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

NCT01682915 | Completed DMC

• 1 other identifier: 201204071RIC
• Study Type: observational
• Target: 240
• Locations: 1 country
• Sites: 1

Brief Summary

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. 1.to validate the executive functions, visuospatial memory, and structural and functional connectivity in frontostriatal, and frontoparietal circuitries as effective neurocognitive endophenotypes;
2. 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. 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.

Conditions

Attention Deficit/Hyperactivity Disorder

Keywords

ADHD; endophenotype; executive function; diffusion spectrum imaging; resting-state fMRI; frontostriatal and frontoparietal circuitries; DAT1

Study Arms (5)

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

Eligibility Criteria

• Age: 12 Years - 20 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• 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).

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Taiwan University Hospital: lead

Study Sites (1)

National Taiwan Univeristy Hospital

Taipei, Taiwan

Location

Related Publications (2)

• Lin HY, Kessler D, Tseng WI, Gau SS. Increased Functional Segregation Related to the Salience Network in Unaffected Siblings of Youths With Attention-Deficit/Hyperactivity Disorder. J Am Acad Child Adolesc Psychiatry. 2021 Jan;60(1):152-165. doi: 10.1016/j.jaac.2019.11.012. Epub 2019 Nov 26.

  PMID: 31778781 DERIVED

• Chiang HL, Hsu YC, Shang CY, Tseng WI, Gau SS. White matter endophenotype candidates for ADHD: a diffusion imaging tractography study with sibling design. Psychol Med. 2020 May;50(7):1203-1213. doi: 10.1017/S0033291719001120. Epub 2019 May 22.

  PMID: 31115278 DERIVED

MeSH Terms

Conditions

Attention Deficit Disorder with Hyperactivity

Condition Hierarchy (Ancestors)

Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Mental Disorders

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Susan Shur-Fen Gau

Study Record Dates

• First Submitted: September 7, 2012
• First Posted: September 11, 2012
• Study Start: August 1, 2012
• Primary Completion: July 31, 2015
• Study Completion: July 31, 2015
• Last Updated: September 2, 2021

Record last verified: 2021-09

Locations

TW (1)