Gut Microbiome and Serum Metabolome Alterations in ADHD Patients (ADHD)

Gut Microbiome and Serum Metabolome Alterations in Attention-deficit/Hyperactivity Disorder Patients

Host-microbe interactions play a key role in brain development and function and in the etiology of neurodevelopmental disorders. Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous disorder that affects 1 in 20 children and results in poor life-time outcomes. However, the etiology of ADHD is unclear and its diagnosis and treatment are still challenging. Different factors reported to be associated with the risk of developing ADHD and/or linked to different ADHD manifestations have also been linked to shifts in gut microbiota composition, suggesting a link between the microbiota and the disorder. Here, we will perform a metagenome-wide association study and serum metabolomics profiling in a cohort of control and ADHD, 6-15 years, Chinese individuals. We aim to identify ADHD-associated gut microbial species linked to changes in circulating metabolites. We also aim to find the possible intervention strategy in ADHD by targeting the gut microbiota.

Study Overview

• Status: Completed
• Conditions: Attention-deficit/Hyperactivity Disorder

• Study Type: Observational
• Enrollment (Actual): 207

Contacts and Locations

Study Locations

• China
  • Shaanxi
    • Xi'an, Shaanxi, China, 710032
      • Department of Pediatrics, Xijing Hospital, the Fourth Military Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 15 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

All subjects were drug-naive at the time of recruitment, and the ADHD tests were administered before the subjects were given any medication. The subjects will be recruited from Xijing Hospital and elementary and secondary schools in China.

Description

Inclusion Criteria:

Diagnoses of the children with ADHD were made in Xijing Hospital according to criteria described in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). Children with ADHD had an IQ score above 70.

Exclusion Criteria:

Children who had a past history of or were currently affected by neurological diseases, including convulsive disorders or brain damage; or who had any evidence of comorbid psychiatric conditions, such as Tourette's syndrome, IQ below 70, pervasive developmental disorder (autism), bipolar disorder, psychosis, language difficulties or learning disorders (reading disorders, mathematics disorders and disorders of written expression).

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
ADHD-patients; The children and adolescent 6-15 years old with ADHD. Diagnoses of the children with ADHD were made in Xijing Hospital according to criteria described in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). Children with ADHD had an IQ score above 70.
Controls-healthy children; Age- and gender- matched healthy 6-15 years old children and adolescent.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ADHD-associated gut microbial species alterations	Gut metagenome analysis with fecal samples	2018-2020

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ADHD-associated circulating metabolites alterations	Circulation metabonomics analysis with serum samples	2018-2020

Collaborators and Investigators

• Sponsor: Xijing Hospital
• Investigators: Principal Investigator: Lize Xiong, M.D./Ph.D., Professor and President, Xijing Hospital

Publications and helpful links

General Publications

• Sharma A, Couture J. A review of the pathophysiology, etiology, and treatment of attention-deficit hyperactivity disorder (ADHD). Ann Pharmacother. 2014 Feb;48(2):209-25. doi: 10.1177/1060028013510699. Epub 2013 Nov 1.
• Aarts E, Ederveen THA, Naaijen J, Zwiers MP, Boekhorst J, Timmerman HM, Smeekens SP, Netea MG, Buitelaar JK, Franke B, van Hijum SAFT, Arias Vasquez A. Gut microbiome in ADHD and its relation to neural reward anticipation. PLoS One. 2017 Sep 1;12(9):e0183509. doi: 10.1371/journal.pone.0183509. eCollection 2017.
• Evangelisti M, De Rossi P, Rabasco J, Donfrancesco R, Lionetto L, Capi M, Sani G, Simmaco M, Nicoletti F, Villa MP. Changes in serum levels of kynurenine metabolites in paediatric patients affected by ADHD. Eur Child Adolesc Psychiatry. 2017 Dec;26(12):1433-1441. doi: 10.1007/s00787-017-1002-2. Epub 2017 May 19.

Helpful Links

• Wikipedia

Study record dates

Study Major Dates

• Study Start (Actual): March 20, 2018
• Primary Completion (Actual): February 27, 2020
• Study Completion (Actual): May 27, 2020

Study Registration Dates

• First Submitted: February 21, 2018
• First Submitted That Met QC Criteria: February 21, 2018
• First Posted (Actual): February 27, 2018

Study Record Updates

• Last Update Posted (Actual): August 27, 2021
• Last Update Submitted That Met QC Criteria: August 23, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Attention-deficit/hyperactivity disorder; metagenome; circulating metabolites
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Dyskinesias; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Attention Deficit Disorder with Hyperactivity; Hyperkinesis
• Other Study ID Numbers: KY20182002-1

Drug and device information, study documents

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