Ignite Creation Date:
2024-05-06 @ 12:52 AM
Last Modification Date:
2024-10-26 @ 10:56 AM
Study NCT ID:
NCT01677663
Status:
UNKNOWN
Last Update Posted:
2012-09-03
First Post:
2012-08-30
Brief Title:
Neuropsychopathological Study of Autism
Sponsor:
National Taiwan University Hospital
Organization:
National Taiwan University Hospital
Study Overview
Official Title:
Neuropsychopathological Study of Autism From Clinical Neurocognitive to Genetic Studies and Animal Models
Status:
UNKNOWN
Status Verified Date:
2012-08
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Autism or autism spectrum disorder ASD is a relatively common 03 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
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 3UTR 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 study96HD008
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 eg 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 perinatalenvironmental risk factors The direct tests include intelligence CPMSPM 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 n30 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 eg 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
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 3UTR 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 study96HD008
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 eg 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 perinatalenvironmental risk factors The direct tests include intelligence CPMSPM 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 n30 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 eg 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None