A preliminary longitudinal volumetric MRI study of amygdala and hippocampal volumes in autism

https://doi.org/10.1016/j.pnpbp.2013.09.010Get rights and content

Highlights

  • This is a pilot investigation of hippocampal and amygdala development in autism.

  • Participants with autism and controls were 8–14 years of age.

  • Amygdala volume changes with time were similar between the two groups.

  • Amygdala volume change correlated with the ability to establish eye contact.

  • Hippocampal volume change with time between the groups approached significance.

Abstract

Background

Previous studies suggest that amygdala volume, when compared with healthy controls, is increased in young children with autism, is unchanged in cohorts of older youth, and is smaller in adults. Hippocampal volume, however, does not appear to have age-related changes, and it is unclear whether individuals with autism have volumetric differences in this structure. The goal of this pilot investigation is to characterize the developmental trajectories of the amygdala and hippocampus in children with autism between the ages of 8 and 14 years and to examine clinical correlates of volume change.

Methods

Twenty-three children with autism and 23 controls between the ages of 8 and 12 underwent a magnetic resonance imaging procedure of the brain (T1-weighted) at two time points. Nine children with autism and 14 controls had good quality scans from both time points; however, all usable scans from all subjects (15 children with autism and 22 controls) were included in a mixed effect analysis. Regression models were used to estimate group differences in amygdala and hippocampal volumes. Changes in amygdala and hippocampal volumes (Time 2  Time 1) were correlated with clinical severity measures.

Results

Amygdala volume changes with time were similar between the two groups. Within the autism group, right amygdala volume change was correlated with the ability to establish appropriate eye contact. Right hippocampal volume was significantly increased in the autism group when compared with controls. Differences in right hippocampal volume change with time between the two groups approached significance.

Conclusion

This study provides preliminary evidence of normalization of amygdala volumes in late childhood and adolescence. It also suggests that hippocampal volumetric differences may exist in autism in late childhood and adolescence.

Introduction

The amygdala and hippocampus have been implicated in deficits associated with Autism Spectrum Disorders (ASD), including social cognition, perception of eye-gaze direction, and emotion (Conty and Grezes, 2011, Fanselow and Dong, 2010, Greicius et al., 2003, Kawashima et al., 1999). To date, all MRI investigations examining amygdala and hippocampal volumes were cross-sectional with the exception of two recent studies that reported on the size of the amygdala in young children with autism (Mosconi et al., 2009, Nordahl et al., 2012). Cross-sectional studies confound within- and between-subject source of variations and cannot capture changes in the trajectories (Stanfield et al., 2008, Thompson et al., 2011). However, there is mounting evidence from these cross-sectional studies, suggesting that, compared with controls, amygdala volume is increased in young children with autism (Kim et al., 2010a, Kim et al., 2010b, Mosconi et al., 2009, Munson et al., 2006, Nordahl et al., 2012, Schumann et al., 2009, Sparks et al., 2002), is unchanged in cohorts of older youth (Bigler et al., 2003, Haznedar et al., 2000, Palmen et al., 2006) and is smaller in adults (Aylward et al., 1999, Nacewicz et al., 2006, Pierce and Courchesne, 2001, Rojas et al., 2004). In contrast, findings from cross-sectional studies of hippocampal volume in autism have not been consistent and no clear age-related changes have emerged. This observation could be related to the heterogeneity of the samples included in those investigations or to the actual absence of a developmental effect.

The goal of this investigation is to characterize the developmental trajectories of the amygdala and hippocampus in a small group of children with autism between the ages of 8 and 14 years and to examine any possible clinical correlates of volume change.

Section snippets

Participants (Table 1)

The original sample included 46 male participants. Good quality scans were available on 37 subjects, 15 with autism and 22 healthy controls (age range at baseline: autism: 8.1–12.9 years; controls: 7.9–13; age range at follow-up: autism 10.9–14.3 years, controls: 10.1–14.1, p(Time 1) = 0.675, p(Time 2) = 0.561).

Autism participants met the following inclusion criteria: 1) diagnosis of autistic disorder through expert clinical evaluation confirmed with the Autism Diagnostic Interview—Revised (ADI-R) (

Results

Of the 15 participants with autism with good quality scans, 14 had data at Time 1 and 10 had data at Time 2. Of the 22 controls with good quality scans, 19 had data at Time 1 and 17 at Time 2. Complete data at both time points was available for 9 youth with autism and 14 controls.

There were no significant differences between the baseline SES of the two groups (t = 0.06, p = 0.949). There was a significant difference between baseline FSIQ scores (mean FSIQ for autism = 98.1 ± 20.1; mean FSIQ for controls

Discussion

In this study we examined the developmental trajectory of amygdala and hippocampal volumes in children and adolescents with autism compared to age- and gender-matched typically developing controls. Specifically, in our sample, amygdala volumes as well as volume increases with age were similar in individuals with autism and controls. In addition, within the autism group, volume change of the right amygdala was correlated with the capability to establish appropriate eye contact, which is an

Conclusion

This study provides preliminary evidence of the possible normalization of amygdala volumes in late childhood and adolescence. It also suggests that hippocampal volumetric differences may exist in autism in late childhood and adolescence. Additional investigations are warranted to examine longitudinal samples across a wide age range, at multiple time points, to estimate developmental trajectories of the amygdala and hippocampus and their relationships to clinical features.

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