Elsevier

Biological Psychiatry

Volume 66, Issue 4, 15 August 2009, Pages 327-333
Biological Psychiatry

Archival Report
Changes in the Developmental Trajectories of Striatum in Autism

https://doi.org/10.1016/j.biopsych.2009.03.017Get rights and content

Background

Repetitive and stereotyped behavior has been associated with striatum in various neuropsychiatric disorders. However, striatal involvement has not yet been shown conclusively in autism. Issues include the use of neuroleptic medication and differences in mean age between samples, where conflicting results may reflect differences in developmental stage between samples. The objective was to examine brain development in a homogeneous sample of subjects with high-functioning autism.

Methods

Magnetic resonance measures of brain structure of 188 individuals (99 subjects with high-functioning autism and 89 typically developing, matched control subjects) aged between 6 years and 25 years were compared. Measurements included the volume of brain structures, including striatum, as well as voxel-based assessment of gray matter density.

Results

Developmental trajectories of the caudate nucleus, putamen, and nucleus accumbens differed between subjects with autism and control subjects. 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 control subjects. 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, while 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.

Section snippets

Participants

Ninety-nine, high-functioning individuals meeting DSM-IV criteria for autism were recruited through the Department of Child and Adolescent Psychiatry at the University Medical Center in Utrecht, the National Autism Society in the Netherlands, an outpatient clinic for individuals with pervasive developmental disorders, and through advertising. Diagnosis was clinically established by a child and adolescent psychiatrist from our department and was confirmed by trained and qualified clinicians

Group Differences in Brain Development

The primary multivariate analysis showed interactions between diagnosis and age for caudate nucleus volume (F = 12.8, p < .001) and lateral ventricle volume (F = 4.2, p = .042); there was a main effect of diagnosis on caudate nucleus volume (F = 7.5, p = .007) and a main effect of age on cerebellum, gray matter, white matter, nucleus accumbens, lateral ventricle, and total brain volume.

After including total brain volume as a covariate in the model, the interaction between age and diagnosis

Discussion

In this study, we report changes in the trajectory of striatal development in autism. Differences in caudate development were particularly striking, as the volume of this structure increased with development in autism, while it decreased in control subjects. Changes were not attributable to changes in overall brain volume or the use of neuroleptic medication and were localized to the head of the caudate nucleus. Furthermore, caudate volume was associated with severity of repetitive behavior

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