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Comparative Study
. 2012 Jan;69(1):53-61.
doi: 10.1001/archgenpsychiatry.2011.145.

Increased rate of amygdala growth in children aged 2 to 4 years with autism spectrum disorders: a longitudinal study

Christine Wu Nordahl  1 , Robert Scholz, Xiaowei Yang, Michael H Buonocore, Tony Simon, Sally Rogers, David G Amaral
Affiliations
Comparative Study

Increased rate of amygdala growth in children aged 2 to 4 years with autism spectrum disorders: a longitudinal study

Christine Wu Nordahl et al. Arch Gen Psychiatry. 2012 Jan.

Abstract

Context: Precocious amygdala enlargement is commonly observed in young children with autism. However, the age at which abnormal amygdala enlargement begins and the relative growth trajectories of the amygdala and total brain remain unclear.

Objective: To determine whether the rate of amygdala growth is abnormal and disproportionate to total brain growth in very young children with autism spectrum disorders (ASDs).

Design: Longitudinal structural magnetic resonance imaging study.

Setting: Neuroimaging and diagnostic assessments were performed at an academic medical center. Participants were recruited from the community.

Participants: Baseline scans were acquired in 132 boys (85 with ASD and 47 control subjects with typical development [TD]; mean age, 37 months). Longitudinal magnetic resonance images were acquired in 70 participants (45 with ASD and 25 TD controls) 1 year later.

Main outcome measure: Amygdala volumes and total cerebral volumes (TCVs) were evaluated at both time points, and 1-year growth rates were calculated.

Results: The amygdala was larger in children with ASD at both time points, but the magnitude of enlargement was greater at time 2. The TCV was also enlarged in the children with ASD by the same magnitude at both time points. When we controlled for TCV, amygdala enlargement remained significant at both time points. The rate of amygdala growth during this 1-year interval was faster in children with ASD than in TD controls. The rate of TCV growth did not differ between groups. Post hoc exploratory analyses revealed 3 patterns of amygdala and TCV growth rates in the ASD group.

Conclusions: Disproportionate amygdala enlargement is present by 37 months of age in ASD. The amygdala continues to grow at an increased rate, but substantial heterogeneity exists in amygdala and TCV growth patterns. Future studies aimed at clinical characterization of different growth patterns could have implications for choice and outcomes of treatment and behavioral therapy.

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Figures

Figure 1
Figure 1
An example of distortion correction in a standard-calibration phantom and a corresponding brain image. The phantom is made of clear urethane material containing polycarbonate spheres filled with a copper sulfate solution. Measurements of the phantom are compared with the known positions of the spheres to give an accurate measurement of the distortion of the scanner. A, Uncorrected phantom (top) and subject (bottom) images. Distortion (the maximal amount observed in this study) is readily seen as bending lines in the phantom image, particularly in zones where the distortion is greater than 10 mm (arrows; outside the red isocontour). B, Distortion-corrected images of phantom (top) and brain (bottom) images. Three-dimensional distortion maps are derived from the raw phantom image and used to produce corrected phantom and participant images.
Figure 2
Figure 2
Group comparison of amygdala volumes at both magnetic resonance imaging time points. The box plots depict the median and 25th and 75th percentiles. The whiskers denote the 10th and 90th percentiles. Values above the 90th and below the 10th percentiles are plotted as points The amygdala is enlarged in the autism spectrum disorder (ASD) group at both time points, but the magnitude of the difference is greater at time 2. TD indicates controls with typical development. *P< .05. † P< .01. P values are adjusted for age and total cerebral volume.
Figure 3
Figure 3
Trajectories of amygdala growth for the autism spectrum disorder (ASD) group and control subjects with typical development (TD). A and B, Individual trajectories of amygdala growth during a 1-year interval from 37 to 50 months of age. C and D, Mean trajectories of growth for the ASD and TD groups averaged for each magnetic resonance imaging time point.
Figure 4
Figure 4
Percentage increase in brain regions during the 1-year interval A, Left and right amygdalas. B, Total cerebral volume (TCV). ASD indicates autism spectrum disorder; TD, control subjects with typical development. *P< .05. † P< .01. P values are adjusted for the percentage increase in TCV and the interval between scans.
Figure 5
Figure 5
Patterns of development of the amygdala and total cerebral volume (TCV) in subgroups of patients with autism spectrum disorder (ASD). A, Rate of amygdala growth relative to TCV growth plotted against age at the time 1 magnetic resonance imaging. Individuals in whom the amygdala was growing more rapidly than the TCV are plotted above 0 (gray line), whereas those whose rate of TCV expansion exceeded the rate of amygdala expansion are plotted below 0. Three ASD subgroups are defined according to the 95% CIs for the control subjects with typical development (TD) (dashed lines). Relative to the TD group, the ASD–amygdala rapid group exhibited double the rate of amygdala growth. Conversely, ASD–amygdala slow group exhibited normal amygdala growth rates but increased rate for TCV growth. A final subgroup, the ASD-typical group, exhibited amygdala and TCV growth rates that were very similar to those of the TD group. B, Percentage increases during the 1-year interval for amygdala and TCV for the 3 ASD subgroups and TD group.
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