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Neuropsychopathological Study of Autism

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01677663
Recruitment Status : Unknown
Verified August 2012 by National Taiwan University Hospital.
Recruitment status was:  Recruiting
First Posted : September 3, 2012
Last Update Posted : September 3, 2012
National Taiwan University
Information provided by (Responsible Party):
National Taiwan University Hospital

Brief Summary:
Autism or autism spectrum disorder (ASD) is a relatively common (0.3% in Taiwan), multi-factorial, genetically and clinically heterogeneous, childhood-onset neurodevelopmental disorder. Due to its high heritability and severe long-term impairment without available laboratory diagnosis, effective prevention or treatment, this disastrous disease has been prioritized for molecular genetic studies. Recent CNVs investigation to identify rare variants and GWA study with endophenotype approaches are promising strategies to identify common genetic variants. In addition to intermediate phenotypes such as head circumstance, speech delay, social impairments and stereotyped behaviors, evidence has demonstrated that neuropsychology and neuroimages may be useful endophenotypes for autism. Dlgap2, Fbxo25, and Arhgef10 knoutout mice generated from our previous CNV results will be characterized.

Condition or disease

Detailed Description:

The specific aims of the study aree:

  1. To collect complete environmental, developmental, clinical, neuropsychological, and genetic data of 350 probands with autism (800 in total, 450 from [96HD008]) and their families;
  2. To re-sequence promoter region, all the exons, and the 3'UTR region of the DLGAP2, CLN8, ARHGEF10, FBXO25, and GABRB3 genes (one gene per year);
  3. To conduct fine-mapping and replication studies for selected candidate genes from GWA study[96HD008];
  4. To validate social impairment and speech delay as intermediate phenotypes and the executive functions as effective cognitive endophenotypes by first demonstrating the differences in these measures among probands, their unaffected siblings and neurotypicals, followed by different genetic risks (e.g., neurexin, neuroligin, CNTNAP2, SHANK3, MET, PTEN, WNT2, FOXP2, DLGAP2, CLN8, ARHGEF10, FBXO25, and GABRB3);
  5. To validate the structural and functional connectivity as effective imaging endophenotypes by demonstrating the differences between probands with autism, their siblings, and matched neurotypicals; and
  6. To characterize the phenotypes of and to explore the possible function of other autism-related genes found by using GWAS, and to explore the possible drug targets for the treatment for Dlgap2, Fbxo25, and Arhgef10 mutant mice.

The investigators will recruit 350 probands with clinical diagnosis of autism confirmed by the ADI-R and ADOS, and their families. The probands and their siblings will also be assessed for other psychiatric disorders (K-SADS-E); autistic symptom dimensions (SRS, SCQ, CAST, ABC), other behavioral symptoms (CBCL, SNAP-IV), and perinatal/environmental risk factors. The direct tests include intelligence (CPM/SPM, WISC-III, WPPSI-R) and neuropsychological tests (CPT, WCST, CANTAB). The parents will be assessed for DSM-IV psychiatric disorders (ASRI-4) and autistic features (AQ, SRS). The investigators will collect blood samples from all the subjects. Probands with previous CNVs findings (n = 20) and high-functioning autism (n=30) will receive the MRI assessments (Diffusion Spectrum Imaging, resting-state fMRI) as compared to 50 age-, sex-, and handedness-matched neurotypicals.

The investigators will (1) characterize the behavioral, structural, electrophysiological and biochemical phenotypes of Dlgap2, and Arhgef10 mice at 4 weeks, 8 weeks, 12 weeks and 16 weeks of ages; (2) explore the possible function of other autism-related genes found by GWAS analysis; and (3) explore the possible drug targets for the treatment of autism from KO mice. While the potential target is recognized, existing compounds of this target can be tested.

The investigators anticipate to establishing a representative cohort of 800 patients with autism and their families from this study and [96HD008] with comprehensive clinical and genetic data. This well-characterized cohort will contribute to validation of intermediate phenotypes and cognitive and imaging endophenotypes for autism in this study, and will be used to search for rare variants by CNVs analysis and common variants by GWAS analysis in future study, and will pave the way to have 2-3 lines of well-characterized transgenic animal models of autism (e.g., Dlgap2). In addition, a wealth of data from this cohort will benefit to current and future investigation on autism and will be the basis for future international collaboration. The investigators also anticipated to publication of 20 SCI papers (4 per year) and presentation of our work in peer-reviewed scientific conferences by more than 40 posters or oral communications.

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Study Type : Observational
Estimated Enrollment : 350 participants
Observational Model: Family-Based
Official Title: Neuropsychopathological Study of Autism: From Clinical, Neurocognitive, to Genetic Studies and Animal Models
Study Start Date : August 2011
Estimated Study Completion Date : July 2016

Biospecimen Retention:   Samples With DNA
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.

Information from the National Library of Medicine

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Ages Eligible for Study:   3 Years to 25 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
The sample will consist of 350 probands with ASD, aged 3-25.

Inclusion Criteria:

  • subjects have a clinical diagnosis of autistic disorder or Asperger disorder defined by the DSM-IV and ICD-10;
  • their ages range from 3 to 25 when we conduct the study;
  • subjects have at least one biological parent;
  • both parents of the subjects are Han Chinese;
  • subjects and their biological parents (and siblings if any) consent to participate in this study.

Exclusion Criteria:

  • if they currently meet criteria or have a history of DSM-IV Schizophrenia, Schizoaffective Disorder, or Organic Psychosis.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01677663

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Contact: Susan Shur-Fen Gau, MD, PhD 886-2-23123456 ext 66802

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National Taiwan Univeristy Hospital Recruiting
Taipei, Taiwan
Contact: Susan Shur-Fen Gau, MD, PhD    886-2-23123456 ext 66802   
Principal Investigator: Susan Shur-Fen Gau, MD, PhD         
Sub-Investigator: Wen-Mei Fu, PhD         
Sub-Investigator: Chia-Hsiang Chen, MD, PhD         
Sub-Investigator: Wen-Yih Isaac Tseng, MD, PhD         
Sub-Investigator: Po-Hsiu Kuo, PhD         
Sponsors and Collaborators
National Taiwan University Hospital
National Taiwan University
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Principal Investigator: Susan Shur-Fen Gau, MD, PhD National Taiwan University Hospital & College of Medicine
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Responsible Party: National Taiwan University Hospital, Susan Shur-Fen Gau Identifier: NCT01677663    
Other Study ID Numbers: 201103003RB
First Posted: September 3, 2012    Key Record Dates
Last Update Posted: September 3, 2012
Last Verified: August 2012
Keywords provided by National Taiwan University Hospital:
clinical phenotypes
imaging endophenotypes
family-based cohort
knoutout mice
Additional relevant MeSH terms:
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Autistic Disorder
Autism Spectrum Disorder
Child Development Disorders, Pervasive
Neurodevelopmental Disorders
Mental Disorders