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: 9.47). 09/2009; 66(10):942-9. DOI: 10.1016/j.biopsych.2009.07.007
Source: PubMed

ABSTRACT 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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    • "Early brain overgrowth is commonly observed in individuals with autism spectrum disorders (ASDs) followed by abnormally slow brain growth, indicative of aberrant neurotrophin activity [1] [2] [3]. In particular, increased volume and abnormal functioning of the amygdala and hippocampus have been proposed to be the basis for impairments in social functioning and emotional perception that are characteristic of ASDs [4] [5] [6]. "
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    ABSTRACT: Evidence from clinical studies suggests that abnormal activity of brain derived neurotrophic factor (BDNF) contributes to the pathogenesis of autism spectrum disorders (ASDs). A genetically modified line of mice over-expressing a BDNF transgene in forebrain neurons was used to investigate if this mutation leads to changes in behavior consistent with ASD. The mice used in these experiments were behaviorally tested past 5 months of age when spontaneous seizures were evident. These seizures were not observed in age-matched wildtype (WT) mice or younger mice from this transgenic line. The BDNF mice in these experiments weighed less than their WT littermates. The BDNF transgenic (BDNF-tg) mice demonstrated similar levels of sociability in the social approach test. Conversely, the BDNF-tg mice demonstrated less obsessive compulsive-like behavior in the marble burying test, less anxiety-like behavior in the elevated plus maze test, and less depressive-like behavior in the forced swim test. Changes in behavior were found in these older mice that have not been observed in younger mice from this transgenic line, which may be due to the development of seizures as the mice age. These mice do not have an ASD phenotype but may be useful to study adult onset epilepsy.
    Behavioural brain research 04/2014; 268. DOI:10.1016/j.bbr.2014.04.025 · 3.39 Impact Factor
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    • "They, however do not provide analyses of gender effects within the autistic group. Nonetheless , following their results brain morphology of female patients relative to non-autistic women seems to be characterized by increases in brain volume particularly in the right temporoparietal junction and the bilateral superior frontal gyri [Calderoni et al., 2012] as well as in the amygdala [Schumann et al., 2009], altered gray and white matter density especially in limbic regions and frontotemporal cortices [Craig et al., 2007], or frontal and temporal cortical gray matter enlargement [Bloss & Courchesne, 2007; Schumann et al., 2010]. However, Sparks et al. [2002] and Nordahl et al. [2011] could not confirm overall brain enlargement in girls with autism but rather found increased brain size as an indicator for the level of regression in autistic boys [Nordahl et al., 2011]. "
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    ABSTRACT: Despite remarkable behavioral gender differences in patients with autism spectrum disorder (ASD), and growing evidence for a diminished male : female ratio for the putative "male disorder" ASD, aspects of gender are not addressed accordingly in ASD research. Our study aims at filling this gap by exploring empathy abilities in a group of 28 patients with high-functioning ASD and 28 gender-, age- and education-matched non-autistic subjects, for the first time by means of functional neuroimaging (fMRI). In an event-related fMRI paradigm, emotional ("E") and neutral ("N") video clips presented actors telling self-related short stories. After each clip, participants were asked to indicate their own emotion and its intensity as well as the emotion and intensity perceived for the actor. Behaviorally, we found significantly less empathic responses in the overall ASD group compared with non-autistic subjects, and inadequate emotion recognition for the neutral clips in the female ASD group compared with healthy women. Neurally, increased activation of the bilateral medial frontal gyrus was found in male patients compared with female patients, a pattern which was not present in the non-autistic group. Additionally, autistic women exhibited decreased activation of midbrain and limbic regions compared with non-autistic women, whereas there was no significant difference within the male group. While we did not find a fundamental empathic deficit in autistic patients, our data propose different ways of processing empathy in autistic men and women, suggesting stronger impairments in cognitive aspects of empathy/theory of mind for men, and alterations of social reciprocity for women. Autism Res 2013, ●●: ●●-●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
    Autism Research 12/2013; 6(6). DOI:10.1002/aur.1310 · 4.53 Impact Factor
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    • "Studies relating amygdala volume to the degree of social impairment have had mixed results. Two studies found social impairment correlated with decreases in amygdala volume (Nacewicz et al., 2006; Mosconi et al., 2009), one with larger amygdala volume (Schumann et al., 2009), and two others no relationship at all (Dziobek et al., 2006; Juranek et al., 2006). The two studies that found positive correlation assessed social ability by experimental procedures, such as eye-tracking, rating joint attention from camera recordings, or facial emotion recognition tasks (Nacewicz et al., 2006; Mosconi et al., 2009). "
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    ABSTRACT: Autism spectrum disorders (ASD) display significant heterogeneity. Although most neuroimaging studies in ASD have been designed to identify commonalities among affected individuals, rather than differences, some studies have explored variation within ASD. There have been two general types of approaches used for this in the neuroimaging literature to date: comparison of subgroups within ASD, and analyses using dimensional measures to link clinical variation to brain differences. This review focuses on structural and functional magnetic resonance imaging studies that have used these approaches to begin to explore heterogeneity between individuals with ASD. Although this type of data is yet sparse, recognition is growing of the limitations of behaviorally defined categorical diagnoses for understanding neurobiology. Study designs that are more informative regarding the sources of heterogeneity in ASD have the potential to improve our understanding of the neurobiological processes underlying ASD.
    Frontiers in Human Neuroscience 10/2013; 7:733. DOI:10.3389/fnhum.2013.00733 · 2.90 Impact Factor
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