No differences in MR-based volumetry between 2- and 7-year-old children with autism spectrum disorder and developmental delay

Abstract

Objective

To study brain volumes in children with ASD as compared to children with a mental retardation or a language delay (developmentally delayed). In addition, to study the association of intellectual functioning on brain volumes in children with ASD or developmental delay. Methods: Thirty-four children with ASD and 13 developmentally delayed children without ASD, between 2 and 7 years old, matched on age and developmental level, participated in a MRI study. Volumes of cranium, total brain, cerebellum, grey and white matter, ventricles, hippocampus and amygdala were measured. Results: No significant differences in volumes of intracranium, total brain, ventricles, cerebellum, grey or white matter or amygdala and hippocampus between the ASD group and the developmentally delayed group were found. In the developmentally delayed group, a significant correlation (0.73) was found between intellectual functioning and total brain volume after partialling out intracranial volume. In the ASD group, the correlation between intellectual functioning and brain volume corrected for intracranial volume was not significant. Conclusion: No evidence was found for overall differences in brain volumes in children with ASD compared to developmentally delayed children between 2 and 7 years. The finding that higher intellectual functioning was not associated with a relative larger brain volume in children with ASD may suggest that a relative enlargement of the brain may not be beneficial to patients with autism.

Introduction

Autism is a pervasive developmental disorder characterized by a triad of social deficits, language and communication problems and a pattern of stereotyped, repetitive and restricted behaviours and interests [1]. It is a clinically heterogeneous condition that has a broad range of severity and is frequently associated with concomitant learning disabilities. A wide variety of brain abnormalities has been reported by neuroanatomic and neuroimaging studies [2], [3], [4], [5]. Although the clinical manifestations of the disorder by definition are present before age three, brain development may be impacted much earlier, possibly as early as the first year of life [6]. Three studies have been published that were specifically aimed at children under the age of five [7], [8], [9] – see also Table 1. The first study published [9] reports that by ages 2–4 years 90% of autistic boys had a brain volume larger than normal average and 37% met criteria for developmental macrencephaly (brain volume that exceeds 2 SD above the normal mean). Autistic 2- and 3-year-old had more cerebral (18% volume increase) and cerebellar white matter (39% volume increase), and more cerebral cortical grey matter (12% volume increase) than normal. Sparks and colleagues [8] also found significantly increased cerebral and cerebellar volumes in children with ASD compared with typically developing and developmentally delayed children. In the most recent volumetric study, significant enlargement was detected in cerebral cortical volumes, but not in cerebellar volumes in individuals with autism [7]. Enlargement was present in both grey and white matter, and it was found throughout the cerebral cortex. In the first two studies of children with autism between 2 and 5 years, brain volume was found to be approximately 10% larger than in typically developing children [8], [9]. In the third study, in which the children were younger, this was approximately 5% [7].

We report here the results of our study of brain volumes of 47 children with an autism spectrum disorder, mental retardation, or a language delay between the ages of 21 and 77 months. We also examined the correlation between intellectual functioning and brain volumes.