Peripheral Blood VA/TREM2 Levels and Their Correlation Analysis With the Development and Autistic Symptoms in Children With ASD (PBVTLCAASD)

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by social impairment, repetitive behaviors, and narrow interests. With advancements in diagnostic techniques, the prevalence of ASD has been increasing annually. However, due to its complex and diverse etiology, there is no definitive consensus on the pathogenic mechanism of ASD. Numerous studies indicate that genetics, environment, and other factors play crucial roles in the onset of ASD.

Vitamin A (VA) exerts its effects in the body through its active metabolite, retinoic acid (RA), which regulates the transcriptional activity and expression of downstream genes by binding to retinoic acid receptors (RARs/RXRs). Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) is an immunoglobulin-like receptor present on microglial cells, with functions including inhibiting the production of inflammatory factors and engulfing apoptotic neurons. Recent foreign studies show a significant decrease in TREM2 levels in the brain tissue of ASD patients. However, there is limited research on the relationship between TREM2 and ASD.

In our previous animal experiments, we observed a reduction in TREM2 in the prefrontal cortex of the brain in ASD model rats. Administering overexpressed TREM2 improved autism-like behavior in ASD model rats, and supplementing RA upregulated the expression of RA-RARα and TREM2, modulated microglial cell activation, and improved autism-like behavior in rats. Therefore, we believe that the RA/RARα pathway regulates the TREM-2 signaling pathway, mediating changes in microglial cells, and TREM2 may be involved in the pathogenesis of ASD.

Soluble TREM2 (sTREM2) is formed by the extracellular domain shedding of TREM2 under the action of ADAM protease. Research indicates that the expression of sTREM2 can be detected in cerebrospinal fluid and plasma. However, the connection between VA, sTREM2 levels, and the behavioral and developmental levels of children with ASD remains unclear and requires further clinical research to validate. This will help deepen our understanding of TREM2 expression in ASD, its potential biological functions, and the role of RA.

Study Overview

• Status: Recruiting
• Conditions: ASD
• Intervention / Treatment: Diagnostic test: DSM-5

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: wei Hua; Phone Number: 18580476890; Email: weihua6280@163.com

Study Locations

• China
  • Chongqing
    • Chongqing, Chongqing, China, 400000
      • Recruiting
      • Chongqing Medical University Affiliated Children's Hospital
      • Contact: wei Hua; Phone Number: 18580476890; Email: weihua6280@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

The Children's Health Department (Health Management Department) of Chongqing Medical University Affiliated Children's Hospital is recruiting 50 children with ASD and 50 typical children, aged between 3 and 8 years old. ASD diagnosis must comply with the DSM-5 diagnostic criteria.

Description

Inclusion Criteria:

• The Children's Health Department (Health Management Department) of Chongqing Medical University Affiliated Children's Hospital is recruiting 50 typical children and 50 children with ASD. Disease diagnosis will be conducted by professional doctors, and ASD diagnosis must comply with the DSM-5 diagnostic criteria.

Exclusion Criteria:

• Patients or their family members unable to cooperate with blood collection for testing are excluded. Exclusion criteria also involve a history of other neurological disorders, chromosomal diseases, genetic metabolic disorders, and other significant physical illnesses such as auditory or visual impairments, epilepsy, phenylketonuria, tuberous sclerosis, neurofibromatosis, severe head trauma, autoimmune diseases, and disorders related to the endocrine, cardiovascular, pulmonary, hepatic, or renal systems. Patients' legal guardians refusing to participate in the project are also excluded.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Experimental Group; Children with ASD	Diagnostic test: DSM-5; Using DSM-5 for diagnostic testing of the children in the study group.
Control Group; Normal Children	Diagnostic test: DSM-5; Using DSM-5 for diagnostic testing of the children in the study group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood VA/sTREM2 level	Using an ELISA assay kit to detect the serum sTREM2 levels and employing high-performance liquid chromatography (HPLC) to measure the Vitamin A content in peripheral blood.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Autistic Symptoms	Using the ADOS (Autism Diagnostic Observation Schedule) scale to analyze the severity of autism symptoms in autistic children.	1 week

Collaborators and Investigators

• Sponsor: Hua Wei

Study record dates

Study Major Dates

• Study Start (Actual): November 20, 2023
• Primary Completion (Estimated): March 31, 2024
• Study Completion (Estimated): October 31, 2024

Study Registration Dates

• First Submitted: December 18, 2023
• First Submitted That Met QC Criteria: December 18, 2023
• First Posted (Estimated): January 3, 2024

Study Record Updates

• Last Update Posted (Estimated): January 3, 2024
• Last Update Submitted That Met QC Criteria: December 18, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Autism Spectrum Disorder; Autistic Disorder
• Other Study ID Numbers: (2023) Lund Review No.452

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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