Endophenotype, Molecular Genetic Study on Attention-Deficit/Hyperactivity Disorder
Recruitment status was: Recruiting
Attention Deficit Hyperactivity Disorder
|Study Design:||Observational Model: Family-Based|
|Official Title:||Endophenotype, Molecular Genetic Study on Attention-deficit/ Hyperactivity Disorder|
|Study Start Date:||August 2007|
|Estimated Study Completion Date:||August 2010|
Attention deficit hyperactivity disorder (ADHD), characterized by inattention, hyperactivity and impulsivity, is an early onset, highly heritable, clinically heterogeneous, long-term impairing disorder with tremendous impact on individuals, families, and societies. It affects 5-10% of school-aged children worldwide (7.5% in Taiwan) and 2-4% of adults. Neuropsychological deficits related to executive functions, state regulation, and delay aversion show heritability, replicated association with ADHD, and familial-genetic overlap with ADHD, are suitable for biomarkers for ADHD. Despite the abundance of molecular genetic studies on ADHD, the genetic etiologies of ADHD have been non-conclusive, and there is limited information about the expressions, endophenotypes, and genetic variants for ADHD in Chinese population. This polite study, a family-based parental control association study, aims to identify the genetic markers for ADHD using the dichotomous categorization of affected and non-affected, quantitative phenotypes (symptoms dimension and severity of ADHD) and endophenotype (neuropsychological measures) as well.
- to determine the components of ADHD and neuropsychological deficit with the greatest familial recurrence risks;
- to replicate studies with positive genetic findings from literature by performing candidate gene analysis such as DRD4, DAT1, DRD5, HTR1B, SNPA-25, 5-HTT, DBH, CHRNA4, CHRNA7 etc;
- to identify the potential genetic variants using haplotype tag SNPs for the following candidate genes, CHRNA4 and CHRNA7 and any updated genetic findings.
We will recruit 200 probands with ADHD, aged 7-18, and their parents (n = 400) and siblings (n= 150) in three years (50, 100, and 50 families with ADHD 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, CPT, CANTAB, and Time Perception Tasks. The DNA will be collected and analyzed. The transmission/disequilibrium test (TDT) and quantitative TDT will be used in data analysis.
We anticipate the establishment of clinical, neuropsychological, and genetic database of 200 ADHD families, completion of the screening of several candidate genes, and identification of potential genetic variants for ADHD, and determination of their association with ADHD diagnosis and symptoms and its endophenotype in a Taiwanese sample. The long-term objectives are to identify the behavioral phenotypes and endophenotypes that are close to the biological expression of genes underlying ADHD. The findings of different approaches to identify the genetic etiologies for ADHD in this pilot study should help us to determine the most promising approach for future molecular genetic study on ADHD.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00529906
|National Taiwan University Hospital|
|Principal Investigator:||Susan Shur-Fen Gau, MD, PhD||Dept of Psychiatry, National Taiwan University Hospital|