Behavior, Neuropsychology, Neuroimage and Electrophysiology in Autistic Individuals With and Without CNVs
Condition: Autism
MeSH terms: Autistic Disorder
Study type: Observational

Summary: 
      The study aims to investigate whether neuropsychological function (particularly cognitive
      flexibility and executive function), functional (assessed by resting functional MRI, rfMRI)
      and structural connectivity (assessed by DSI), and electrophysiological function (assessed by
      event-related potential [ERP]: mismatch negativity, MMN and P50) can be effective cognitive
      endophenotypes (biomarkers) for Autism spectrum disorders (ASD).
    

Detailed description: 
      Autism spectrum disorders (ASD) is a common severe, multi-factorial, highly heritable,
      clinically and genetically heterogeneous, life-long impairing childhood-onset
      neurodevelopmental disorder. Due to its high prevalence and severe lifelong impairment
      without effective prevention and pharmacological treatment, this disastrous disease has been
      prioritized for epidemiological, molecular genetic and biomarker studies in the world.

      Specific aims:

        1. To validate the structural and functional connectivity in fronto-temporal, and
           cortico-striato-thalamic circuitry as effective imaging endophenotypes by demonstrating
           the differences between ASD probands with CNVs findings (n=22) and their unaffected
           siblings (n=22), probands without CNVs and known genetic markers related to ASD (n=22)
           and their unaffected siblings (n=22), and matched neurotypicals (n=22 for each);

        2. To validate the neuropsychological functioning (particularly set-shifting and executive
           function) as effective neuropsychological endophenotypes by demonstrating the
           differences among the six groups;

        3. To validate the electrophysiological functioning assessed by ERP as effective
           neurophysiological endophenotypes by demonstrating the differences among the 6 groups;
           and

        4. To correlate the data from structural and functional connectivity, neuropsychology, and
           electrophysiology involving altered brain functioning.

      The investigators anticipate that probands with CNVs may have higher level of decreased
      structural and functional connectivity, impaired ERP and neuropsychological functioning than
      probands without CNVs. The alterations in the structural and functional connectivity,
      neurophysiological and neuropsychological functioning would be observed in the unaffected
      siblings as compared to neurotypical participants. If CNV in the probands is proved to be de
      novo mutation and their unaffected siblings did not have such results, the likelihood of
      different functioning between their unaffected siblings and neurotypical participants would
      be decreased. The genetic dosage (CNV, rare mutation with moderate to large clinical effect,
      versus multiple common variants with very small effects, with regards to unaffected siblings,
      and neurotypicals) is anticipated to pose the strongest effects on the microstructural
      integrity of white matter, followed by functional connectivity and electrophysiological
      function, and neuropsychological function with the least effect.
    

Observational model: Other
Time perspective: Other
Sampling method: Non-Probability Sample
Study population: 
        The sample (6 groups) consists of 44 individuals with clinical diagnosis of ASD confirmed
        by the ADI-R and ADOS assessments (22 with CNVs and 22 without CNVs), their unaffected
        siblings (n=22 for each group) and age-, sex-, handedness-, and IQ-matched school
        comparison groups (22 for each group).
      
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.