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 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:
    Social Cognitive and Affective Neuroscience 05/2015; DOI:10.1093/scan/nsv053 · 7.37 Impact Factor
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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.
    Clinical neuroimaging 04/2015; 8. DOI:10.1016/j.nicl.2015.04.008 · 2.53 Impact Factor
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    • "In the current study, we analyzed anatomical data acquired from individuals older than 6 years of age for whom MRI scans are available in the Autism Brain Imaging Data Exchange (ABIDE) database. Previous studies of individuals in this age range have reported that, in comparison to controls, ASD individuals exhibit numerous abnormalities including larger gray matter (Lotspeich et al. 2004; Hazlett et al. 2006; Ecker et al. 2013), white matter (Hazlett et al. 2006), amygdala (Bellani et al. 2013a), and hippocampus (Groen et al. 2010) volumes, smaller cerebellum (Scott et al. 2009; Fatemi et al. 2012) and corpus callosum (CC; Bellani et al. 2013b) volumes, and abnormal cortical thickness (Raznahan et al. 2010; Wallace et al. 2010). These findings have been interpreted as supporting evidence for different theories of ASD including, for example, the " amygdala theory of autism " (Baron-Cohen et al. 2000) and the " underconnectivity " theory of ASD (Just et al. 2007). "
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    ABSTRACT: Substantial controversy exists regarding the presence and significance of anatomical abnormalities in autism spectrum disorders (ASD). The release of the Autism Brain Imaging Data Exchange (∼1000 participants, age 6-65 years) offers an unprecedented opportunity to conduct large-scale comparisons of anatomical MRI scans across groups and to resolve many of the outstanding questions. Comprehensive univariate analyses using volumetric, thickness, and surface area measures of over 180 anatomically defined brain areas, revealed significantly larger ventricular volumes, smaller corpus callosum volume (central segment only), and several cortical areas with increased thickness in the ASD group. Previously reported anatomical abnormalities in ASD including larger intracranial volumes, smaller cerebellar volumes, and larger amygdala volumes were not substantiated by the current study. In addition, multivariate classification analyses yielded modest decoding accuracies of individuals' group identity (<60%), suggesting that the examined anatomical measures are of limited diagnostic utility for ASD. While anatomical abnormalities may be present in distinct subgroups of ASD individuals, the current findings show that many previously reported anatomical measures are likely to be of low clinical and scientific significance for understanding ASD neuropathology as a whole in individuals 6-35 years old.
    Cerebral Cortex 10/2014; DOI:10.1093/cercor/bhu242 · 8.67 Impact Factor
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