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Amygdala Enlargement in Toddlers with Autism Related to Severity of Social and Communication Impairments

Published:September 03, 2009DOI:https://doi.org/10.1016/j.biopsych.2009.07.007

      Background

      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.

      Methods

      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 ∼5 years of age for final clinical evaluation.

      Results

      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.

      Conclusions

      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.

      Key Words

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      References

        • Adolphs R.
        Fear, faces, and the human amygdala.
        Curr Opin Neurobiol. 2008; 18: 166-172
        • Dawson G.
        • Meltzoff A.N.
        • Osterling J.
        • Rinaldi J.
        Neuropsychological correlates of early symptoms of autism.
        Child Dev. 1998; 69: 1276-1285
        • Werner E.
        • Dawson G.
        • Osterling J.
        • Dinno N.
        Brief report: Recognition of autism spectrum disorder before one year of age: A retrospective study based on home videotapes.
        J Autism Dev Disord. 2000; 30: 157-162
        • American Psychiatric Association
        Diagnostic and Statistical Manual of Mental Disorders.
        4th ed. American Psychiatric Association, Washington, DC1994
        • Amaral D.G.
        • Schumann C.M.
        • Nordahl C.W.
        Neuroanatomy of autism.
        Trends Neurosci. 2008; 31: 137-145
        • DiCicco-Bloom E.
        • Lord C.
        • Zwaigenbaum L.
        • Courchesne E.
        • Dager S.R.
        • Schmitz C.
        • et al.
        The developmental neurobiology of autism spectrum disorder.
        J Neurosci. 2006; 26: 6897-6906
        • Bishop S.J.
        Neurocognitive mechanisms of anxiety: An integrative account.
        Trends Cogn Sci. 2007; 11: 307-316
        • Pitkanen A.
        • Tuunanen J.
        • Kalviainen R.
        • Partanen K.
        • Salmenpera T.
        Amygdala damage in experimental and human temporal lobe epilepsy.
        Epilepsy Res. 1998; 32: 233-253
        • Schumann C.M.
        • Amaral D.G.
        The human amygdala and autism.
        in: Whalen P. Phelps E. The Human Amygdala. Guilford Press, New York2009
        • Schumann C.M.
        • Hamstra J.
        • Goodlin-Jones B.L.
        • Lotspeich L.J.
        • Kwon H.
        • Buonocore M.H.
        • et al.
        The amygdala is enlarged in children but not adolescents with autism; the hippocampus is enlarged at all ages.
        J Neurosci. 2004; 24: 6392-6401
        • Mosconi M.W.
        • Cody-Hazlett H.
        • Poe M.D.
        • Gerig G.
        • Gimpel-Smith R.
        • Piven J.
        Longitudinal study of amygdala volume and joint attention in 2- to 4-year-old children with autism.
        Arch Gen Psychiatry. 2009; 66: 509-516
        • Sparks B.F.
        • Friedman S.D.
        • Shaw D.W.
        • Aylward E.
        • Echelard D.
        • Artru A.A.
        • et al.
        Brain structural abnormalities in young children with autism spectrum disorder.
        Neurology. 2002; 59: 184-192
        • Haznedar M.M.
        • Buchsbaum M.S.
        • Wei T.C.
        • Hof P.R.
        • Cartwright C.
        • Bienstock C.A.
        • et al.
        Limbic circuitry in patients with autism spectrum disorders studied with positron emission tomography and magnetic resonance imaging.
        Am J Psychiatry. 2000; 157: 1994-2001
        • Aylward E.H.
        • Minshew N.J.
        • Goldstein G.
        • Honeycutt N.A.
        • Augustine A.M.
        • Yates K.O.
        • et al.
        MRI volumes of amygdala and hippocampus in non-mentally retarded autistic adolescents and adults.
        Neurology. 1999; 53: 2145-2150
        • Nacewicz B.M.
        • Dalton K.M.
        • Johnstone T.
        • Long M.T.
        • McAuliff E.M.
        • Oakes T.R.
        • et al.
        Amygdala volume and nonverbal social impairment in adolescent and adult males with autism.
        Arch Gen Psychiatry. 2006; 63: 1417-1428
        • Pierce K.
        • Müller R.-A.
        • Ambrose J.
        • Allen G.
        • Courchesne E.
        Face processing occurs outside the fusiform “face area” in autism: Evidence from fMRI.
        Brain. 2001; 124: 2059-2073
        • Giedd J.N.
        Normal development.
        Child Adolesc Psychiatr Clin North Am. 1997; 6: 265-282
        • Giedd J.N.
        • Snell J.W.
        • Lange N.
        • et al.
        Quantitative magnetic resonance imaging of human brain development: Ages 4–18.
        Cerebral Cortex. 1996; 6: 551-560
        • Courchesne E.
        • Karns C.M.
        • Davis H.R.
        • Ziccardi R.
        • Carper R.A.
        • Tigue Z.D.
        • et al.
        Unusual brain growth patterns in early life in patients with autistic disorder: An MRI study.
        Neurology. 2001; 57: 245-254
        • Courchesne E.
        • Pierce K.
        • Schumann C.M.
        • Redcay E.
        • Buckwalter J.A.
        • Kennedy D.P.
        • et al.
        Mapping early brain development in autism.
        Neuron. 2007; 56: 399-413
        • Mullen E.M.
        Mullen Scales of Early Learning.
        American Guidance Service, Circle Pines, MN1995
        • DiLavore P.C.
        • Lord C.
        • Rutter M.
        The pre-linguistic autism diagnostic observation schedule.
        J Autism Dev Disorders. 1995; 25: 355-379
        • Lord C.
        • Risi S.
        • Lambrecht L.
        • Cook Jr, E.
        • Leventhal B.
        • DiLavore P.
        • et al.
        The Autism Diagnostic Observation Schedule—Generic: A standard measure of social and communication deficits associated with the spectrum of autism.
        J Autism Dev Disorders. 2000; 30: 205-223
        • Lord C.
        • Rutter M.
        • Le Couteur A.
        Autism Diagnostic Interview—Revised: A revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders.
        J Autism Dev Disorders. 1994; 24: 659-685
        • Wechsler D.
        Wechsler Preschool and Primary Scale of Intelligence—III.
        Psychological Corporation, San Antonio, TX2002
        • Sparrow S.
        • Balla D.
        • Cicchetti D.
        Vineland Scales of Adaptive Behavior: Survey Form Manual.
        American Guidance Service, Circle Pines, MN1984
        • Carper R.A.
        • Moses P.
        • Tigue Z.D.
        • Courchesne E.
        Cerebral lobes in autism: Early hyperplasia and abnormal age effects.
        Neuroimage. 2002; 16: 1038-1051
        • Courchesne E.
        • Karns C.
        • Davis H.R.
        • Ziccardi R.
        • Carper R.
        • Tigue Z.
        • et al.
        Unusual brain growth patterns in early life in patients with autistic disorder: An MRI study.
        Neurology. 2001; 57: 245-254
        • Egaas B.
        • Courchesne E.
        • Saitoh O.
        Reduced size of corpus callosum in autism.
        Arch Neurol. 1995; 52: 794-801
        • Robb R.A.
        • Hanson D.P.
        • Karwoski R.A.
        • Larson A.G.
        • Workman E.L.
        • Stacy M.C.
        Analyze: A comprehensive, operator-interactive software package for multidimensional medical image display and analysis.
        Comput Med Imaging Graph. 1989; 13: 433-454
        • Akshoomoff N.
        • Lord C.
        • Lincoln A.
        • Courchesne R.Y.
        • Carper R.
        • Townsend J.
        • et al.
        Outcome classification of preschool children with autism spectrum disorders using MRI brain measures.
        J Am Acad Child Adolesc Psychiatry. 2004; 43: 349-357
        • Bloss C.S.
        • Courchesne E.
        MRI neuroanatomy in young girls with autism: A preliminary study.
        J Am Acad Child Adolesc Psychiatry. 2007; 46: 515-523
        • Munson J.
        • Dawson G.
        • Abbott R.
        • Faja S.
        • Webb S.J.
        • Friedman S.D.
        • et al.
        Amygdalar volume and behavioral development in autism.
        Arch Gen Psychiatry. 2006; 63: 686-693
        • Pinter J.D.
        • Brown W.E.
        • Eliez S.
        • Schmitt J.E.
        • Capone G.T.
        • Reiss A.L.
        Amygdala and hippocampal volumes in children with Down's syndrome: A high-resolution MRI study.
        Neurology. 2001; 56: 972-974
        • Zeegers M.
        • Pol H.H.
        • Durston S.
        • Nederveen H.
        • Schnack H.
        • Daalen E.V.
        • et al.
        No differences in MR-based volumetry between 2- and 7-year-old children with autism spectrum disorder and developmental delay.
        Brain Dev. 2008; ([published online ahead of print Dec 8])
        • Mosconi M.W.
        • Hazlett H.C.
        • Poe M.D.
        • Gerig G.
        • Smith R.G.
        • Piven J.
        A longitudinal study of amygdala volume and joint attention in 2–4 year old children with autism.
        Arch Gen Psychiatry. 2009; 66: 509-516
        • Pierce K.
        • Haist F.
        • Sedaghat F.
        • Courchesne E.
        The brain response to personally familiar faces in autism: Findings of fusiform activity and beyond.
        Brain. 2004; 127: 2703-2716
        • Schultz R.T.
        Developmental deficits in social perception in autism: The role of the amygdala and fusiform face area.
        Int J Dev Neurosci. 2005; 23: 125-141
        • Osterling J.
        • Dawson G.
        Early recognition of children with autism: A study of first birthday home videotapes.
        J Autism Dev Disord. 1994; 24: 247-257
        • Klin A.
        • Jones W.
        • Schultz R.
        • Volkmar F.
        • Cohen D.
        Visual fixation patterns during viewing of naturalistic social situations as predictors of social competence in individuals with autism.
        Arch Gen Psychiatry. 2002; 59: 809-816
        • Pelphrey K.A.
        • Sasson N.J.
        • Reznick J.S.
        • Paul G.
        • Goldman B.D.
        • Piven J.
        Visual scanning of faces in autism.
        J Autism Dev Disord. 2002; 32: 249-261
        • Dalton K.M.
        • Nacewicz B.M.
        • Johnstone T.
        • Schaefer H.S.
        • Gernsbacher M.A.
        • Goldsmith H.H.
        • et al.
        Gaze fixation and the neural circuitry of face processing in autism.
        Nat Neurosci. 2005; 8: 519-526
        • Spezio M.L.
        • Adolphs R.
        • Hurley R.S.
        • Piven J.
        Abnormal use of facial information in high-functioning autism.
        J Autism Dev Disord. 2007; 37: 929-939
        • Kleinhans N.M.
        • Johnson L.C.
        • Richards T.
        • Mahurin R.
        • Greenson J.
        • Dawson G.
        • et al.
        Reduced neural habituation in the amygdala and social impairments in autism spectrum disorders.
        Am J Psychiatry. 2009; 166: 467-475
        • Amaral D.G.
        • Price J.L.
        Amygdalocortical projections in the monkey (Macaca fascicularis).
        J Comp Neurol. 1984; 230: 465-496
        • Johnson M.H.
        • Dziurawiec S.
        • Ellis H.
        • Morton J.
        Newborns' preferential tracking of face-like stimuli and its subsequent decline.
        Cognition. 1991; 40: 1-19
        • Adolphs R.
        The neurobiology of social cognition.
        Curr Opin Neurobiol. 2001; 11: 231-239