Neurotransmitter Levels in Children With Specific Learning Disorder (SLD)

Biochemical and Docking Evidence of Neurotransmitter Dysregulation in Specific Learning Disorder

The aim of this clinical trial was to measure how specific neurotransmitter levels in children with Specific Learning Disorder (SLD) change compared to controls. The relationship between these markers and the measured markers will be determined both theoretically and experimentally using various neuropsychological tests. The fundamental questions it aims to answer are

Did neurotransmitter levels increase or decrease in the patient group? Are the neurotransmitter levels measured in the neuropsychological tests related? Can the measured neurotransmitters be used to predict the disease?

Participants:

A single visit to the clinic, a blood sample, and neuropsychological tests will be administered on the same day.

Study Overview

• Status: Completed
• Conditions: Specific Learning Disability; Healthy (Controls)
• Intervention / Treatment: Procedure: Blood Product; Other: Elisa test

Detailed Description

The purpose of this investigation was to assess the levels in serum of key neurotransmitters and their precursors (glutamate, L-arginine, and nitric oxide) in children with SLD and also to integrate these biochemical results with molecular docking analyses of their interactions with phospholipase A2 (PLA2) and N-methyl D-aspartate receptors (NMDA), both of which play significant roles in learning function in these patients.

The research group consisted of 20 children aged 7-14 years who had been diagnosed with SLD using DSM-5 criteria, as well as 20 age-matched, gender-matched, and educationally matched healthy controls. The children in the study group underwent the Stroop Test [Total Error Scores, Total Time Scores, Total Correction] and the Wechsler Intelligence Scale for Children (WISC-IV) subtests, and the results were scored. The serum concentrations of glutamate, L-arginine, and nitric oxide (NO) were determined using ELISA. The diagnostic ability of the biomarkers was evaluated using ROC analysis. Additionally, the interactions of glutamate and L-arginine with the PLA2 enzyme and the NMDA receptor were examined using molecular docking analysis.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Turkey (Türkiye)
  • Central
    • Sivas, Central, Turkey (Türkiye), 58146
      • Sivas Cumhuriyet University

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Study group: no additional mental disorder except a specific learning disability,
• The control group had no mental illness.
• Having no head injury or neurological illness for all groups.
• There is no drug that might possibly alter cognitive functions for all populations.

Exclusion Criteria:

• The study group had a mental disease other than a specific learning disability and ADHD.
• The control group had any mental condition.
• Having a head injury or neurological illness in all categories.
• Using drugs that may impair cognitive functioning in all groups those with additional diseases

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Collection of blood samples; A 5 ml blood sample will be taken from the left arterial vein of the individuals in the study group, and serum will be obtained from it. The neurotransmitter concentrations specified in the serum samples will be measured with an ELISA test kit.	Procedure: Blood Product; Collecting 5 ml blood samples from the left atrial vein, after that obtaining serum from it.; Other: Elisa test; Measurement of glutamate, nitric oxide, and L-arginine concentrations in the blood samples obtained using an ELISA test kit.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mesurment of serum neurotransmitters levels	Serum Glutamate Levels (measured in µmol/L by ELISA at baseline) Serum L-Arginine Levels (measured in µmol/L by ELISA at baseline) Serum Nitric Oxide (NO) Levels (measured in µmol/L by ELISA at baseline)	6 months
Verbal Comprehension Index (VCI)	Change in Verbal Comprehension Index (VCI) score from baseline to 6 months.Points on a scale (range: 40-160; higher scores indicate better performance)	6 month
Perceptual Reasoning Index (PRI)	Change in Perceptual Reasoning Index (PRI) score from baseline to 6 months. Change in Perceptual Reasoning Index (PRI) score from baseline to 6 months.	6 months
Working Memory Index (WMI)	Change in Working Memory Index (WMI) score from baseline to 6 months. Points on a scale (range: 40-160; higher scores indicate better performance)	6 months
Processing Speed Index (PSI)	Change in Processing Speed Index (PSI) score from baseline to 6 months. Points on a scale (range: 40-160; higher scores indicate better performance).	6 months
Stroop Test Performance	Change in Stroop Test total errors, total time, and total corrections from baseline to 6 months.Seconds (for time) and number of errors/corrections; lower scores indicate better performance.	6 months
Full Scale IQ (FSIQ)	Change in Full Scale IQ (FSIQ) score from baseline to 6 months.oints on a scale (range: 40-160; higher scores indicate better performance)	6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Molecular docking analysis	Binding affinity values (in kcal/mol) of Glutamate and L-Arginine ligands to NMDA receptor and PLA2 enzyme active sites will be evaluated using molecular docking analysis. Lower binding affinity (more negative kcal/mol) indicates stronger interaction.Lower (more negative) binding energy indicates a stronger binding affinity.	6 months
ROC analysis performance of biomarkers	Receiver Operating Characteristic (ROC) analysis will be performed to determine the diagnostic performance of selected biomarkers. Parameters include Area Under the Curve (AUC), sensitivity, specificity, cut-off value, and Youden Index. AUC value (range 0-1); higher values indicate better diagnostic performance.	6 months

Collaborators and Investigators

• Sponsor: Dilara Ulger Ozbek
• Investigators: Study Director: Dilara ULGER OZBEK, Dr., Cumhuriyet University

Study record dates

Study Major Dates

• Study Start (Actual): October 22, 2019
• Primary Completion (Actual): October 21, 2020
• Study Completion (Actual): April 16, 2021

Study Registration Dates

• First Submitted: September 30, 2025
• First Submitted That Met QC Criteria: November 19, 2025
• First Posted (Actual): November 20, 2025

Study Record Updates

• Last Update Posted (Actual): November 20, 2025
• Last Update Submitted That Met QC Criteria: November 19, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Glutamate; L-arginine; nitric oxide; Specific learning Disorder; molecualr docking
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Mental Disorders; Neurobehavioral Manifestations; Neurodevelopmental Disorders; Communication Disorders; Learning Disabilities; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Specific Learning Disorder
• Other Study ID Numbers: SCÜ Child Psychiatry

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