Structural and Functional Connectivity of Frontostriatal and Frontoparietal Networks as Endophenotypes of ADHD

This study is currently recruiting participants.
Verified September 2012 by National Taiwan University Hospital
Sponsor:
Information provided by (Responsible Party):
National Taiwan University Hospital
ClinicalTrials.gov Identifier:
NCT01682915
First received: September 7, 2012
Last updated: NA
Last verified: September 2012
History: No changes posted
  Purpose

Attention deficit/hyperactivity disorder (ADHD) is a common, impairing, clinically and genetically heterogeneous neuropsychiatric disorder with lifelong executive dysfunctions. The ultimate goal of this 3-year case-control imaging genomic study with unaffected siblings and typically developing (TD) children as controls is to identify useful imaging endophenotype for ADHD by investigating the structural connectivity, as assessed by diffusion spectrum imaging (DSI), and functional connectivity, as assessed by resting-state fMRI (rsfMRI) of brain regions related to cognitive/executive controls with regards to the ADHD status and the presence of dopamine transporter gene variants (DAT1).

Specific Aims:

  1. to validate the executive functions, visuospatial memory, and structural and functional connectivity in frontostriatal, and frontoparietal circuitries as effective neurocognitive endophenotypes;
  2. to correlate the data from structural and functional connectivity, neuropsychology, and ADHD core symptoms stratifying by the presence of ADHD, proband-unaffected sibling dyads, and the presence of DAT1 variant; and
  3. To investigate reported candidate genes, in addition to DAT1 variant, related to dopamine and noradrenergic neurotransmitter systems in the association with neurocognitive endophenotypes such as DRD1, DRD2, DRD4, DRD5, DBH, MAO-A, ADRA2A, ADRA2C, NET, and COMT.

Condition
Attention Deficit/Hyperactivity Disorder

Study Type: Observational
Official Title: Structural and Functional Connectivity of Frontostriatal and Frontoparietal Networks as Endophenotypes of Attention-deficit Hyperactivity Disorder

Resource links provided by NLM:


Further study details as provided by National Taiwan University Hospital:

Estimated Enrollment: 240
Study Start Date: August 2012
Estimated Study Completion Date: July 2015
Groups/Cohorts
Group 1: ADHD+DAT1, Probands
30 ADHD probands with DAT1 variants
Group 2: ADHD+DAT1, Unaffected sibling
30 same-sex unaffected siblings of Group 1
Group 3: ADHD Drug‐naïve, Probands
30 ADHD probands without DAT1 gene variants, who were age-, sex-, and IQ-matched to Group 1
Group 4: ADHD Drug‐naïve, unaffected sibling
30 same-sex unaffected siblings of Group 3
Matched controls
30 age-, sex- and IQ-matched TD controls for each of 4 groups

Detailed Description:

The sample (n=240, 8 groups, ages 10-20, IQ > 80) consists of (1) 30 ADHD probands with DAT1 variants, (2) 30 same-sex unaffected siblings, (3) 30 ADHD probands without DAT1 gene variants, who were age-, sex-, and IQ-matched to Group 1, (4) 30 same-sex unaffected siblings of Group 3, (5) 30 age-, sex- and IQ-matched TD controls for each of 4 groups (Groups 1, 2, 3 & 4).

The assessments include psychiatric interviews, self-administered questionnaires (CBCL and SNAP-IV for ADHD and behavioral problems; the SAICA for school and social function), neurocognitive assessments (WISC-III-R or WAIS-III for intelligence, Conner's CPT for sustained attention, inhibition, and vigilance, CANTAB for executive functions and visuo-spatial memory), and MRI assessments (Structural MRI, DSI and rsfMRI).

Brain Imaging: (1) Structural MRI (T1- and T2-weighted images), DSI and rsfMRI data will be acquired on a 3T MRI system with a 32-channel head coil. DSI employs a pulsed-gradient spin-echo echo planar imaging (EPI) sequence by applying 102 diffusion gradient vectors and the maximum diffusion sensitivity = 4000 s/mm2, and rsfMRI is a 6-minute scan using a gradient-echo EPI sequence with 180 volumes. (2) Structural connectivity analysis: DSI tractography will be performed using in-house software (DSI studio, http://dsi-studio.labsolver.org/Home). Tracts-of-interest in the frontostriatal circuit and the frontoparietal circuit will be identified, and tract-specific analysis will be used to analyze the microstructural integrity along individual tract bundles. (3) Functional connectivity analysis: SPM8 program and in-house MATLAB codes will be used for analyses of rsfMRI data. Region-of-interests (ROIs) will be placed in the nodes of the corresponding circuits according to an anatomical template (WFU_PickAtlas 3.03). These ROIs will serve for tract determination in the tractography procedure and for seed regions in which BOLD signals are extracted for regression analysis among nodes.

  Eligibility

Ages Eligible for Study:   12 Years to 20 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

The sample (n=240, 8 groups, ages 10-20, IQ > 80) consists of (1) 30 ADHD probands with DAT1 variants, (2) 30 same-sex unaffected siblings, (3) 30 ADHD probands without DAT1 gene variants, who were age-, sex-, and IQ-matched to Group 1, (4) 30 same-sex unaffected siblings of Group 3, (5) 30 age-, sex- and IQ-matched TD controls for each of 4 groups (Groups 1, 2, 3 & 4).

Criteria

Inclusion Criteria:

  • ADHD+DAT1 groups: Subjects aged 12‐20, who have clinical diagnosis of ADHD according to the DSM‐IV diagnostic criteria and who have risk alleles of DAT1 gene, regardless of having same‐sex unaffected siblings or the drug‐naïve status.
  • ADHD drug‐naïve groups: Subjects aged 12‐20, who have clinical diagnosis of ADHD according to the DSM‐IV diagnostic criteria, who do not have risk alleles of DAT1 gene, who have the same‐sex unaffected siblings and who have never been treated by medication for treating ADHD.

Exclusion Criteria:

  • These subjects will be excluded from the study if they have any of the following criteria: (1) Comorbidity with DSM‐IV‐TR diagnosis of pervasive developmental disorder, schizophrenia, schizoaffective disorder, delusional disorder, other psychotic disorder, organic psychosis, schizotypal personality disorder, bipolar disorder, depression, severe anxiety disorders or substance use; (2) With neurodegenerative disorder, epilepsy, involuntary movement disorder, congenital metabolic disorder, brain tumor, history of severe head trauma, and history of craniotomy; (3)With visual or hearing impairments, or motor disability which may influence the process of MRI assessment; and (4) Full‐scale IQ lower than 80. In addition, if the control subjects have ODD or CD, they will be excluded.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01682915

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

Locations
Taiwan
National Taiwan Univeristy Hospital Recruiting
Taipei, Taiwan
Contact: Susan Shur-Fen Gau, MD, PhD    886-2-23123456 ext 66802    gaushufe@ntu.edu.tw   
Sponsors and Collaborators
National Taiwan University Hospital
Investigators
Principal Investigator: Susan Shur-Fen Gau, MD, PhD National Taiwan University Hospital & College of Medicine
  More Information

No publications provided

Responsible Party: National Taiwan University Hospital, Susan Shur-Fen Gau
ClinicalTrials.gov Identifier: NCT01682915     History of Changes
Other Study ID Numbers: 201204071RIC
Study First Received: September 7, 2012
Last Updated: September 7, 2012
Health Authority: Taiwan: Department of Health

Keywords provided by National Taiwan University Hospital:
ADHD
endophenotype
executive function
diffusion spectrum imaging
resting-state fMRI
frontostriatal and frontoparietal circuitries
DAT1

Additional relevant MeSH terms:
Attention Deficit Disorder with Hyperactivity
Hyperkinesis
Attention Deficit and Disruptive Behavior Disorders
Mental Disorders Diagnosed in Childhood
Mental Disorders
Dyskinesias
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms

ClinicalTrials.gov processed this record on April 20, 2014