuals compared to controls. In this study, frontal lobe morphology was examined in macrocephalic autistic, normocephalic autistic, typically developing, and benign macrocephalic subjects. The following three questions were addressed. (1) Do macrocephalic autistic subjects, normocephalic autistic, benign macrocephalic, and typically developing subjects exhibit differences in frontal lobe volume after controlling for age, intelligence, and head size? (2) Do macrocephalic and normocephalic subjects show similar patterns of frontal lobe development? (3) Do autistic subjects, irrespective of head size classification, show distinct patterns of frontal lobe development compared to controls? Method. Male autistic subjects ages 7-31 years were diagnosed using the Autism Diagnostic Interview-Revised and the Autism Diagnostic Observation Schedule-Generic. Multispectral brain image analysis was carried out for frontal gray and white matter volumes. Results. There were no volumetric differences between the four groups on measures of frontal gray matter, frontal white matter, or total frontal volume after controlling for age, intelligence, and head size. Within the autistic and control groups, the relationships between age and gray matter, white matter, and total frontal volumes were similar for macrocephalic and normocephalic subjects. When macrocephalic and normocephalic subjects were combined into autistic and control groups, age-frontal morphology regression analyses showed a significant decrease in frontal gray matter volume with increasing age in the autistic but not the control group. There was no association between age and white matter volume for either the autistic or control groups. Conclusions. The results of the current study suggest that macrocephalic and normocephalic subjects may be able to be combined in future studies. It is critical to examine frontal lobe morphology as a function of development, as study designs that control age may obscure important differences between autistic and control groups. Further research is needed to elucidate the mechanism(s) underlying the finding of decreased gray matter volume found with increasing age in autism. |
