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There is substantial imaging evidence for volumetric abnormalities of the amygdala in younger children with autism spectrum disorder (ASD). The amygdala can be divided into functionally distinct laterobasal, superficial, and centromedial subregions. To date, we are not aware of any in vivo reports specifically assessing subregional amygdalar abnormalities in individuals with ASD.To evaluate alterations in subregional amygdalar morphology in children with ASD compared with typically developing (TD) children and to examine the relationships with ASD symptom severity.A cross-sectional study encompassing a narrow age range of children with ASD and age-matched TD children that evaluated magnetic resonance imaging-defined subregional morphology of the amygdala using a novel subregional analytic method.Participants were recruited and clinically evaluated through the University of Washington Autism Center and imaged at the Diagnostic Imaging Sciences Center at the University of Washington. Imaging data were analyzed through the Brain Imaging Laboratory at the Seoul National University.Fifty-one children 6 to 7 years of age (ASD, n = 31 and TD, n = 20) were assessed using magnetic resonance imaging and behavioral measures.Volume and subregional measures of the amygdala and measures of social and communication functioning.The ASD group exhibited larger right and left amygdalae, by 12.7% and 11.0%, respectively, relative to the TD group. Subregional analysis revealed that the ASD group had enlarged laterobasal amygdalar subregions, relative to the TD group, after adjusting for age, sex, and hemispheric cerebral volume (P.05, false discovery rate corrected and with clustered surface points15). Exploratory analyses revealed that there were linear trends comparing a strictly defined subgroup of children with autistic disorder, who exhibited the greatest extent of laterobasal enlargement, followed by a subgroup of children with pervasive developmental disorder not otherwise specified and then the group of TD children (P for linear trend.001). There were linear trends between enlargement of laterobasal subregions and lower levels of social and communication functioning (P.001, P.001, and P = .001 for 3 areas in the right laterobasal subregion; P.001 for 1 area in the left laterobasal subregion).The current study demonstrates bilateral enlargement of laterobasal subregions of the amygdala in 6- to 7-year-old children with ASD and that subregional alterations are associated with deficits in social and communicative behavior.

Context The brain pathophysiological abnormalities underlying autism remain unclear. Neuroimaging and histological studies suggest cellular abnormalities early in the course of the disease. Objective To measure the in vivo chemical profile of gray and white matter tissues in autism. Design Cross-sectional spectroscopic imaging study comparing 3- to 4-year-old children with autism spectrum disorder (ASD) with age-matched comparison groups of children with delayed development (DD) and typical development (TD). Setting The University of Washington Diagnostic Imaging Sciences Center, Seattle. Participants Forty-five 3- to 4-year-old children with ASD, 12 age-matched children with DD, and 10 age-matched children with TD. Main Outcome Measures Estimates of gray and white matter concentrations for choline-containing compounds (Cho), creatine plus phosphocreatine, N -acetylaspartate (NAA), and myo -inositol (mI). Transverse relaxation times for Cho, creatine plus phosphocreatine, and NAA expressed relative to control subjects with TD were examined to evaluate tissue compactness. Results The children with ASD demonstrated decreased gray matter concentrations of Cho ( P P = .02), NAA ( P = .02), and mI ( P = .008) compared with children with TD. Gray matter Cho transverse relaxation was also prolonged for the ASD sample compared with the TD group ( P = .01). The children with ASD demonstrated significantly decreased levels of Cho ( P = .04) and mI ( P = .008) and trend-level NAA ( P = .09) in gray matter compared with the DD group. For white matter, both children with ASD and children with DD showed a similar pattern of NAA and mI level decreases (for children with ASD vs children with TD: NAA, P = .03; mI, P = .04; for children with DD vs children with TD, NAA, P = .03; mI, P = .07). In several analyses, cerebral volume contributed significantly as a covariate. Conclusions Reduced gray matter chemical concentrations and altered Cho transverse relaxation, in a pattern distinct from that in children with DD, suggest decreased cellularity, or density, at this early time point in ASD. Possibly reflecting shared developmental features, white matter results were common to ASD and DD groups. The relationship between cerebral volume and neurochemistry at this early time point may indicate processes related to unit scaling.

Context The amygdala is associated with socioemotional function and has been implicated in the pathophysiology of autism. Objective To examine the relationship between amygdalar volume at ages 3 and 4 years and severity of clinical course and outcome at 6 years of age in children with autism spectrum disorder. Design Magnetic resonance images acquired at 3 and 4 years of age were used to measure total cerebral, amygdalar, and hippocampal volumes. Acquisition of social and communication skills was assessed semiannually using the Vineland Adaptive Behavior Scales. Hierarchical linear models were used to predict variability in individual linear growth trajectories as a function of IQ, total cerebral, and amygdalar or hippocampal volumes. Setting Longitudinal study of children with autism spectrum disorder. Participants Forty-five children with autism spectrum disorders between 3 and 6 years of age. Main Outcome Measure Linear growth trajectory of age equivalence Vineland communication and social scores. Results Larger right amygdalar volume was associated with more severe social and communication impairments at ages 3 and 4 years. Larger right amygdalar volume also was predictive of poorer social and communication abilities at age 6 years, even after controlling for IQ and total cerebral volume. Parallel analyses with hippocampal volumes found no relationship to social or communication development. Conclusions Larger right amygdalar volume at 3 and 4 years of age, but not left amygdalar, hippocampal, or total cerebral volume, is associated with a more severe clinical course and worse outcome at age 6 years in children with autism spectrum disorder. These results provide additional evidence that amygdalar development is implicated in the behavioral impairments found in autism.