Recording Stress Biomarkers in Autism Spectrum Disorders (STRESSDEFIS)

Biophysiological Characterization of Stress in Autism Spectrum Disorders: Analysis of Peripheral Markers of the ANS and the HPA Axis

The goal of this observational study is to learn how stress affects children and young people with autism spectrum disorder (ASD). Many individuals with autism experience strong stress reactions that may lead to challenging behaviours such as agitation, withdrawal, aggression, or self-injury. These behaviours can be difficult to predict, especially in people who have limited communication abilities.

Researchers want to better understand how the body reacts to stress in real-life situations. The study focuses on two main biological systems involved in the stress response:

the autonomic nervous system, which produces fast reactions such as changes in heart rate and sweating, and the hypothalamic-pituitary-adrenal axis, which produces slower hormonal responses such as cortisol.

The main questions the study aims to answer are:

• Do physiological stress signals differ between individuals with ASD and those without ASD?
• Are there differences in physiological stress responses between individuals with ASD and non-ASD participants?
• Can physiological markers help identify stress earlier in people with autism?

Researchers will compare children and young people with autism to a control group of participants without autism to see whether their stress responses differ.

Participants will take part in monitoring during their normal daily activities. This allows researchers to observe stress responses in natural environments such as school, home, or specialized care institutions.

Participants will:

• Wear a wrist device during the day that measures heart rate, heart rate variability, skin conductance, skin temperature, and movement
• Provide saliva samples in the morning and afternoon to measure stress hormones such as cortisol and alpha-amylase
• Have additional saliva samples collected after behavioural crises or stressful events when possible
• Be observed by a trained researcher who records behavioural events and the surrounding context

Researchers will combine physiological data, behavioural observations, and contextual information such as physical activity, environmental conditions, and daily routines. This will help identify patterns of stress in everyday life.

The results of this study may help researchers better understand the physiology of stress in autism and support the future development of wearable systems that could detect stress early and help prevent behavioural crises.

Study Overview

• Status: Recruiting
• Conditions: Autism Spectrum Disorder With Intellectual Deficiency

• Study Type: Observational
• Enrollment (Estimated): 60

Contacts and Locations

• Study Contact: Name: Susanne THÜMMLER, MDC- HDR -PhD; Phone Number: +33 4 92 03 03 26; Email: Susanne.THUMMLER@univ-cotedazur.fr

Study Locations

• France
  • Nice, France, 06100
    • Recruiting
    • CoBTEk
    • Contact: Susanne THÜMMLER, MDC- HDR -PhD; Phone Number: +33 4 92 03 03 26; Email: Susanne.THUMMLER@univ-cotedazur.fr

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

The study population consists of children and adolescents aged 3 to 22 years. Two groups are included: individuals diagnosed with autism spectrum disorder (ASD) presenting recurrent behavioral crises, and a neurotypical control group without neurodevelopmental disorders. Participants with ASD are recruited from specialized medico-social institutions providing care and educational support for individuals with neurodevelopmental conditions. Control participants are recruited from the general population through community outreach and school-based information to families.

Participants are observed during their regular daily activities in naturalistic environments such as specialized institutions, schools, or home settings. Continuous physiological monitoring, behavioral observation, and biological sampling are conducted during daytime institutional sessions.

Description

1. Autism Spectrum Disorder (ASD) Group Inclusion Criteria

   • Age between 3 and 22 years
   • Clinical diagnosis of autism spectrum disorder according to established diagnostic criteria
   • Presence of recurrent behavioral crises (minimum of three episodes per week)
   • Enrollment in a participating institution or care structure
   • Written informed consent provided by a parent or legal guardian
   • Assent from the participant when developmentally appropriate

   Exclusion Criteria:

   • Known cardiac or homonal disorders that may interfere with physiological monitoring
   • Lack of consent from parents or legal guardians

2. Control Group (Neurotypical Participants) Inclusion Criteria

   • Age between 3 and 22 years
   • No diagnosis of autism spectrum disorder or other neurodevelopmental disorder
   • No history of major psychiatric or neurological disorders
   • Written informed consent provided by a parent or legal guardian
   • Assent from the participant when developmentally appropriate

Exclusion Criteria

• Known cardiac or hormonal disorders affecting physiological measurements
• Current diagnosis of neurodevelopmental or psychiatric disorder
• Lack of parental or guardian consent

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Autism Spectrum Disorder Participants; The cohort includes children and adolescents aged 3 to 22 years with a clinical diagnosis of autism spectrum disorder (ASD). Participants are recruited from specialized medico-social institutions providing care and educational support for individuals with neurodevelopmental disorders. To be eligible for inclusion, participants must present frequent challenging behaviours, defined as at least three behavioural crises per week (e.g., agitation, aggression, self-injurious behaviours, or severe emotional dysregulation). Participants must also be able to tolerate the placement of a wearable physiological monitoring device during daytime activities. Participants with known cardiac disorders or hormonal disorders that may affect physiological stress measurements are excluded. Written informed consent is obtained from parent
Neurotypical Participants; The control cohort includes children and adolescents aged 3 to 22 years from the general population. Participants in this group do not have a diagnosis of autism spectrum disorder or other neurodevelopmental disorders. Control participants are recruited through community outreach, schools and information provided to families. They are selected to be comparable to the ASD group in terms of age and sex as closely as possible. Participants with known cardiac disorders or hormonal disorders that may affect physiological stress measurements are excluded. Written informed consent is obtained from parents or legal guardians prior to participation. The control participants follow the same monitoring procedures as the ASD group during their usual daily activities.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Autonomic Physiological Stress Markers During Behavioral Stress Episodes	Continuous autonomic physiological signals are recorded using a wearable device during daytime monitoring. The primary outcome consists of variations in autonomic stress markers including heart rate (HR), heart rate variability (HRV), and electrodermal activity (EDA) in relation to behavioral stress events and crisis episodes recorded during observation. These physiological signals will be analyzed to identify changes associated with stress states and behavioral dysregulation in naturalistic settings.	Continuous monitoring during the 4-day observation period (approximately 8 hours per day).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Salivary Cortisol Concentration	Salivary cortisol levels are measured as a biomarker of hypothalamic-pituitary-adrenal (HPA) axis activation. Samples are collected twice daily (morning and afternoon) and after behavioral crisis events when feasible. Cortisol concentrations are quantified using enzyme-linked immunosorbent assay (ELISA) techniques.	Collected during the 4-day observation period (morning, afternoon, and post-crisis when applicable).
Salivary Alpha-Amylase Activity	Salivary alpha-amylase activity is measured as an indicator of sympathetic nervous system activation. Samples are collected using passive saliva swabs and analyzed using a kinetic enzymatic assay.	Collected during the 4-day observation period (morning, afternoon, and post-crisis when applicable).
Frequency and Duration of Behavioral Stress Episodes	Behavioral stress indicators and crisis episodes are recorded using a structured Antecedent-Behavior-Consequence (ABC) observation grid completed by the investigator during the monitoring period. Outcomes include the frequency and duration of behavioral dysregulation events such as agitation, self-injurious behavior, aggressive behavior, withdrawal, and emotional distress	Recorded continuously during the 4-day observation period.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Behavioral Problems Inventory (BPI) Scores	Parents complete the Behavioral Problems Inventory (BPI) questionnaire to assess the frequency and severity of self-injurious, stereotyped, and aggressive behaviors in everyday life. The BPI provides a standardized behavioral profile for each participant.	Assessed at baseline.
Nonverbal Cognitive Functioning	Nonverbal cognitive ability is assessed using the Leiter International Performance Scale - Third Edition (Leiter-3), a nonverbal intelligence test designed for individuals aged 3 to 75 years and suitable for participants with communication difficulties.	Assessed Day 1.
Adaptive Functioning	Adaptive functioning is evaluated using the Vineland Adaptive Behavior Scales, which measure communication, daily living skills, socialization, and motor skills through caregiver interview or questionnaire.	Assessed at baseline.

Collaborators and Investigators

• Sponsor: Universite Cote d'Azur

Study record dates

Study Major Dates

• Study Start (Actual): March 23, 2026
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: March 13, 2026
• First Submitted That Met QC Criteria: April 14, 2026
• First Posted (Actual): April 17, 2026

Study Record Updates

• Last Update Posted (Actual): April 23, 2026
• Last Update Submitted That Met QC Criteria: April 20, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: autism spectrum disorder; autonomic nervous system; heart rate variability; salivary cortisol; salivary alpha amylase; ecological assessment; skin conductance; hypothalamic-pituitary-adrenal axis; stress biomarkers; challenging behavior; profound autism
• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Autism Spectrum Disorder
• Other Study ID Numbers: 25.03788.000456

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

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