Regional alterations in purkinje cell density in patients with autism

Neuropathological studies, using a variety of techniques, have reported a decrease in Purkinje cell (PC) density in the cerebellum in autism. We have used a systematic sampling technique that significantly reduces experimenter bias and variance to estimate PC densities in the postmortem brains of eight clinically well-documented individuals with autism, and eight age- and gender-matched controls. Four cerebellar regions were analyzed: a sensorimotor area comprised of hemispheric lobules IV-VI, crus I & II of the posterior lobe, and lobule X of the flocculonodular lobe. Overall PC density was thus estimated using data from all three cerebellar lobes and was found to be lower in the cases with autism as compared to controls, an effect that was most prominent in crus I and II (p<0.05). Lobule X demonstrated a trend towards lower PC density in only the males with autism (p = 0.05). Brain weight, a correlate of tissue volume, was found to significantly contribute to the lower lobule X PC density observed in males with autism, but not to the finding of lower PC density in crus I & II. Therefore, lower crus I & II PC density in autism is more likely due to a lower number of PCs. The PC density in lobule X was found to correlate with the ADI-R measure of the patient's use of social eye contact (R² = -0.75, p = 0.012). These findings support the hypothesis that abnormal PC density may contribute to selected clinical features of the autism phenotype.