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Thursday, May 7, 2009: 2:30 PM
Northwest Hall Room 2 (Chicago Hilton)
Background: Autism is a severe neurodevelopmental disorder that is characterized by impaired social interactions, impaired language development and repetitive, rigid behavior. Studies of brain changes in autism have often focused on the first two clusters of symptoms, despite the prominence of repetitive behavior in this disorder: in many cases these symptoms onset early in development and often form a significant impairment for affected individuals. Many studies have associated the basal ganglia with repetitive and stereotyped behavior across a range of neuropsychiatric disorders. In autism, conflicting reports of changes in the basal ganglia have been published. However, the developmental trajectory of the basal ganglia has not been examined in this disorder and conflicting results may in part reflect differences in developmental stage between samples. In this study, we investigate brain development cross-sectionally in high-functioning autism.
Objectives: To examine brain development in a homogeneous sample of subjects with high-functioning autism.
Methods: Structural MRI scans were acquired from 188 individuals aged between 6 and 25 years (99 subjects with high-functioning autism and 89 typically developing, matched controls). Twelve subjects with autism were using neuroleptic medication. An automatic image processing pipeline was used to determine the volume of total brain, gray and white matter of the cerebrum, cerebellum and lateral ventricle volumes. Basal ganglia structures were traced manually. Regional changes in the basal ganglia were investigated using voxel-based morphometry with correction for multiple comparisons using false discovery rate (alpha < 0.05, two-tailed). Multivariate analysis of variance was used to investigate differences in brain development between diagnostic groups, with diagnosis as a fixed factor and age as a co-variate. Linear and quadratic curves were fitted to investigate the shape of the developmental curves. To investigate the relationship of basal ganglia volume with behavior, correlations with measures of repetitive and stereotyped behavior were calculated.
Results: Developmental trajectories of the caudate nucleus, putamen and nucleus accumbens differed between subjects with autism and controls. Results were not accounted for by overall changes in brain volume or neuroleptic medication. The development of the caudate nucleus differed from typical most, as its volume increased with age in autism, while it decreased for controls. Voxel-based analysis showed that changes in striatum localized to the head of the caudate nucleus. Overall caudate nucleus volume was associated with repetitive behavior in autism.
Conclusions: We report changes in striatal development in autism, where caudate volume is associated with repetitive behaviors. This emphasizes the importance of striatum in the etiology of autism, in particular in the development of repetitive behavior that characterizes the disorder.
Objectives: To examine brain development in a homogeneous sample of subjects with high-functioning autism.
Methods: Structural MRI scans were acquired from 188 individuals aged between 6 and 25 years (99 subjects with high-functioning autism and 89 typically developing, matched controls). Twelve subjects with autism were using neuroleptic medication. An automatic image processing pipeline was used to determine the volume of total brain, gray and white matter of the cerebrum, cerebellum and lateral ventricle volumes. Basal ganglia structures were traced manually. Regional changes in the basal ganglia were investigated using voxel-based morphometry with correction for multiple comparisons using false discovery rate (alpha < 0.05, two-tailed). Multivariate analysis of variance was used to investigate differences in brain development between diagnostic groups, with diagnosis as a fixed factor and age as a co-variate. Linear and quadratic curves were fitted to investigate the shape of the developmental curves. To investigate the relationship of basal ganglia volume with behavior, correlations with measures of repetitive and stereotyped behavior were calculated.
Results: Developmental trajectories of the caudate nucleus, putamen and nucleus accumbens differed between subjects with autism and controls. Results were not accounted for by overall changes in brain volume or neuroleptic medication. The development of the caudate nucleus differed from typical most, as its volume increased with age in autism, while it decreased for controls. Voxel-based analysis showed that changes in striatum localized to the head of the caudate nucleus. Overall caudate nucleus volume was associated with repetitive behavior in autism.
Conclusions: We report changes in striatal development in autism, where caudate volume is associated with repetitive behaviors. This emphasizes the importance of striatum in the etiology of autism, in particular in the development of repetitive behavior that characterizes the disorder.