Structural and Functional Connectivity in Autism Spectrum Disorders
Condition: Autism Spectrum Disorder
MeSH terms: Autistic Disorder; Autism Spectrum Disorder; Child Development Disorders, Pervasive
Study type: Observational

Summary: 
      Autism spectrum disorder (ASD) has been given a high priority for genetic and neurobiological
      study. There is no such information in Asian population and no study has conducted using
      Diffusion Spectrum Imaging (DSI) to investigate the connectivity throughout the world.
      Moreover, no follow-up study has been done to examine the developmental changes of structural
      and functional connectivity. We anticipate to establishing a cohort of 50 ASD and their
      siblings with complete clinical, neuropsychological, brain imaging, and genetic data for
      longitudinal study on ASD. Our findings will contribute to our understanding of the
      structural and functional dysconnectivity for ASD and whether dysconnectivity can be an
      endophenotype for ASD and used as a biomarker for early diagnosis of ASD.
    

Detailed description: 
      Autism spectrum disorder (ASD) is a pervasive neuro-developmental disorder with prominent
      reciprocal social and communication impairment and restricted repetitive behavior or
      interest. Because ASD runs in family, because there is no effective biological treatment, and
      because early intervention can lead to better outcomes, ASD has been given a high priority
      for genetic and neurobiological study. Although abnormal brain structure has been reported,
      there is limited data regarding structural and functional dysconnectivity in autism. There is
      no such information in Asian population and no study has conducted using Diffusion Spectrum
      Imaging (DSI) to investigate the connectivity throughout the world. Moreover, no follow-up
      study has been done to examine the developmental changes of structural and functional
      connectivity. We thus propose this prospectively follow-up brain imaging study on ASD.

      Specific Aims:

        1. To investigate the location and extend of structural and functional dysconnectivity and
           their changes over a 2-year period among children with ASD, as compared to their
           unaffected siblings and normal controls;

        2. To correlate the structural and functional dysconnectivity to clinical severity and
           neuropsychological functioning;

        3. To test the association between brain dysconnectivity and several candidate genes
           related to the CNS patterning (e.g., RELN, En-2, Wnt, bcl-2); and

        4. To test whether neuropsychological and brain imaging findings can be the intermediate
           phenotype of ASD for genetic studies.

      We will recruit 50 children with DSM-IV ASD (autistic disorder and Asperger's disorder) aged
      3-15, their siblings, and 50 age-, sex-, and handedness-matached healthy controls. A number
      of instruments will be used to measure autistic symptoms, functional levels, and cognitive
      ability (i.e. ADI-R, ADOS, SCQ, SRS, and CAST; WISC-III (WPPSI-R, Bayley), DDST, CPM, and
      SPM; CPT, WCST, Cambridge Neuropsychological Test Automated Batteries). We will also look
      directly at the brain for structural and functional connectivity using the DSI and fMRI,
      respectively. We will repeat the assessments at a 2-year interval. The major tasks consisted
      of five parts: (1) 3 months-recruitment of subjects, researcher training, and pilot study;
      (2) 1 years 6 months-clinical, neuropsychological, genetic, DSI and fMRI assessments of 150
      subjects; (3) 6 months-data analysis, reports to subjects, and manuscript preparation; (4) 1
      years 6 months-same assessment of 150 subjects at a 2-year interval; (5) 4 months-data
      analysis, reports to subjects, and manuscript preparation.

      We anticipate to establishing a cohort of 50 ASD and their siblings with complete clinical,
      neuropsychological, brain imaging, and genetic data for longitudinal study on ASD. Our
      findings will contribute to our understanding of the structural and functional
      dysconnectivity for ASD and whether dysconnectivity can be an endophenotype for ASD and used
      as a biomarker for early diagnosis of ASD.
    

Observational model: Cohort
Time perspective: Other
Sampling method: Non-Probability Sample
Study population: 
        The sample will consist of 50 children with DSM-IV ASD (autistic disorder and Asperger's
        disorder) aged 3-15, their siblings, and 50 age-, sex-, and handedness-matached healthy
        controls.
      
Biospecimen description: 
      The subjects will receive blood withdrawal. The blood sample will be used for establishing
      lymphoblastoid cell lines, which will be used for molecular genetic experiments.
    
Keywords: autism spectrum disorders (ASD); structural and functional connectivity; diffusion spectrum imaging (DSI); functional magnetic resonance imaging (fMRI); siblings; repeated follow-up measurement