Multimodal Neurobiological Approaches to Explore the Gene-Environment Interactions in ADHD

A Study With Multimodal Neurobiological Approaches to Explore the Interactions Between Monoamine Transporter Genes and Environmental Factors on Attention Deficit Hyperactivity Disorder.

Previous studies have demonstrated significant associations of attention-deficit hyperactivity disorder (ADHD) with monoamine transporter genes, including dopamine transporter gene (DAT1), norepinephrine transporter gene (SLC6A2), and serotonin transporter gene (SLC6A4) as well as the important role of environmental factors in the pathogenesis of ADHD. Hence, investigating how genes and environments interact with each other may contribute to the understanding of the pathophysiological mechanisms of ADHD. In this 3-year project, investigators will explore the complex gene-environment interplay in ADHD with multimodal neurobiological approaches, including neuropsychology, neuroimaging, and metabolites, in order to identify the crucial pathophysiological pathways from genes to the brain.

Study Overview

• Status: Completed
• Conditions: Monoamine Transporter Genes; Environmental Factors

Detailed Description

In the present project, investigators aim to explore the complex gene-environment interplay in children with ADHD to identify the crucial pathophysiological pathways from genes to the brain. To achieve our objective, investigators will use multimodal neurobiological approaches to effectively resolve the four major challenges in exploring gene-environment interactions on ADHD.

1. investigators will use multiple levels of neurobiological approaches to identify the interactions between monoamine transporter genes and environment on ADHD, including neuropsychology, neuroimaging, and neuroactive metabolites in plasma, which will provide larger effects than clinical diagnosis.
2. investigators will employ correlation analyses to test for the presence of correlations between the monoamine transporter genotypes and the environmental factors.
3. investigators will use both categorical (diagnosis of ADHD) and dimensional (inattention and hyperactivity-impulsivity symptoms of ADHD) approaches to assess the interaction effects between monoamine transporter genes and environment.
4. investigators will conduct interactions with ageitems to model more accurately the effects of age, which may be non-linearly related to the neurobiological basis of ADHD.

• Study Type: Observational
• Enrollment (Actual): 202

Contacts and Locations

• Study Contact: Name: Chi-Yung Shang, MD, PhD; Phone Number: 66965 +886-2-23123456; Email: cyshang@ntu.edu.tw

Study Locations

• Taiwan
  • Taipei, Taiwan, 110
    • National Taiwan University Hospital
  • Taipei, Taiwan
    • college of Medicine, National Taiwan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years to 16 years (Child)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

120 drug-naïve patients with ADHD, aged 7-16, and 120 age- and sex-matched typically developing controls will be recruited in this project.

Description

Inclusion Criteria:

• Children or adolescents, between 7 and 16 years of age, must have clinical diagnosis of ADHD according to the DSM-5 diagnostic criteria.
• They have to be medication-naïve. They never receive any medication for the treatment of ADHD.
• They and their parents must understand sufficiently to communicate properly with the investigators.
• They must have a Full-Scale Intelligence Quotient(FIQ) score greater than 80.

Exclusion Criteria:

• They have a major psychiatric comorbid disorder, including schizophrenia, schizoaffective disorder, affective disorders, or autism spectrum disorder.
• They have a past history of seizure, or they are taking antiepileptic drugs.
• They have a past history of substance dependence or abuse, including nicotine, alcohol, amphetamine, or any over-the-counter medication.
• They have a past history of major systemic disease.
• They are using Chinese herbs or health supplements.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
ADHD GROUP; Subjects with clinical diagnosis of ADHD according to the DSM-V criteria
TD GROUP; Typically development controls without lifetime diagnosis with ADHD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ADHD symptoms	Subjects will be interviewed by Chinese Version of the Kiddie Epidemiologic version of the Schedule for Affective Disorders and Schizophrenia (K-SADS-E)	1 hour

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neuropsychological testing	Subjects will be assessed by the Cambridge Neuropsychological Test Automated Battery (CANTAB)	1.5 hours
Neuropsychological testing	Subjects will be assessed by the Continuous Performance Test	15 mins
Metabolomics profiling	All the biomarkers are relative ratios. Although all the names of metabolites examined in this study cannot be listed due to the upper limitation of word number (999 characters), the metabolomics profiling includes Hydroxybutyric acid, Undecanedicarboxylic acid, Methyladenosine, Hydroxybutyric acid, Furoylglycine, Hydroxy, Hydroxybutyric acid, Hydroxycaproic acid,Oxoglutarate, Hydroxyisovaleric acid, Hydroxymethylglutaric acid,Indolepropionic acid, Methyladenine, Methylhistidine, Methylindole, Methylxanthine, Pyridylacetic acid, Guanidinobutanoic acid, Dihydrothymine, Aminolevulinic acid, Dodecenoic acid, Hydroxylysine P66-59, Methylcytidine, Acetoacetic acid, Acrylamide, Allose, AMP, Androstenedione, Aspartic acid, Betaine, Bradykinin, Carnitine, Cholic Acid, cis-Aconitate, cis-Fenpropimorph, citric acid, Corticosterone, Creatine, Creatinine, D-Arginine, Decanoylcarnitine, Dehydroascorbic acid, Deoxycholic acid, Deoxyribose, etc.	10 mins
Brain imaging	Subjects will be assessed by structural and functional brain imaging, including xoxel-based morphometry, diffusion spectrum imaging, resting-state fMRI, and counting Stroop task fMRI	1 hour

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Investigators: Study Director: Susan Shur-Fen Gau, MD, PhD, Department of Psychiatry, National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 19, 2020
• Primary Completion (Actual): July 5, 2023
• Study Completion (Actual): July 5, 2023

Study Registration Dates

• First Submitted: August 27, 2020
• First Submitted That Met QC Criteria: September 28, 2020
• First Posted (Actual): September 30, 2020

Study Record Updates

• Last Update Posted (Actual): March 19, 2024
• Last Update Submitted That Met QC Criteria: March 17, 2024
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: 201912085RINA

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No