Autism Research Projects

NIH Autism Centers of Excellence - ACE Imaging Network

A Longitudinal MRI Study of Infants at Risk for Autism ( IBIS – Infant Brain Imaging Study www.ibis-network.org )

This is an Autism Centers of Excellence (ACE) Network Imaging study that is a collaborative effort by investigators from the University of Washington, University of North Carolina, Washington University, and University of Pennsylvania (Children’s Hospital of Philadelphia) conducting longitudinal MRI/DTI and behavioral studies of infants at high risk for autism (i.e. siblings of autistic individuals) at 6, 12, and 24 months of age.  Additional supplental funding is allowing us to assess genetic contributions to brain development in those children who develop symptoms of autism disorder compared to at risk children who do not.

The aim of this project is to increase our understanding of brain development in autism with the overall goal of identifying risk markers for autism based on imaging measures and their relationships to variations in clinical course.  Evidence from head circumference studies including our own suggests that brain overgrowth in young children with autism is between 6 months and 12 months of age.  This study focuses on two pivotal time-points:

12 Mos. Children at high risk for Autism

For 12 month old infant siblings of children with autism who are at high risk for autism, and are expressing early symptoms, we are using structural and chemical imaging measures to characterize hypothesized brain developmental abnormalities.  These 12 month brain measures will be evaluated in relationship to the early course of autism symptom progression from 12 months to 2 years when the diagnosis of autism can be established.

13 - 15 Year old Children With Autism Spectrum Disorder, Developmental Disabilities with out Autism 

The second pivotal time point we are studying is adolescence, a period during which children with autism are at increased risk for behavioral decline and clinical onset of seizures.  We are extending longitudinal imaging studies to age 13 to 15 years for a unique sample of children with autism and match control samples of developmentally delayed and typically developing children previously imaged and evaluated at 3, 6, and 9 to 10 years of age.  At the 13 - 15 year old age range, approximately 15 to 25 percent of affected children are also at risk to develop seizures. 

The purpose of this study is to characterize brain anatomy and regional brain chemical composition in children with autism spectrum disorder (ASD) and developmental disorder (DD) in comparison to typically developing (TD) children using 3-D magnetic resonance imaging (MRI) and spectroscopic imaging (MRSI).  Image findings will be related to risk for seizure onset and psychiatric comorbidities.

The overall aim of this research continues to be better understanding of mechanisms underlying autism and developmental disorders, and ultimately to provide effective treatment interventions for these disorders.  Results from this work have been published in several journals. (see below)

Brain Development in Autism – Project IV

Autism Research Center of Excellence: The STAART Program

The objectives of this project are to characterize abnormalities of brain development in young children with autism and delayed development at as early an age as clinical diagnosis is possible to increase understanding of when and how such abnormalities are manifested.  We are using MRI / MRS measures to develop a brain based model for early prediction of symptom severity, clinical course, response to treatment and outcome.  Results from a previous study investigating brain structural differences in 3 – 4 year old children with autism differ in their pattern of structural brain abnormalities from children with fewer autism symptoms (PDD-NOS) and from DD children.

We are examining differences in brain structure and chemistry between children with AD and children with DD and TD at 18 to 24 months of age and assessing the relationship between individual differences in brain structure and chemistry with concurrent and longitudinal measures of symptom severity, IQ, language, social behavior, and neuropsychological functioning.

In addition we are examining whether brain MRI/MRS measures are predictors of response to early behavioral intervention.  We are also comparing head circumference growth trajectories of children with AD, DD, and TD retrospectively from birth up to 4 years of age and examining the relation between individual differences in patterns of head growth, MRI findings and variations in clinical course during the preschool years.  Results from this work have been published in several journals.

PUBLICATIONS: 

• Dager SR, Corrigan NM, Estes A, Shaw DW. Further Commentary on Mitochondrial Dysfunction in Autism Spectrum Disorder: Assessment and Treatment Considerations. J Autism Dev Disord. 2011 Aug 19. [Epub ahead of print] PMID: 21853372
  

• Corrigan NM, Shaw DWW, Richards TL, Estes A, Friedman SD, Petropoulos H, Artru AA, Dager SR. Proton magnetic resonance spectroscopy and MRI reveal no evidence for brain mitochondrial dysfunction in children with autism spectrum disorder. J Autism Dev Disord. 2011 Mar 15. [Epub ahead of print - PMID: 21404085

• Dager SR, Corrigan NM, Richards TL, Shaw DWW. Brain Chemistry: Magnetic Resonance Spectroscopy. In D. Amaral, G. Dawson, and D. Geshwind (Eds.), Autism Spectrum Disorders, Oxford University Press. 2011, pages 576- 59

• Estes A, Shaw DWW, Spark BF, Friedman S, Giedd JN, Dawson G, Bryan, M, Dager SR.  Basal Ganglia Morphometry and Repetitive Behavior in Young Children with Autism Spectrum Disorder. Autism Research, 4(3), 212-220, 2011.  PMCID: PMC3110551 PMID:21480545
  

• Kim JE, Lyoo IK, Estes AM, Renshaw PF, Shaw DW, Friedman SD, Kim DJ, Yoon SJ, Hwang J, Dager SR. Laterobasal Amygdalar Enlargement in 6- to 7-Year-Old Children with Autism Spectrum Disorder. Archives of General Psychiatry. 67(11):1187-97, 2010 PMID: 21041620
  

• Webb SJ, Sparks BF, Friedman SD, Shaw DW, Giedd J, Dawson G, Dager SR.  Cerebellar vermal volumes in children with Autism Spectrum Disorder.  Psychiatry Research: Neuroimaging Feb. 24 2009, PMID: 19243924 

• Dager SR, Friedman SD, Petropoulos, Shaw DWW.  Imaging evidence for pathological brain development in Autism Spectrum Disorders.  In Zimmerman A, ed. Autism: current theories and evidence.  Totowa (NJ): Humana Press. 361-379, 2009.
• Dager SR, Oskin NM, Richards TL, Posse S.  Research Applications of Magnetic Resonance Spectroscopy (MRS) to Investigate Psychiatric Disorders.  Topics in Magnetic Resonance Imaging. 19(2):81-96, 2008. PMID: 19363431
  
• Belmonte M, Mazziotta J, Minshew N, Evans A, Courchesne E, Dager S, Bookheimer S, Aylward E, Amaral D, Cantor R, Chugani D, Dale A, Davatzikos C, Gerig G, Herbert M, Lainhart J, Murphy D, Piven J, Reiss A, Schultz B, Zeffiro T, Levi-Pearl S, Lajonchere C, Colamarino S. Offering to Share: How to Put Heads Together in Autism Neuroimaging. J Autism and Developmental Disorders. 38 (1): 2-13, 2008. PMID 1734788

• Dager SR, Petropoulos H, Friedman SD, Shaw DWW: Gray Matter T2 relaxation abnormalities in Autism Spectrum Disorder (letter). Neurology 68:1237-1238, 2007.

• Dager SR, Wang L, Friedman S, Shaw DD, Sparks B, Artru A, Dawson G, Csernansky J:  Shape Mapping of the Hippocampus in Young Children with Autism.  Am Jr Neuroradiol 28(4):672-7, 2007.  PMID:  17416819
• Wassink TH, Hazlett HC, Epping EA, Arndt S, Dager SR, Schellenberg GD, Dawson G, Piven J: Cerebral Cortical Gray Matter Overgrowth and Functional Variation of the Serotonin Transporter Gene in Autism. Arch Gen Psych, 64(6): 709-717, 2007.  PMID  17548752
• DiCicco-Bloom E, Lord C, Zwaigenbaum L, Courchesne E, Dager SR, Schmitz C,Schultz R, Crawley J, Young L:  The Developmental Neurobiology of Autism Spectrum Disorder. J Neurosci 26(26):6897-906, 2006.  PMID:  16807320
• Munson J, Dawson G, Abbott R, Faja S, Webb SJ, Friedman SD, Shaw DD, Artru AA,Dager SR: Amygdalar Volume and Behavioral Development in Autism.  Arch Gen Psychiatry 63(6): 686-693, 2006. (featured in the 2007 progress report on brain research from the Dana Alliance for Brain Initiatives).  PMID:  16754842
• Friedman SD, Shaw DWW, Artru AA, Petropoulos H, Dawson G, Dager SR:  Gray and White Matter Brain Chemistry in Young Children with Autism. Arch Gen Psychiatry 63(7):786-794, 2006.  PMID: 16818868
• Petropoulos H, Friedman SD, Shaw DWW, Artru AA, Dawson G, Dager SR. T2 relaxometry reveals evidence for gray matter abnormalities in Autism Spectrum Disorder. Neurology 67(4):632-6, 2006.(featured in the 2007 progress report on brain research from the Dana Alliance for Brain Initiatives).
  PMID:  16924017
• Boger-Megiddo I, Shaw DW, Friedman S.D, Sparks BF, Artru AA, Giedd JN, Dawson G, Dager SR: Corpus Callosum Morphometrics in Young Children with Autism Spectrum Disorder. J Autism Developmental Disorders. 36(6):733-739, 2006.  PMID:  16625438
• Amundsen LB, Artru AA, Dager SR, Shaw DWW, Friedman SD, Sparks B, Dawson G: Propofol sedation for Longitudinal Pediatric Neuroimaging.  J Neurosurg Anesthesiol 17:180-192, 2005. PMID:  16184061
• Friedman SD, Shaw DW, Artru AA, Richards TL, Gardner J, Dawson G, Posse S, and Dager SR Regional Brain chemical alterations in young children with autism spectrum disorder Neurology, 60: 100 – 107, 2003.  PMID:  12525726
• Dawson G, Webb S, Schellenberg G, Dager SR, Friedman SD, Aylward E, Richards T:  Defining the Broader Phenotype of Autism:  Genetic, Brain, and Behavioral Perspectives.  Development and Psychopathology 14:581-611, 2002. (Reprinted: Advances in Research on Autism and Developmental Disorders. Seiwa Shoten, Tokyo, Japan 2003).
• Sparks BF, Friedman SD, Shaw DW, Aylward EH, Echelard D, Artru AA, Maravilla KR,Giedd JN, Munson J, Dawson G, Dager SR. Brain Structural Abnormalities in Young Children with Autism Spectrum Disorder.  Neurology, 59, 184-192, 2002.  PMID:  12136055

CAN - Cure Autism Now

Three-Dimensional Morphometry of the Hippocampus in Children with Autism

This study demonstrated the feasibility of applying automated 3-dimensional morphometric methods to measure discrete brain regions in children with autism.  The general goal of this research was to elucidate underlying brain mechanisms responsible for autism in the hope that this will eventually lead to more effective medical treatment of the disorder.  More specifically, we assessed hippocampal relationships to seizure risk and neuro-cognitive defects in these children.  For this study we performed 3-D morphometry of the hippocampus in 3 year old children, adapting methods developed and implemented at Washington University, St. Louis, MO, using an existing data base of high resolution MRI’s obtained as part of an NICHHD-funded research project, “Neuroimaging of Autism” that longitudinally studied children between 3 to 4 years of age and 7 to 10 years of age.

Findings from this research revealed characteristic deformations of the subicular region of the hippocampus that were highly correlated with deficits of neuro behavioral testing that specifically tapped this area of the brain.  Findings in these children were similar to hippocampal deformities observed in adults with partial complex epilepsy, of potential clinical interest as these children are at high risk for developing epilepsy as they grow into adolescence.

PUBLICATIONS:

Dager SR, Wang L, Friedman S, Shaw DD, Sparks B, Artru A, Dawson G, Csernansky J: Shape Mapping of the Hippocampus in Young Children Autism.  Am J Neuroradial. 28(4):672-677, 2007.  PMID: 17416819