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The Association Between Executive Functions and Candidate Genes of Dopaminergic and Noradrenergic Systems in Attention Deficit Hyperactivity Disorder (ADHD)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified January 2010 by National Taiwan University Hospital.
Recruitment status was  Not yet recruiting
Sponsor:
Collaborator:
National Health Research Institutes, Taiwan
Information provided by:
National Taiwan University Hospital
ClinicalTrials.gov Identifier:
NCT01052753
First received: January 18, 2010
Last updated: January 19, 2010
Last verified: January 2010
  Purpose

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.


Condition
Attention Deficit Hyperactivity Disorder

Study Type: Observational
Official Title: The Association Between Executive Functions and Candidate Genes of Dopaminergic and Noradrenergic Systems in Attention-deficit Hyperactivity Disorder

Resource links provided by NLM:


Further study details as provided by National Taiwan University Hospital:

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.


Estimated Enrollment: 300
Study Start Date: August 2010
Estimated Study Completion Date: July 2013
Groups/Cohorts
ADHD group
Control group

Detailed Description:

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.

Specific Aims:

  1. To identify specific genetic polymorphism of candidate genes of dopaminergic and noradrenergic systems (e.g., DRD2, DRD4, DRD5, DAT1, NET, ADRA2A, DBH, COMT etc.) associated with executive dysfunctions measured by the CANTAB and other alternative phenotype approaches (ADHD subtypes, comorbidities, treatment effects, IQ, symptom dimensions and severity);
  2. to investigate the relationship between a variety of ADHD phenotypes and endophenotypes and gene expressions of DRD2, DAT1, NET, ADRA2A, DBH, and COMT;
  3. to validate executive functions and to search for other neuropsychological functioning as endophenotypes for ADHD; and
  4. to determine whether ADHD is familial and identify which core symptoms of ADHD and which component of neuropsychological functioning are most familial;

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.

  Eligibility

Ages Eligible for Study:   7 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

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.

Criteria

Inclusion Criteria:

  • The inclusion criteria for the proband subjects are (1) that subjects have a clinical diagnosis of ADHD, or Hyperkinetic Disorder (HD) defined by the DSM-IV and ICD-10, respectively, which was made by a full-time board-certificated child psychiatrist at the first visit and following visits; (2) their ages range from 7 to 18 when we conduct the study; (3) subjects who are able to perform the CANAB and time tests; (4) subjects' IQ greater than 80; (5) subjects have both biological parents; (6) both parents are Han Chinese; and (7) subjects and their biological parents (and siblings if any) consent to participate in this study for complete phenotype assessments and blood data collection.
  • The inclusion criteria for the control subjects are (1) that subjects who do not have the diagnosis of ADHD, or Hyperkinetic Disorder (HD) defined by the DSM-IV and ICD-10, respectively, in the past and current assessments; (2) subjects who are able to perform the CANAB and time tests; (4) subjects' IQ greater than 80; (5) subjects are Han Chinese; and (6) subjects and their mothers consent to participate in this study for complete phenotype assessments.

Exclusion Criteria:

  • The proband subjects will be excluded from the study if they currently meet criteria or have a history of the following condition as defined by DSM-IV: Schizophrenia, Schizoaffective Disorder, Organic Psychosis, or Pervasive Developmental Disorder. Moreover, the subjects will also be excluded from the study if they completely cannot cooperate with blood withdrawal or neuropsychological assessments.
  • The control subjects will be excluded from the study if they currently meet criteria or have a history of the following condition as defined by DSM-IV: Schizophrenia, Schizoaffective Disorder, Organic Psychosis, or Pervasive Developmental Disorder. Moreover, the subjects will also be excluded from the study if they completely cannot cooperate with neuropsychological assessments.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01052753

Contacts
Contact: Susan Shur-Fen Gau, MD, PhD +886-2-23123456 ext 66802 gaushufe@ntu.edu.tw

Locations
Taiwan
National Taiwan Univeristy Hospital Not yet recruiting
Taipei, Taiwan
Contact: Susan Shur-Fen Gau, MD, PhD    +886-2-23123456 ext 66802    gaushufe@ntu.edu.tw   
Principal Investigator: Susan Shur-Fen Gau, MD, PhD         
Sponsors and Collaborators
National Taiwan University Hospital
National Health Research Institutes, Taiwan
Investigators
Principal Investigator: Susan Shur-Fen Gau, MD, PhD National Taiwan University Hospital & College of Medicine
  More Information

No publications provided

Responsible Party: Susan Shur-Fen Gau, National Taiwan University Hospital
ClinicalTrials.gov Identifier: NCT01052753     History of Changes
Other Study ID Numbers: 200912118R
Study First Received: January 18, 2010
Last Updated: January 19, 2010
Health Authority: Taiwan: Department of Health

Keywords provided by National Taiwan University Hospital:
Attention-deficit/hyperactivity disorder
executive function
endophenotype
dopaminergic system
noradrenergic system
candidate gene
Family-based association study

Additional relevant MeSH terms:
Attention Deficit Disorder with Hyperactivity
Disease
Hyperkinesis
Attention Deficit and Disruptive Behavior Disorders
Dyskinesias
Mental Disorders
Mental Disorders Diagnosed in Childhood
Nervous System Diseases
Neurologic Manifestations
Pathologic Processes
Signs and Symptoms
Dopamine
Dopamine Agents
Dopamine Agonists
Autonomic Agents
Cardiotonic Agents
Cardiovascular Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Sympathomimetics
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2014