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

Официальное название

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

Обзор

The PUREMIND OS1/OS2 study is a multinational, prospective, longitudinal observational study designed to identify early neurophysiological, biological, environmental, and psychosocial markers associated with neurodevelopmental and mental health conditions from infancy through young adulthood. Observational Study 1 (OS1) follows infants and toddlers at high risk for Autism Spectrum Disorder (ASD) and Attention-Deficit/Hyperactivity Disorder (ADHD) to discover biomarkers predictive of later clinical diagnosis, using EEG, fNIRS, psychometric assessments, and biological samples. Observational Study 2 (OS2) includes children, adolescents, and young adults with ASD, ADHD, or Developmental Coordination Disorder (DCD) to identify environmental and biological factors causally linked to anxiety and depression symptoms, and to support the development of personalised criteria for evidence-based interventions. Approximately 800 participants will be recruited across 10 international clinical sites. The study aims to generate multi-domain data to support predictive modelling and inform future personalised mental-health prevention strategies across childhood and young adulthood.

Подробное описание

The PUREMIND study is part of a 4-year Horizon Europe consortium aiming to develop the first Integrated Mental Healthcare Ecosystem (IMHE) for preventing mental health conditions across the life course. The protocol describes two complementary observational components (OS1 and OS2) whose data will underpin predictive modelling of neurodevelopmental and mental-health trajectories.

Observational Study 1 (OS1) OS1 is a 42-month prospective longitudinal cohort study of infants at elevated risk for ASD or ADHD due to prematurity, hypoxic-ischaemic encephalopathy, or perinatal asphyxia, along with a term-born comparison group. The aim is to identify early neurophysiological and behavioural biomarkers detectable before 18 months of age and predictive of later ASD/ADHD diagnoses.

Participants complete five study visits at 6, 12, 18, 24, and 42 months, including:

Demographic and clinical data collection Psychometric and developmental assessments EEG and fNIRS neurophysiology paradigms Stool and urine sampling for metabolomics and microbiome analyses Dietary intake questionnaires A clinical diagnosis of ASD/ADHD is established at 42 months.

OS1 data will enable the extraction of multilayer Effective Brain Connectivity Networks (EBCNs) and the identification of causal neural features using graph-theoretical and machine-learning models.

Observational Study 2 (OS2) OS2 is a 9-month longitudinal study with repeated assessments every 3 months in children (5-10), adolescents (11-18), and young adults (19-25) with clinical diagnoses of ASD, ADHD, or DCD-populations at high risk for anxiety and depression. The aim is to model the dynamic interaction between personal natural environmental (PNE) factors, gene-gut-brain (GGB) mechanisms, and mental-health outcomes (the PNE-GGB-MH process).

Data collection includes:

Demographic, clinical, and psychosocial measures Physical assessments Psychometric testing of anxiety, depression, executive function, and related constructs Stool, urine, and buccal swab samples for metabolomics, microbiome, and DNA-methylation analyses At-home monitoring via the MindMe app (behavioural, environmental, contextual data) Food frequency and dietary questionnaires relevant to epigenetic assays

OS2 uses machine learning and system-identification modelling to identify causal environmental factors contributing to symptom severity and progression, ultimately supporting the development of personalised selection criteria for evidence-based mental-health interventions.

Overall Study Design \& Setting The study is conducted across 10 clinical and academic sites in the UK, Ireland, Italy, Spain, Germany, Romania, Ethiopia, and Bangladesh. A total sample of \~800 participants is planned (400 infants/toddlers; 400 youths/young adults). Data are stored in the secure PUREMIND Central Server Platform, compliant with GDPR and HL7/FHIR standards.

The combined OS1 and OS2 datasets will support predictive models integrating neurophysiology, genetics, epigenetics, metabolomics, microbiome profiles, environmental exposures, and psychosocial factors. While no intervention is delivered within this protocol, findings are intended to guide future personalised, evidence-based prevention and mental-health support strategies.

Первичные конечные точки

• EEG-Based Effective Brain Connectivity Network (EBCN) Features for ASD/ADHD Prediction - OS1 [Срок оценки: Baseline (6 months corrected age), 12 months, 18 months, and 24 months]
• Effective Brain Connectivity Networks (EBCN) Features for ASD/ADHD Prediction - OS1 [Срок оценки: Baseline (6 months corrected age), 12 months, 18 months, and 24 months]
• Clinical Diagnosis of ASD and/or ADHD - OS1 [Срок оценки: 42 months (corrected age)]
• DNA Methylation Profiles from Buccal Swabs - OS1 and OS2 [Срок оценки: Baseline (6 months corrected age), 12 months, 18 months, and 24 months for OS1. Baseline, 3 months, 6 months and 9 months for OS2]
• Metabolomic Signatures from Stool and Urine - OS1 and OS2 [Срок оценки: Baseline (6 months corrected age), 12 months, 18 months, and 24 months for OS1. Baseline, 3 months, 6 months and 9 months for OS2]
• Shotgun Metagenomic Microbiome Profiles from Stool - OS1 and OS2 [Срок оценки: Baseline (6 months corrected age), 12 months, 18 months, and 24 months for OS1. Baseline, 3 months, 6 months and 9 months for OS2]
• General Cognitive Development - OS1 [Срок оценки: Baseline (6 months corrected age), 12 months, 18 months, 24 months, and 42 months]
• Attention Function - OS1 [Срок оценки: Baseline (6 months corrected age), 12 months, 18 months, 24 months, and 42 months]
• Temperament Assessment - OS1 [Срок оценки: Baseline (6 months corrected age), 12 months, 18 months, 24 months, and 42 months]
• Anxiety Symptoms - OS1 [Срок оценки: Baseline (6 months corrected age), 12 months, 18 months, 24 months, and 42 months]

Критерии участия

OS1 Inclusion Criteria:

• Infants born very preterm (<32 weeks) or extremely preterm (<28 weeks); or
• Term-born infants with documented perinatal asphyxia and hypoxic-ischaemic encephalopathy (HIE); or
• Term-born infants with no risk factors (comparison group).
• Must be ≤12 months corrected age at enrolment.

OS1 Exclusion Criteria:

• Syndromic, chromosomal, or known genetic conditions.
• Motor impairments that would prevent participation in psychometric or neurophysiology assessments.

OS2 Inclusion Criteria:

• Individuals aged 5-25 years.
• Clinical diagnosis of ASD, ADHD, or Developmental Coordination Disorder (DCD).
• Able to participate in scheduled assessments.

OS2 Exclusion Criteria:

• Severe motor impairments that limit psychometric assessment.
• Diagnosis of schizophrenia, due to confounding neurocognitive effects.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Великобритания · 1 центр

• University of Exeter — Exeter

Идентификаторы

NCT: NCT07570381 · 24-25-44 · 355570

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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