Amygdala and Hippocampus Enlargement During Adolescence in Autism

Donders Institute for Brain Cognition and Behavior, Centre for Cognitive Neuroimaging, Nijmegen, The Netherlands.
Journal of the American Academy of Child and Adolescent Psychiatry (Impact Factor: 7.26). 06/2010; 49(6):552-60. DOI: 10.1016/j.jaac.2009.12.023
Source: PubMed


The amygdala and hippocampus are key components of the neural system mediating emotion perception and regulation and are thought to be involved in the pathophysiology of autism. Although some studies in children with autism suggest that there is an enlargement of amygdala and hippocampal volume, findings in adolescence are sparse.
We measured amygdala and hippocampus volume in a homogeneous group of adolescents with autism (12 through 18 years; n = 23) and compared them with an age-, sex-, and IQ-matched control group (n = 29) using a validated automated segmentation procedure in 1.5-T magnetic resonance images. All analyses were adjusted for total brain volume.
Repeated-measures analysis revealed a significant group x hemisphere x brain structure interaction (p = .038), even when corrected for total brain volume. Post-hoc analysis showed that the right amygdala and left hippocampus were significantly enlarged (p = .010; p = .015) in the autism compared with the control group. There were no significant correlations between age and amygdala or hippocampus volume.
The abnormal enlargement of the amygdala and hippocampus in adolescents with autism adds to previous findings of enlargement of these structures in children with autism. This may reflect increased activity of these structures and thereby altered emotion perception and regulation. Our results could therefore be interpreted in light of developmental adaptation of the autistic brain to a continuous overflow of emotional learning experiences.

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    • "The ASD group also exhibited reduced right entire amygdala connectivity with the right superior parietal lobe. Partial correlation analysis revealed that this difference was mainly driven by the right LB. Prior research showed that functional specialization of amygdaloid subregions continues throughout adolescence[70,72]and that volumetric abnormalities in ASD are age specific[10,11]. The possibility that our between-group effects were driven by developmental differences was however not supported by our data. "
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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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    • "The amygdala projects to several brain structures in the frontal cortex , hippocampus, striatum, hypothalamus and brain stem (LeDoux, 2000; Gordon and Hen, 2004; Tottenham and Sheridanm, 2009; Tottenham, 2012) and is considered to have critical involvement in the behavioral activation and inhibition system that characterizes emotional responses such as fear and anxiety (Gray, 1994; Gray and McNaughton, 2000). Volumetric imaging work in pediatric patient populations, such as youth with autism, bipolar disorder and post-traumatic stress disorder (PTSD) symptoms has tended to focus on amygdala volume comparisons with age and gender-matched comparison youth (De Bellis et al., 1999; Carrió n et al., 2001, 2010; Chen et al., 2004; Groen et al., 2010). However, studies examining volumetric differences of the amygdala have often failed to show significant differences (Weems et al., 2013). "
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    ABSTRACT: Theoretically, normal developmental variation in amygdala volumes may be altered under conditions of severe stress. The purpose of this paper was to examine if posttraumatic stress moderates the association between age and amygdala volumes in youth exposed to traumatic events who are experiencing symptoms of posttraumatic stress disorder. Volumetric imaging was conducted on two groups of youth aged 9-17 years: twenty-eight with exposure to trauma and post-traumatic stress disorder symptoms (PTSD; boys = 15, girls = 13) and twenty-six matched (age, IQ) comparison youth (Controls; boys = 12, girls = 14). There was a significant group by age interaction in predicting right amygdala volumes. A positive association between age and right amygdala volumes was observed, but only in PTSD youth. These associations with age remained when controlling for IQ, total brain volumes, and sex. Moreover, older youth with PTSD symptoms had relatively larger right amygdala volumes than controls. Findings provide evidence that severe stress may influence age related variation in amygdala volumes. Results further highlight the importance of utilizing age as an interactive variable in pediatric neuroimaging research, in so far as age may act as an important moderator of group differences. © The Author (2015). Published by Oxford University Press. For Permissions, please email:
    Full-text · Article · May 2015 · Social Cognitive and Affective Neuroscience
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    • "Inconsistency is apparent in the literature on hippocampal volume in children with ASD and youth. While some studies have reported an increase in volume (Schumann et al., 2004; Groen et al., 2010), others have found no change (Palmen et al., 2006)orevenadecrease in volume (Aylward et al., 1999). Alterations have also been found in the caudate, which has been reported to be increased in volume in adolescents and adults with ASD (Rojas et al., 2006; Brambilla et al., 2003; Nickl-Jockschat et al., 2012; Sears et al., 1999). "
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    ABSTRACT: Autism Spectrum Disorder (ASD) is a clinically diagnosed, heterogeneous, neurodevelopmental condition, whose underlying causes have yet to be fully determined. A variety of studies have investigated either cortical, subcortical, or cerebellar anatomy in ASD, but none have conducted a complete examination of all neuroanatomical parameters on a single, large cohort. The current study provides a comprehensive examination of brain development of children with ASD between the ages of 4 and 18 years who are carefully matched for age and sex with typically developing controls at a ratio of one-to-two. Two hundred and ten magnetic resonance images were examined from 138 Control (116 males and 22 females) and 72 participants with ASD (61 males and 11 females). Cortical segmentation into 78 brain-regions and 81,924 vertices was conducted with CIVET which facilitated a region-of-interest- (ROI-) and vertex-based analysis, respectively. Volumes for the cerebellum, hippocampus, striatum, pallidum, and thalamus and many associated sub regions were derived using the MAGeT Brain algorithm. The study reveals cortical, sub-cortical and cerebellar differences between ASD and Control group participants. Diagnosis, diagnosis-by-age, and diagnosis-by-sex interaction effects were found to significantly impact total brain volume but not total surface area or mean cortical thickness of the ASD participants. Localized (vertex-based) analysis of cortical thickness revealed no significant group differences, even when age, age-range, and sex were used as covariates. Nonetheless, the region-based cortical thickness analysis did reveal regional changes in the left orbitofrontal cortex and left posterior cingulate gyrus, both of which showed reduced age-related cortical thinning in ASD. Our finding of region-based differences without significant vertex-based results likely indicates non-focal effects spanning the entirety of these regions. The hippocampi, thalamus, and globus pallidus, were smaller in volume relative to total cerebrum in the ASD participants. Various sub-structures showed an interaction of diagnosis-by-age, diagnosis-by-sex, and diagnosis-by-age-range, in the case where age was divided into childhood (age < 12) and adolescence (12 < age < 18). This is the most comprehensive imaging-based neuro-anatomical paediatric and adolescent ASD study to date. These data highlight the neurodevelopmental differences between typically developing children and those with ASD, and support aspects of the hypothesis of abnormal neuro-developmental trajectory of the brain in ASD.
    Full-text · Article · Apr 2015 · Clinical neuroimaging
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