Behavior, Neuropsychology, Neuroimage and Electrophysiology in Autistic Individuals With and Without CNVs

NCT ID: NCT01582256

Last Updated: 2021-09-02

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 132 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2012-08-01
• Study Completion Date: 2015-07-31

Brief 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.

Conditions

Autism

Study Design

• Observational Model Type: OTHER
• Study Time Perspective: OTHER

Study Groups

ASD+CNVs

No interventions assigned to this group

ASD-CNVs

No interventions assigned to this group

Unaffected siblings of ASD+CNVs

No interventions assigned to this group

Unaffected siblings of ASD-CNVs

No interventions assigned to this group

Neurotypicals for ASD+CNVs comparisons

No interventions assigned to this group

Neurotypicals for ASD-CNVs comparisons

No interventions assigned to this group

Eligibility Criteria

Exclusion Criteria

2. their ages range from 10 to 25 (because all the probands with CNV aged > 10);

3. both parents are Han Chinese; and

4. subjects and their parents consent to participate in this study for complete phenotype assessments (3 visits of assessments).

• if they currently meet criteria or have a history of the following condition as defined by DSM-IV: Schizophrenia, Schizoaffective Disorder, or Organic Psychosis.

• Minimum Eligible Age: 10 Years
• Maximum Eligible Age: 25 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Taiwan University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Statistical Center, NTUHCTC

Susan Shur-Fen Gau

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Susan Shur-Fen Gau, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

National Taiwan University Hospital & College of Medicine

Locations

National Taiwan Univeristy Hospital

Taipei, , Taiwan

Countries

Taiwan

References

Chien YL, Chen YC, Chiu YN, Tsai WC, Gau SS. A translational exploration of the effects of WNT2 variants on altered cortical structures in autism spectrum disorder. J Psychiatry Neurosci. 2021 Dec 3;46(6):E647-E658. doi: 10.1503/jpn.210022. Print 2021 Nov-Dec.

Reference Type: DERIVED

PMID: 34862305 (View on PubMed)

Seng GJ, Tseng WL, Chiu YN, Tsai WC, Wu YY, Gau SS. Executive functions in youths with autism spectrum disorder and their unaffected siblings. Psychol Med. 2021 Nov;51(15):2571-2580. doi: 10.1017/S0033291720001075. Epub 2020 Apr 30.

Reference Type: DERIVED

PMID: 32349803 (View on PubMed)

Chien YL, Chou MC, Chiu YN, Chou WJ, Wu YY, Tsai WC, Gau SS. ADHD-related symptoms and attention profiles in the unaffected siblings of probands with autism spectrum disorder: focus on the subtypes of autism and Asperger's disorder. Mol Autism. 2017 Jul 25;8:37. doi: 10.1186/s13229-017-0153-9. eCollection 2017.

Reference Type: DERIVED

PMID: 28770037 (View on PubMed)

Chien YL, Tu EN, Gau SS. School Functions in Unaffected Siblings of Youths with Autism Spectrum Disorders. J Autism Dev Disord. 2017 Oct;47(10):3059-3071. doi: 10.1007/s10803-017-3223-0.

Reference Type: DERIVED

PMID: 28685410 (View on PubMed)

Chiang HL, Chen YJ, Lin HY, Tseng WI, Gau SS. Disorder-Specific Alteration in White Matter Structural Property in Adults With Autism Spectrum Disorder Relative to Adults With ADHD and Adult Controls. Hum Brain Mapp. 2017 Jan;38(1):384-395. doi: 10.1002/hbm.23367. Epub 2016 Sep 15.

Reference Type: DERIVED

PMID: 27630075 (View on PubMed)

Other Identifiers

201201006RIB

Identifier Type: -

Identifier Source: org_study_id