Structural Connectivity as Imaging Endophenotypes of Autism Spectrum Disorders
Condition: Autism Spectrum Disorders
MeSH terms: Autistic Disorder; Autism Spectrum Disorder; Child Development Disorders, Pervasive
Study type: Observational

Summary: 
      Autism spectrum disorders (ASD) is a highly hereditary neuropsychiatric disorder. In children
      and adolescents worldwide, the prevalence of ASD is estimated at 0.6%. Understanding the
      biological mechanism of this disorder could potentially facilitate prompt, accurate and
      personalized therapy. The dysfunction of fronto-temporal circuitry may explain language
      impairment in ASD. In addition, pieces of evidence suggest that the abnormality of the
      cortico-striato-thalamic circuitry might be related to social deficits. However, very little
      is known how changes in these two circuitries are related to variation in genotypes. Previous
      reports on ASD using magnetic resonance imaging (MRI) have demonstrated alteration of brain
      structure. Recent advance in neuroimaging has shown that structural connectivity of a
      specific circuitry is superior to regional analysis in terms of higher penetrance of genetic
      effects and better account for behavioral variance. Therefore, it is plausible that
      connectivity imaging may serve as effective endophenotypes that link clinical manifestation
      (phenotypes) and the biological variables (genotypes). In the past five years, our lab has
      established world leading diffusion spectrum imaging techniques, and applied the techniques
      to clinical studies on ASD, schizophrenia, stroke and epilepsy. The clinical experience and
      technical strengths provide a strong basis for us to extend to imaging genetics, aiming to
      determine effective endophenotypes of ASD. Therefore, the goal of this project is to validate
      structural connectivity of fronto-temporal and cortico-striato-thalamic circuitries as
      effective imaging endophenotypes of ASD. Specifically, the investigators will achieve the
      goal through a series of validation. First, the investigators will demonstrate that
      structural connectivities in the two targeted circuitries are indeed different among groups
      of patients with ASD, unaffected siblings, and neurotypicals. Second, the investigators will
      demonstrate in neurotypicals and unaffected siblings that the altered structural
      connectivities related to social and language impairments are indeed different in carriers of
      risk genes, i.e. CNTNAP2 and SLC25A12, respectively. Last, the investigators will demonstrate
      in all participants that the altered structural connectivities are associated with the
      corresponding behavioral variances in social and language function. This two-year project is
      a cohort study consisting of three groups, namely patient, unaffected siblings, and control
      groups matched in age, gender and handedness. The patient and sibling groups consist of 20
      boys each, age 10-15 years old, and the control group consists of 40 boys. The examination
      includes behavior assessment (IQ test, neuropsychological and clinical assessment), MRI study
      (structure MRI and diffusion spectrum imaging for structural connectivity) and genome
      scan(specifically candidate genes related to language function, i.e. SLC25A12, and to social
      function, i.e. CNTNAP2). In conclusion, this is the first cohort project on imaging genetics
      in Taiwan. The success of this project will facilitate the progress of translational
      neuroscience in Taiwan. The methodology of validating endophenotype will be readily extended
      to other psychiatric diseases.
    


Observational model: Cohort
Time perspective: Retrospective
Sampling method: Probability Sample
Study population: 
        High-functioning autism group,family group, and neurotypical group
      
Keywords: Autism spectrum disorders; structural connectivity; diffusion spectrum imaging; sibling; endophenotype