Progress in Neuro-Psychopharmacology and Biological Psychiatry
A preliminary longitudinal volumetric MRI study of amygdala and hippocampal volumes in autism
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.
References (39)
- et al.
The amygdala: is it an essential component of the neural network for social cognition?
Neuropsychologia
(2003) - et al.
White matter integrity and executive abilities in individuals with phenylketonuria
Mol Genet Metab
(2013) - et al.
The amygdala theory of autism
Neurosci Biobehav Rev
(2000) - et al.
Processing of facial expressions and their significance for the observer in subregions of the human amygdala
Neuroimage
(2011) - et al.
Are the dorsal and ventral hippocampus functionally distinct structures?
Neuron
(2010) - et al.
Amygdalar, hippocampal, and thalamic volumes in youth at high risk for development of bipolar disorder
Psychiatry Res
(2011) - et al.
The expression of non-clustered protocadherins in adult rat hippocampal formation and the connecting brain regions
Neuroscience
(2010) - et al.
Evidence for a cerebellar role in reduced exploration and stereotyped behavior in autism
Biol Psychiatry
(2001) - et al.
Amygdala enlargement in toddlers with autism related to severity of social and communication impairments
Biol Psychiatry
(2009) - et al.
Contributions of total body fat, abdominal subcutaneous adipose tissue compartments, and visceral adipose tissue to the metabolic complications of obesity
Metabolism
(2001)
Towards a neuroanatomy of autism: a systematic review and meta-analysis of structural magnetic resonance imaging studies
Eur Psychiatry
Neural correlates to seen gaze-direction and head orientation in the macaque monkey amygdala
Neuroscience
Amygdala responses to averted vs direct gaze fear vary as a function of presentation speed
Soc Cogn Affect Neurosci
MRI volumes of amygdala and hippocampus in non-mentally retarded autistic adolescents and adults
Neurology
Controlling the false discovery rate: a practical and powerful approach to multiple testing
J R Stat Soc
On the adaptive control of the false discovery rate in multiple testing with independent statistics
J Educ Behav Stat
Temporal lobe, autism, and macrocephaly
AJNR Am J Neuroradiol
Puberty influences medial temporal lobe and cortical gray matter maturation differently in boys than girls matched for sexual maturity
Cereb Cortex
Look at me, I'll remember you: the perception of self-relevant social cues enhances memory and right hippocampal activity
Hum Brain Mapp
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