Amygdala Enlargement in Toddlers with Autism Related to Severity of Social and Communication Impairments

Department of Neurosciences, Autism Center of Excellence, University of California, San Diego, La Jolla, CA 92037, USA.
Biological psychiatry (Impact Factor: 10.26). 09/2009; 66(10):942-9. DOI: 10.1016/j.biopsych.2009.07.007
Source: PubMed


Autism is a heterogeneous neurodevelopmental disorder of unknown etiology. The amygdala has long been a site of intense interest in the search for neuropathology in autism, given its role in emotional and social behavior. An interesting hypothesis has emerged that the amygdala undergoes an abnormal developmental trajectory with a period of early overgrowth in autism; however this finding has not been well established at young ages nor analyzed with boys and girls independently.
We measured amygdala volumes on magnetic resonance imaging scans from 89 toddlers at 1-5 years of age (mean = 3 years). Each child returned at approximately 5 years of age for final clinical evaluation.
Toddlers who later received a confirmed autism diagnosis (32 boys, 9 girls) had a larger right (p < .01) and left (p < .05) amygdala compared with typically developing toddlers (28 boys, 11 girls) with and without covarying for total cerebral volume. Amygdala size in toddlers with autism spectrum disorder correlated with the severity of their social and communication impairments as measured on the Autism Diagnostic Interview and Vineland scale. Strikingly, girls differed more robustly from typical in amygdala volume, whereas boys accounted for the significant relationship of amygdala size with severity of clinical impairment.
This study provides evidence that the amygdala is enlarged in young children with autism; the overgrowth must begin before 3 years of age and is associated with the severity of clinical impairments. However, neuroanatomic phenotypic profiles differ between males and females, which critically affects future studies on the genetics and etiology of autism.

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    • "The amygdala theory of autism describes this structure as potential key component in the pathogenesis of ASD[7,8], since it is involved inwfi various aspects of the social brain, such as so- cial cognition, emotion recognition, sociocommunicative perception, and the regulation of emotional responses[9]. In line with this, individuals with ASD tend to show abnormal volume enlargements of the amygdala[10,11]and have overactive amygdalae in response to mildly aversive stimuli[12]and faces[13], while symptom severity in ASD has been found to correlate with amygdala size[10,14,15]. Although amygdala impairments likely relate to pathophysiological socio-emotional processes, its subregionspecific amygdalo-cortical abnormalities have not been stratified in ASD. "
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    ABSTRACT: Amygdala dysfunction is hypothesized to underlie the social deficits observed in autism spectrum disorders (ASD). However, the neurobiological basis of this hypothesis is underspecified because it is unknown whether ASD relates to abnormalities of the amygdaloid input or output nuclei. Here, we investigated the functional connectivity of the amygdaloid social-perceptual input nuclei and emotion-regulation output nuclei in ASD versus controls. We collected resting state functional magnetic resonance imaging (fMRI) data, tailored to provide optimal sensitivity in the amygdala as well as the neocortex, in 20 adolescents and young adults with ASD and 25 matched controls. We performed a regular correlation analysis between the entire amygdala (EA) and the whole brain and used a partial correlation analysis to investigate whole-brain functional connectivity uniquely related to each of the amygdaloid subregions. Between-group comparison of regular EA correlations showed significantly reduced connectivity in visuospatial and superior parietal areas in ASD compared to controls. Partial correlation analysis revealed that this effect was driven by the left superficial and right laterobasal input subregions, but not the centromedial output nuclei. These results indicate reduced connectivity of specifically the amygdaloid sensory input channels in ASD, suggesting that abnormal amygdalo-cortical connectivity can be traced down to the socio-perceptual pathways.
    Full-text · Article · Dec 2016 · Molecular Autism
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    • "No previous work has examined predictive relations between autonomic arousal and later social abilities in unaffected siblings of children with ASD; however, several studies have found concurrent relations between these measures in older children and adolescents with ASD, and together, this work suggests that successful modulation of sympathetic responses relates to better social functioning (e.g., Bal et al., 2010; Joseph et al., 2008; Van Hecke et al., 2009). Studies of the structure and 16 function of the amygdala have also found associations between activation of the amygdala to faces and visual social attention (Dalton et al., 2005) as well as between the size of the amygdala and ASD symptomology (Schumann, Barnes, Lord, & Courchesne, 2009). Overall, this body of work with individuals with ASD raises questions of whether the regulation of these neural and physiological responses might not only have an impact on emotional reactivity during social situations, but whether individual differences in these responses might be associated with variability in social-communicative functioning (Van Hecke et al., 2009). "
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    ABSTRACT: When scanning faces, individuals with autism spectrum disorder (ASD) have shown reduced visual attention (e.g., less time on eyes) and atypical autonomic responses (e.g., heightened arousal). To understand how these differences might explain subclinical variability in social functioning, 9-month-olds, with or without a family history of ASD, viewed emotionally expressive faces, and gaze and pupil diameter (a measure of autonomic activation) were recorded using eye-tracking. Infants at high risk for ASD with no subsequent clinical diagnosis (HRA-) and low-risk controls (LRC) showed similar face scanning and attention to eyes and mouth; attention was overall greater to eyes than mouth, but this varied as a function of the emotion presented. As a group, HRA- showed significantly larger pupil size than LRC. Correlations between scanning at 9 months, pupil size at 9 months, and 18-month social-communicative behavior, revealed positive associations between pupil size and attention to both face and eyes at 9 months in LRC, and a negative association between 9-month pupil size and 18-month social-communicative behavior in HRA-.The present findings point to heightened autonomic arousal in HRA-. Further, with greater arousal relating to worse social-communicative functioning at 18 months, this work points to a mechanism by which unaffected siblings might develop atypical social behavior.
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    • "In contrast, amygdala volumes only differed concerning the life-span trajectories: Unlike the control persons, who displayed increasing amygdala volumes over time, persons with ASD (on a trend level) showed a decrease of bilateral amygdala volumes. The result of differing time-trajectories of amygdala volumes fits to the pattern of former findings, reporting enlarged amygdala volumes in smaller children with ASD (Sparks et al., 2002; Mosconi et al., 2009; Schumann et al., 2009), reduced amygdala volumes in adolescents and adults with ASD (Aylward et al., 1999; Nacewicz et al., 2006), and an age-dependent increase of amygdala volumes in controls but not in persons with ASD (Murphy et al., 2012). "
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    ABSTRACT: Previous studies concerning the volumes of the amygdala and the hippocampus in autism spectrum disorders (ASD) show inconsistent results. We acquired magnetic resonance images of 30 individuals with ASD and individually matched controls. All participants had an IQ>100 to increase the likelihood of including non-syndromal forms of ASD. Manually defined amygdala volumes showed no significant group difference, while hippocampi were significantly enlarged in ASD. This finding is discussed with regard to the 'intense world hypothesis'. Copyright © 2015. Published by Elsevier Ireland Ltd.
    No preview · Article · Aug 2015 · Psychiatry Research: Neuroimaging
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