Biomarkers of ASD/ADHD and Factors Affecting Anxiety and Depression in Children and Young Adults

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

• Ages 6 months to 25 years
• All sexes
• Healthy volunteers accepted
• Child, Adult

Study population: The study will recruit approximately 800 participants from early infancy to young adulthood across 10 international sites. OS1 will include infants at increased neurodevelopmental risk: very or extremely preterm infants (<32 or <28 weeks), term-born infants with perinatal asphyxia or hypoxic-ischaemic encephalopathy, and a comparison group of term-born infants without risk factors. Infants are enrolled within the first 12 months and followed to 42 months. OS2 will include children (5-10 years), adolescents (11-18 years), and young adults (19-25 years) with confirmed diagnoses of ASD, ADHD, or DCD, conditions linked to elevated anxiety and depression risk. Recruitment aims for balanced sex representation and diverse socioeconomic and cultural backgrounds.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

About this study

Official title: Biomarker Discovery for Predicting Autism Spectrum Disorder and Attention/Hyperactivity Disorders, and Identification of Environmental Factors Influencing Anxiety and Depression in Children, Adolescents, and Young Adults

Conditions

ADHD - Attention Deficit Disorder With Hyperactivity, Autism Spectrum Disorder (ASD), Developmental Coordination Disorder (DCD)

Keywords

Attention Deficit Disorder with Hyperactivity, Autism spectrum disorder, Developmental Coordination Disorder

Medical subject headings

Attention Deficit Disorder with Hyperactivity, Autism Spectrum Disorder, Motor Skills Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

What is being measured

The primary outcome is the main question the study is designed to answer.

1. EEG-Based Effective Brain Connectivity Network (EBCN) Features for ASD/ADHD Prediction - OS1

   Quantitative features extracted from single-layer and multi-layer effective brain connectivity networks using electroencephalography (EEG). These features characterize directional, causal interactions between brain regions using Granger Causality and Dynamic Causal Modelling, generating dimensionless connectivity indices (ranging 0-1) to identify early neurophysiological markers predictive of Autism Spectrum Disorder (ASD) and/or Attention-Deficit/Hyperactivity Disorder (ADHD) diagnosis at 42 months of age.

   Measured: Baseline (6 months corrected age), 12 months, 18 months, and 24 months

2. Effective Brain Connectivity Networks (EBCN) Features for ASD/ADHD Prediction - OS1

   Composite score derived from quantitative graph-theoretical features extracted from multilayer effective brain connectivity networks constructed using simultaneous electroencephalography (EEG, 32-channel) and functional near-infrared spectroscopy (fNIRS, 24-channel). Features quantify directional causal interactions between brain regions using Granger Causality and/or Dynamic Causal Modelling methods. Machine learning algorithms will integrate multiple EBCN features to generate a single predictive probability score (range 0-1, where higher values indicate greater likelihood of ASD/ADHD diagnosis) indicating likelihood of Autism Spectrum Disorder (ASD) and/or Attention-Deficit/Hyperactivity Disorder (ADHD) diagnosis at 42 months of age.

   Measured: Baseline (6 months corrected age), 12 months, 18 months, and 24 months

3. Clinical Diagnosis of ASD and/or ADHD - OS1

   Clinical diagnosis of Autism Spectrum Disorder (ASD) and/or Attention-Deficit/Hyperactivity Disorder (ADHD) established using ICD-11 and DSM-5-TR diagnostic criteria administered by qualified clinicians.

   Measured: 42 months (corrected age)

4. DNA Methylation Profiles from Buccal Swabs - OS1 and OS2

   Epigenetic DNA methylation profiles analyzed from buccal swab samples using standard microarray technique. Methylation levels are measured as beta values representing the proportion of methylated cytosines at specific CpG sites.

   Measured: Baseline (6 months corrected age), 12 months, 18 months, and 24 months for OS1. Baseline, 3 months, 6 months and 9 months for OS2

5. Metabolomic Signatures from Stool and Urine - OS1 and OS2

   Metabolomic analysis of stool and urine samples using nuclear magnetic resonance spectroscopy and mass spectrometry to identify metabolite concentrations and profiles relevant to neurodevelopmental outcomes.

   Measured: Baseline (6 months corrected age), 12 months, 18 months, and 24 months for OS1. Baseline, 3 months, 6 months and 9 months for OS2

6. Shotgun Metagenomic Microbiome Profiles from Stool - OS1 and OS2

   Comprehensive shotgun metagenomics analysis of stool samples characterizing the composition and potential function of bacteria, archaea, fungi, and viruses. Measured as relative abundance (percentage), taxonomic diversity, and alpha/beta diversity indices.

   Measured: Baseline (6 months corrected age), 12 months, 18 months, and 24 months for OS1. Baseline, 3 months, 6 months and 9 months for OS2

7. General Cognitive Development - OS1

   Assessment of general cognitive development using the Wechsler Preschool and Primary Scale of Intelligence | Fourth Edition (WPPSI-IV) at 42 months and the Bayley Scales of Infant and Toddler Development, Fourth Edition (Bayley-4) at 12 and 24 months. The WPPSI-IV provides a Full Scale IQ with scores ranging from 40 to 160 (mean=100, SD=15), where higher scores indicate better cognitive abilities. The Bayley-4 provides composite scores ranging from 40 to 160 (mean=100, SD=15) for cognitive, language, and motor domains, with higher scores indicating better developmental functioning.

   Measured: Baseline (6 months corrected age), 12 months, 18 months, 24 months, and 42 months

8. Attention Function - OS1

   Assessment of attention function using age-appropriate subtests from the Bayley Scales of Infant and Toddler Development, Fourth Edition (Bayley-4) for ages 6-24 months and the Wechsler Preschool and Primary Scale of Intelligence | Fourth Edition (WPPSI-IV) attention/executive function subtests at 42 months. Scaled scores range from 1 to 19 (mean=10, SD=3), with higher scores indicating better attention function.

   Measured: Baseline (6 months corrected age), 12 months, 18 months, 24 months, and 42 months

9. Temperament Assessment - OS1

   Assessment of infant temperament using the Infant Behavior Questionnaire-Revised, Short Version (IBQ-R Short) at 12 months, the Early Childhood Behavior Questionnaire (ECBQ) at 24 months, and the Child Behavior Questionnaire (CBQ) at 42 months, all completed by parents/caregivers. Scores are averaged across items for each temperament dimension, ranging from 1 to 7, with higher scores indicating greater intensity of the specific temperament characteristic being measured.

   Measured: Baseline (6 months corrected age), 12 months, 18 months, 24 months, and 42 months

10. Anxiety Symptoms - OS1

    Assessment of anxiety symptoms using the Infant-Toddler Social \& Emotional Assessment-Revised (ITSEA) at 12 and 24 months and the Child Behavior Checklist 1.5-5 (CBCL 1.5-5) at 42 months, completed by parents/caregivers. The ITSEA anxiety domain provides T-scores (mean=50, SD=10), and the CBCL provides T-scores for the anxiety problems subscale (mean=50, SD=10), with higher scores indicating greater anxiety symptoms.

    Measured: Baseline (6 months corrected age), 12 months, 18 months, 24 months, and 42 months

11. Executive Functions - OS1

    Assessment of executive functions using age-appropriate measures including the Bayley Scales of Infant and Toddler Development, Fourth Edition (Bayley-4) cognitive subtests at 6-24 months and the Wechsler Preschool and Primary Scale of Intelligence | Fourth Edition (WPPSI-IV) executive function subtests at 42 months. Scaled scores range from 1 to 19 (mean=10, SD=3), with higher scores indicating better executive functioning.

    Measured: Baseline (6 months corrected age), 12 months, 18 months, 24 months, and 42 months

12. Social-Communication Skills - OS1

    Assessment of social-communication abilities using the Ages and Stages Questionnaire-3 (ASQ-3) communication and personal-social domains, the Infant-Toddler Social \& Emotional Assessment-Revised (ITSEA) social competence domains at 12 and 24 months, and the Child Behavior Checklist 1.5-5 (CBCL 1.5-5) social problems subscale at 42 months. ASQ-3 domain scores indicate whether development is on schedule, requires monitoring, or indicates concern. ITSEA and CBCL provide T-scores (mean=50, SD=10), with higher scores on competence domains indicating better social skills and higher scores on problem scales indicating greater difficulties.

    Measured: Baseline (6 months corrected age), 12 months, 18 months, 24 months, and 42 months

13. Autism Traits - OS1

    Assessment of autism traits using the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2) Toddler Module at 12, 18, and 24 months and Module 1-3 at 42 months, administered by trained researchers. Comparison scores range from 1 to 10, with scores of 1-2 indicating minimal-to-no concern, 3-4 indicating mild concern, 5-7 indicating moderate concern, and 8-10 indicating high likelihood of autism spectrum disorder.

    Measured: Baseline (6 months corrected age), 12 months, 18 months, 24 months, and 42 months

14. Quality of Life - OS1

    Assessment of infant/child quality of life using the Pediatric Quality of Life Inventory (PedsQL) parent proxy-report version, completed by parents/caregivers. Total scores range from 0 to 100, with higher scores indicating better health-related quality of life.

    Measured: Baseline (6 months corrected age), 12 months, 18 months, 24 months, and 42 months

15. Dietary Intake - Methyl Donor Nutrients - OS1

    Assessment of dietary intake of methyl-donor nutrients (folate, vitamin B12, choline, betaine, and methionine) relevant to DNA methylation analyses using validated Food Frequency and Food Preference Questionnaires completed by parents/caregivers. At 6 and 12 months, feeding mode (exclusively breast-fed, formula-fed, or mixed feeding) is recorded. Nutrient intake is reported in micrograms or milligrams per day depending on the nutrient, with values compared to age-appropriate dietary reference intakes.

    Measured: Baseline (6 months corrected age), 12 months, 18 months, 24 months, and 42 months

16. Personal Natural Environment (PNE) Factors Causally Associated with Anxiety and Depression - OS2

    Identification and quantification of personal natural environmental factors (e.g., sleep patterns, physical activity, social interactions, screen time) causally associated with age-specific anxiety and depression symptom severity and developmental progression, measured through repeated assessments of validated mental health questionnaires combined with ecological momentary assessment data. Analysis uses the PNE-GGB-MH (Personal Natural Environment-Granger-causality Graph-Based Mental Health) computational model to establish directional causal relationships. Results report the strength of causal associations (standardized coefficients ranging from -1 to +1), with higher absolute values indicating stronger causal effects, and positive/negative signs indicating the direction of effect on mental health outcomes.

    Measured: Through study completion, up to 36 weeks

17. Depression Symptoms (Ages 5-10) - OS2

    Assessment of depressive symptoms using the Children's Depression Inventory (CDI), a validated self-report questionnaire. Total scores range from 0 to 54, with higher scores indicating greater depressive symptoms.

    Measured: Baseline, 3 months, 6 months and 9 months.

18. Depression Symptoms (Ages 11-18) - OS2

    Assessment of depressive symptoms using the Children's Depression Inventory (CDI; total score range 0-54) or Beck Depression Inventory-II (BDI-II; total score range 0-63) depending on age and clinical appropriateness. For both scales, higher scores indicate greater depressive symptoms.

    Measured: Baseline, 3 months, 6 months and 9 months.

19. Depression Symptoms (Ages 19-25) - OS2

    Assessment of depressive symptoms using the Beck Depression Inventory-II (BDI-II), a validated self-report questionnaire. Total scores range from 0 to 63, with higher scores indicating greater depressive symptoms.

    Measured: Baseline, 3 months, 6 months and 9 months.

20. Autism Spectrum Disorder Traits (Ages 5-10) - OS2

    Assessment of autism traits using the Childhood Autism Rating Scale (CARS), completed by parents/caregivers. Total scores range from 15 to 60, with higher scores indicating greater severity of autism-related behaviors.

    Measured: Baseline only

21. Autism Spectrum Disorder Traits (Ages 11-25) - OS2

    Assessment of autism traits using the Autism Spectrum Quotient-10 (AQ-10), a brief screening questionnaire. Total scores range from 0 to 10, with higher scores indicating greater likelihood of autism spectrum traits.

    Measured: Baseline only

22. ADHD Symptoms (Ages 5-18) - OS2

    Assessment of ADHD symptoms using the Adult ADHD Self-Report Scale Version 1.1 (ASRS v1.1). Part A scores range from 0 to 24, with higher scores indicating greater ADHD symptom severity.

    Measured: Baseline, 3 months, 6 months and 9 months.

23. Quality of Life (Ages 5-10) - OS2

    Assessment of health-related quality of life using KIDSCREEN-27 Proxy version completed by parents/caregivers. Scores are transformed to T-values (mean=50, SD=10) for five dimensions, with higher scores indicating better health-related quality of life.

    Measured: Baseline, 3 months, 6 months and 9 months.

24. Quality of Life (Ages 11-18) - OS2

    Assessment of health-related quality of life using KIDSCREEN-27 self-report version. Scores are transformed to T-values (mean=50, SD=10) for five dimensions, with higher scores indicating better health-related quality of life.

    Measured: Baseline, 3 months, 6 months and 9 months.

25. Quality of Life (Ages 19-25) - OS2

    Assessment of health-related quality of life using the Short Form-36 (SF-36) questionnaire. Scores range from 0 to 100 for each of eight domains, with higher scores indicating better health-related quality of life.

    Measured: Baseline, 3 months, 6 months and 9 months.

26. Anxiety Symptoms (Ages 5-18) - OS2

    Assessment of anxiety symptoms using the Spence Children's Anxiety Scale (SCAS; total score range 0-114) or Beck Anxiety Inventory (BAI; total score range 0-63) depending on age. For both scales, higher scores indicate greater anxiety symptoms.

    Measured: Baseline, 3 months, 6 months and 9 months.

27. Anxiety Symptoms (Ages 19-25) - OS2

    Assessment of anxiety symptoms using the Generalized Anxiety Disorder-7 (GAD-7) questionnaire. Total scores range from 0 to 21, with higher scores indicating greater anxiety symptom severity.

    Measured: Baseline, 3 months, 6 months and 9 months.

28. Physical Activity Level (Ages 5-18) - OS2

    Assessment of physical activity using the Physical Activity Questionnaire for Children (PAQ-C; for ages below 14) or Physical Activity Questionnaire for Adolescents (PAQ-A; for ages 14-18) as age-appropriate. Scores range from 1 to 5, with higher scores indicating higher levels of physical activity.

    Measured: Baseline, 3 months, 6 months and 9 months.

29. Physical Activity Level (Ages 19-25) - OS2

    Assessment of physical activity using the International Physical Activity Questionnaire Short Form (IPAQ-SF). Results are reported as metabolic equivalent of task minutes per week (MET-min/week), with higher values indicating greater physical activity levels.

    Measured: Baseline, 3 months, 6 months and 9 months.

30. Objective Physical Activity Measurement - OS2

    Objective measurement of physical activity using Axivity AX-3 wearable accelerometer worn for 7 consecutive days. Data recorded as 3-axis acceleration for activity recognition analysis.

    Measured: Between baseline and visit 1 (approximately 2 weeks); then at 12-week intervals through study completion

31. Dietary Intake - Methyl Donor Nutrients - OS2

    Assessment of dietary intake using validated Food Frequency and Food Preference Questionnaires to capture information on methyl-donor nutrient intake relevant to DNA methylation analyses.

    Measured: Food frequency every 2 weeks and food preference at baseline only

32. Sleep pattern - Adolescent Sleep Wake Scale (ASWS) - OS2

    The Adolescent Sleep Wake Scale (ASWS) is a 28-item self-report questionnaire designed to assess sleep quality and sleep-wake patterns in adolescents. The scale includes five behavioral subscales: going to bed, falling asleep, maintaining sleep, reinitiating sleep, and returning to wakefulness. Items are rated on a 6-point Likert scale (1 = always to 6 = never). Higher scores indicate better sleep quality. Total scores range from 28-168.

    Measured: Baseline, 3 months, 6 months and 9 months.

33. Outcome 1.b: fNIRS-Based Effective Brain Connectivity Network (EBCN) Features for ASD/ADHD Prediction - OS1

    Quantitative features extracted from single-layer and multi-layer effective brain connectivity networks using functional near-infrared spectroscopy (fNIRS). These features characterize directional, causal interactions between brain regions using Granger Causality and Dynamic Causal Modelling, generating dimensionless connectivity indices (ranging 0-1) to identify early neurophysiological markers predictive of Autism Spectrum Disorder (ASD) and/or Attention-Deficit/Hyperactivity Disorder (ADHD) diagnosis at 42 months of age.

    Measured: Baseline (6 months corrected age), 12 months, 18 months, and 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1. First posted6 May 2026
2. Study start1 Aug 2026 (estimated)
3. Primary completion31 Dec 2028 (estimated)
4. Study completion31 Dec 2028 (estimated)

Resources

• Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
• Other trials for ADHD - Attention Deficit Disorder With HyperactivityStudies of the same condition, open and under way.
• What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.