The Association Between Executive Functions and Candidate Genes of Dopaminergic and Noradrenergic Systems in Attention Deficit Hyperactivity Disorder (ADHD)
Recruitment status was Not yet recruiting
|First Received Date ICMJE||January 18, 2010|
|Last Updated Date||January 19, 2010|
|Start Date ICMJE||August 2010|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE||Not Provided|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||Complete list of historical versions of study NCT01052753 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||The Association Between Executive Functions and Candidate Genes of Dopaminergic and Noradrenergic Systems in Attention Deficit Hyperactivity Disorder (ADHD)|
|Official Title ICMJE||The Association Between Executive Functions and Candidate Genes of Dopaminergic and Noradrenergic Systems in Attention-deficit Hyperactivity Disorder|
The ultimate goal of this study is to find specific polymorphism of candidate genes (particularly of dopaminergic and noradrenergic systems) associated with intermediate phenotypes (e.g., executive functions, IQ, and other neuropsychological function) and/or phenomenological phenotypes (subtypes, comorbidity, dimensional approach) of ADHD. We propose to replicate the analysis of the candidate genes identified by previous genetic studies and recent findings from GWAS on ADHD using the candidate gene association study design (family-based case control study using parental controls and population-based case-control study). These results may lead our research team: (1) to resolve controversies over inconsistent findings in previous genetic studies and contribute to the literature on the validity of ADHD and its subtypes using clinical and genetic data; (2) to identify potential endophenotypes for ADHD genetic studies; and (3) to identify specific polymorphism of candidate genes and gene expressions of dopaminergic and noradrenergic systems associated with executive functions measured by the CANTAB.
Attention deficit hyperactivity disorder (ADHD) is a common, impairing, highly heritable, clinically heterogeneous early-onset neuropsychiatric disorder. Despite substantial evidence supporting genetic etiology of ADHD, molecular genetic studies so far have not yet provided any conclusive results using the categorical or subgroup approach of phenotype. Hence, there has been growing interest in using endophenotypes in molecular genetic studies on ADHD. Our previous studies have demonstrated significant deficits in executive functions among children with ADHD and the efficacy of methylphenidate and atomoxetine, involving dopaminergic and noradrenergic systems, in reducing ADHD core symptoms and improving executive functions. In a longitudinal follow-up family study on ADHD, we also reported that executive dysfunctions measured by the Cambridge Neuropsychological Test Automated Batteries (CANTAB) are potential endophenotypes for ADHD. Hence, identifying specific polymorphism of candidate genes of dopaminergic and noradrenergic systems associated with executive dysfunctions in Han Chinese in Taiwan is warranted.
Subjects and Methods: The major study design is the family-based case-control candidate gene association study. We will recruit 150 probands with ADHD, aged 7-18, and their parents (n = 300) and siblings (n= 150) and 150 school controls in three years (50, 60, and 40 families with ADHD and 50, 60, 40 school controls in the 1st, 2nd, and 3rd year, respectively). The measures include (1) interviews for psychopathology (K-SADS-E) and social functioning (SAICA), (2) self-administered questionnaires to measures ADHD symptoms (CPRS-R:S, CTRS-R:S, SNAP-IV and Adult ADHD rating scale) and comorbid conditions (ASRI and CBCL), and (3) neuropsychological tests: WISC-III-R, CPT, CANTAB, and Time Perception Tasks. The transmission/disequilibrium test (TDT) and quantitative TDT by using FBAT and FBAT-GEE, GEE, and Mixed Models will be used for data analysis.
Anticipated Results: We anticipate the establishment of clinical, neuropsychological, and genetic database of at least 350 families (150 families in this project) and 150 same-age controls, the completion of genetic analysis and gene expressions of several candidate genes including those involving dopaminergic and noradrenergic systems, and identification of genetic variants for ADHD diagnosis, symptoms, and comorbidities, executive functions, and other neurocognitive endophenotypes in a Taiwanese sample. The findings of different approaches to identify the genetic etiologies for ADHD in this study should help us determine the most promising approach for future molecular genetic studies on ADHD.
|Study Type ICMJE||Observational|
|Study Design ICMJE||Not Provided|
|Target Follow-Up Duration||Not Provided|
|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.
|Sampling Method||Non-Probability Sample|
The proband sample will consist of at least 150 drug-naïve children and adolescents with ADHD, aged 7-18 (who are able to perform the CANTAB and time tasks) from Department of Psychiatry, National Taiwan University Hospital (NTUH). Their biological parents (n = 300) and siblings (estimated number = 150) born to the same biological parents will be recruited as the parent controls and sibling controls, respectively, for the family-based case control study. We will recruit 150 school controls without lifetime diagnosis of ADHD in the same school districts and with similar age and gender distributions of the probands with ADHD.
|Condition ICMJE||Attention Deficit Hyperactivity Disorder|
|Intervention ICMJE||Not Provided|
|Study Group/Cohort (s)||
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Not yet recruiting|
|Estimated Enrollment ICMJE||300|
|Estimated Completion Date||July 2013|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
|Ages||7 Years to 18 Years|
|Accepts Healthy Volunteers||Yes|
|Location Countries ICMJE||Taiwan|
|NCT Number ICMJE||NCT01052753|
|Other Study ID Numbers ICMJE||200912118R|
|Has Data Monitoring Committee||Yes|
|Responsible Party||Susan Shur-Fen Gau, National Taiwan University Hospital|
|Study Sponsor ICMJE||National Taiwan University Hospital|
|Collaborators ICMJE||National Health Research Institutes, Taiwan|
|Information Provided By||National Taiwan University Hospital|
|Verification Date||January 2010|
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