Major Depressive DisorderNCT06816329
Stress Dynamics and Familial Risk for Depression in Female Adolescents
A study testing Computer Task Manipulation in people with Major Depressive Disorder, run by Mclean Hospital at 1 site in United States.
Trial summary
Stress and a parental history of major depressive disorder (MDD) are among the strongest risk factors for future development of MDD. Studies have shown that having a parental history of MDD may be associated with behavioral, psychophysiological, and hormonal responses to stress that are associated with poorer stress… Read more about this study
- Who is it for?
- Ages 13 to 15 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- Computer Task Manipulation
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 148 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Oct 2025to 31 Mar 2030
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 13 to 15 years
- Women only
- Healthy volunteers accepted
- Child
Inclusion Criteria: General Inclusion Criteria for all Adolescent Cohorts:
- Female sex assigned at birth
- Ages 13-15
- English as first language or English Fluency
- Right-handed
- Have a personal cell phone to complete the ecological momentary assessments
- Ability to give signed, informed consent/assent either written or electronic (via RedCap eConsent)
- Normal or corrected to normal vision and hearing
Additional Inclusion Criteria for Female Adolescents with a Parental History of MDD, high-risk group:
- A biological parent meeting DSM-5 criteria for at least one past/current major depressive episode
Exclusion Criteria: General Exclusion Criteria for all Adolescent Cohorts:
- Presence of any contraindication for MRI:
- Cardiac pacemakers
- Metal clips on blood vessels (also called stents)
- Artificial heart valve, artificial arms, hands, legs, etc.
- Brain stimulator devices
- Implanted drug pumps
- Ear or eye implants
- Known metal fragments in eyes
- Exposure to metal filings or shrapnel (sheet metal workers, welders, and others)
- Other metallic surgical hardware in vital area
- Certain tattoos with metallic ink
- Certain intrauterine devices (IUDs) containing metal
- Any other metallic objects that are deemed a contraindication to MRI that cannot be removed
- Certain transdermal (skin) patches such as:
NicoDerm (nicotine for tobacco dependence) Transderm Scop (scopolamine for motion sickness) Ortho Evra (birth control)
- Presence of medical or neurological illness that could impact fMRI measures of cerebral blood flow (e.g., head injury resulting in loss of consciousness greater than 5 minutes, seizure, tic disorder, serious/unstable cardiac, hepatic, renal, respiratory, endocrine, neurologic or hematologic illnesses)
- Clinical/Laboratory Evidence of Hypothyroidism or Hyperthyroidism
- Use of hormonal replacement therapy, anabolic steroids
- Lifetime history of electroconvulsive therapy
- Current tobacco product use
- Lifetime use of any psychotropic medication
- Clinically significant levels of depressive symptoms according to the Children's Depression Rating Scale-Revised (T Score > 54, Poznanski et al., 1996)
- Diagnosis of a neurodevelopmental disorder (e.g., Autism Spectrum Disorder, Learning Disorder w/ impairment in reading) that would interfere with study tasks (e.g., understanding and completing lengthy battery of questionnaires, ability to complete fMRI scan session and tasks without moving)
Additional Exclusion Criteria for Female Adolescents with a Parental History of MDD, high-risk group:
- Lifetime or current Diagnostic and Statistical Manual (DSM)-5 diagnoses of MDD, persistent depressive disorder, schizophrenia spectrum or other psychotic disorder, bipolar disorder, substance/alcohol use disorder, eating disorders, and posttraumatic stress disorder
Additional Exclusion Criteria for Female Adolescents without a Parental History of MDD, low-risk group:
- Any past or current Diagnostic and Statistical Manual (DSM)-5 psychiatric or substance/alcohol use disorder
- First-degree relative history of any psychiatric disorder
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
McLean Hospital
Belmont, Massachusetts, 02478
Emily Belleau, Ph.D., 617-855-4245, ebelleau@mclean.harvard.edu
Emily Belleau, Ph.D.
About this study
Official title: Tracking the Dynamic Trajectory of Behavioral, Physiological, and Neurobiological Stress Responses in Female Adolescents at High and Low Familial Risk for Depression
Stress and a parental history of major depressive disorder (MDD) are among the strongest risk factors for future development of MDD. Studies have shown that having a parental history of MDD may be associated with behavioral, psychophysiological, and hormonal responses to stress that are associated with poorer stress coping. . Adolescence is a vulnerable developmental window linked to increased MDD risk, especially for females, as rates of MDD surge relative to males. Despite the central role of stress in MDD onset, little is known about the brain mechanisms underlying stress responses in susceptible female adolescents at high familial risk for MDD. Also, it is unclear how stress-related brain network alterations may relate to "real-world" maladaptive stress responses and whether these stress-related brain network changes are predictive of future depression onset. We will fulfill these research gaps by combining neuroimaging with intensive longitudinal tracking of depressive symptomology as well as behavioral and physiological responses to "real world" stress using smartphone and smartwatch technology. Elucidating these neural mechanisms may aid in the discovery of MDD biomarkers that could identify youth at greatest risk for future MDD development and lead to earlier intervention efforts.
Read the detailed description
Participants in this research study will include female adolescent between the age of 13 to 15, who may or may not have a parental history of depression. About 148 adolescents will take part in this study along with a biological parent/parent(s) over the next five years.
The study will include five sessions over the span of 18-months, including:
- A clinical diagnostic interview as well as filling out a series of questionnaires and assessments. This can be done virtually over Zoom or in-person.
- The second session will include a functional magnetic resonance imaging (fMRI) brain scan to be conducted at the McLean Hospital Imaging Center. Participants will be asked to respond to surveys on their cell phone in the two-weeks following the fMRI brain scan. Participants will also be given and asked to wear a smartwatch that tracks their heart rate, activity level, and sleep patterns for two-weeks.
- The third session will include a diagnostic interview, assessments, and questionnaires to be completed six-months after the fMRI brain scan. Participants will be asked to complete surveys on their cell phone during the two-weeks following this six month follow-up session. Participants will also be given and asked to wear a smartwatch that tracks their heart rate, activity level, and sleep patterns for two-weeks.
- The fourth session will include a diagnostic interview, assessments, and questionnaires to be completed 12-months after the fMRI brain scan. Participants will be asked to complete surveys on their cell phone during the two-weeks following this 12-month follow-up session. Participants will also be given and asked to wear a smartwatch that tracks their heart rate, activity level, and sleep patterns for two-weeks.
- The fifth session will include a diagnostic interview, assessments, and questionnaires to be completed 18-months after the fMRI brain scan. Participants will be asked to complete surveys on their cell phone during the two-weeks following this 18-month follow-up session. Participants will also be given and asked to wear a smartwatch that tracks their heart rate, activity level, and sleep patterns for two-weeks.
- Conditions
- Major Depressive Disorder
- Being tested
- Computer Task Manipulation
- Keywords
- stress, depression, adolescents, neuroimaging, familial risk
- Medical subject headings
- Depressive Disorder, Major, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Computer Task ManipulationBehavioural
Participants will complete computer tasks.
| Study group | Role | What they receive |
|---|---|---|
| Computer Task Manipulation | Experimental | Participants will complete computer tasks while undergoing an fMRI brain scan. Receives: Behavioral: Computer Task Manipulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time Spent in Default Mode-Frontoparietal Network Coactivation Pattern (CAP)
Time Spent in Default Mode-Frontoparietal Network Coactivation Pattern (CAP). An fMRI variable. (the number of volumes spent in this CAP).
Measured: Throughout a 1.75 hour MRI scan collected during the middle of a 3.5 hour 2nd study session
Persistence in default mode network-frontoparietal network co-activation pattern
Persistence in default mode network-frontoparietal network CAP. An fMRI measure. (the average number of consecutive volumes spent in this CAP)
Measured: Throughout a 1.75 hour MRI scan collected during the middle of a 3.5 hour 2nd study session
Depressive Symptoms
The total score on the Mood and Feelings Questionnaire [Min Score: 0, Max Score: 66, higher scores mean more severe depressive symptoms)
Measured: Collected at baseline, the beginning of a 1.75 hour MRI, and at 6-, 12-, and 18-month follow-ups
Secondary outcomes (5)
Cortisol
Saliva rating to be collected throughout the fMRI brain scan
Measured: Collected throughout a 3.5 hour second study session that involves a 1.75 hour MRI conducted at the middle of the session
Stress Ratings
Stress ratings (0-100 sliding bar scale) collected via smartphone.
Measured: Collected during a two-week period immediately after the 2nd study session (i.e., the MRI session), and then in the two-weeks immediately after the 6-, 12-, and 18-month follow-up sessions, respectively
Average heart rate (beats per minute)
compute average heart rate through smartwatch technology
Measured: Collected during a two-week period immediately after the 2nd study session (i.e., the MRI session), and then in the two-weeks immediately after the 6-, 12-, and 18-month follow-up sessions, respectively
heart rate variability
heart rate variability expressed as the root mean square of successive differences (RMSSD)
Measured: Collected during a two-week period immediately after the 2nd study session (i.e., the MRI session), and then in the two-weeks immediately after the 6-, 12-, and 18-month follow-up sessions, respectively
Sleep duration
sleep duration computed as the difference in minutes between sleep onset and sleep offset
Measured: Collected during a two-week period immediately after the 2nd study session (i.e., the MRI session), and then in the two-weeks immediately after the 6-, 12-, and 18-month follow-up sessions, respectively
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2025
- Study start15 Oct 2025
- Primary completion31 Mar 2030 (estimated)
- Study completion31 Mar 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depressive DisorderStudies 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.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Case-Control Design
- Masking
- None (open label)
- Enrolment
- 148 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mclean Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Emily L. Belleau, Mclean Hospital
- Investigators
- Emily Belleau, Ph.D., Principal investigator, Mclean Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06816329
- Sponsor's protocol ID
- R01MH137441
- Status last verified
- Oct 2025
- First submitted
- 28 Jan 2025
- Last updated
- 23 Oct 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Demographic, clinical, neuroimaging, psychophysiological, ecological momentary assessment, and smartwatch data will be preserved to enable sharing via NDA data of sufficient quality to validate and replicate research findings described in the Aims. NIMH requires data measured from human subjects to be shared using the NDA. All data will be deposited to NDA starting 12 months after the award begins and will be deposited every six months thereafter following the usual NDA data submission dates. Data will be findable for the research community through the NDA Collection that will be established when this application is funded. For all publications, an NDA study will be created. Each of those studies are assigned a digital object identifier (DOI). This data DOI will be referenced in the publication to allow the research community easy access to the exact data used in the publication. The research community will have access to data when the award ends.
Study at a glance
From the registry record, last updated by the sponsor on 23 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tracking the Dynamic Trajectory of Behavioral, Physiological, and Neurobiological Stress Responses in Female Adolescents at High and Low Familial Risk for Depression
- ClinicalTrials.gov ID
- NCT06816329
- Acronym / sponsor ID
- R01MH137441
- Conditions
- Major Depressive Disorder
- Keywords
- stress, depression, adolescents, neuroimaging, familial risk
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 148 participants (estimated)
- Lead sponsor
- Mclean HospitalUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- 15 Oct 2025 (actual)
- Primary completion
- 31 Mar 2030 (estimated)
- Study completion
- 31 Mar 2030 (estimated)
- First posted
- 10 Feb 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Stress and a parental history of major depressive disorder (MDD) are among the strongest risk factors for future development of MDD. Studies have shown that having a parental history of MDD may be associated with behavioral, psychophysiological, and hormonal responses to stress that are associated with poorer stress coping. . Adolescence is a vulnerable developmental window linked to increased MDD risk, especially for females, as rates of MDD surge relative to males. Despite the central role of stress in MDD onset, little is known about the brain mechanisms underlying stress responses in susceptible female adolescents at high familial risk for MDD. Also, it is unclear how stress-related brain network alterations may relate to "real-world" maladaptive stress responses and whether these stress-related brain network changes are predictive of future depression onset. We will fulfill these research gaps by combining neuroimaging with intensive longitudinal tracking of depressive symptomology as well as behavioral and physiological responses to "real world" stress using smartphone and smartwatch technology. Elucidating these neural mechanisms may aid in the discovery of MDD biomarkers that could identify youth at greatest risk for future MDD development and lead to earlier intervention efforts.
Detailed description
Participants in this research study will include female adolescent between the age of 13 to 15, who may or may not have a parental history of depression. About 148 adolescents will take part in this study along with a biological parent/parent(s) over the next five years.
The study will include five sessions over the span of 18-months, including:
- A clinical diagnostic interview as well as filling out a series of questionnaires and assessments. This can be done virtually over Zoom or in-person.
- The second session will include a functional magnetic resonance imaging (fMRI) brain scan to be conducted at the McLean Hospital Imaging Center. Participants will be asked to respond to surveys on their cell phone in the two-weeks following the fMRI brain scan. Participants will also be given and asked to wear a smartwatch that tracks their heart rate, activity level, and sleep patterns for two-weeks.
- The third session will include a diagnostic interview, assessments, and questionnaires to be completed six-months after the fMRI brain scan. Participants will be asked to complete surveys on their cell phone during the two-weeks following this six month follow-up session. Participants will also be given and asked to wear a smartwatch that tracks their heart rate, activity level, and sleep patterns for two-weeks.
- The fourth session will include a diagnostic interview, assessments, and questionnaires to be completed 12-months after the fMRI brain scan. Participants will be asked to complete surveys on their cell phone during the two-weeks following this 12-month follow-up session. Participants will also be given and asked to wear a smartwatch that tracks their heart rate, activity level, and sleep patterns for two-weeks.
- The fifth session will include a diagnostic interview, assessments, and questionnaires to be completed 18-months after the fMRI brain scan. Participants will be asked to complete surveys on their cell phone during the two-weeks following this 18-month follow-up session. Participants will also be given and asked to wear a smartwatch that tracks their heart rate, activity level, and sleep patterns for two-weeks.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Case-Control Design
| Arm | Type | Receives |
|---|---|---|
| Computer Task Manipulation | Experimental | Behavioral: Computer Task ManipulationParticipants will complete computer tasks while undergoing an fMRI brain scan. |
Who may qualify
- Ages
- 13 to 15 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Computer Task ManipulationParticipants will complete computer tasks. | Behavioural | Computer Task Manipulation |
Primary outcome
Time Spent in Default Mode-Frontoparietal Network Coactivation Pattern (CAP)
Time frame: Throughout a 1.75 hour MRI scan collected during the middle of a 3.5 hour 2nd study session
Time Spent in Default Mode-Frontoparietal Network Coactivation Pattern (CAP). An fMRI variable. (the number of volumes spent in this CAP).
Persistence in default mode network-frontoparietal network co-activation pattern
Time frame: Throughout a 1.75 hour MRI scan collected during the middle of a 3.5 hour 2nd study session
Persistence in default mode network-frontoparietal network CAP. An fMRI measure. (the average number of consecutive volumes spent in this CAP)
Depressive Symptoms
Time frame: Collected at baseline, the beginning of a 1.75 hour MRI, and at 6-, 12-, and 18-month follow-ups
The total score on the Mood and Feelings Questionnaire [Min Score: 0, Max Score: 66, higher scores mean more severe depressive symptoms)
5 secondary outcomes
Cortisol
Time frame: Collected throughout a 3.5 hour second study session that involves a 1.75 hour MRI conducted at the middle of the session
Stress Ratings
Time frame: Collected during a two-week period immediately after the 2nd study session (i.e., the MRI session), and then in the two-weeks immediately after the 6-, 12-, and 18-month follow-up sessions, respectively
Average heart rate (beats per minute)
Time frame: Collected during a two-week period immediately after the 2nd study session (i.e., the MRI session), and then in the two-weeks immediately after the 6-, 12-, and 18-month follow-up sessions, respectively
heart rate variability
Time frame: Collected during a two-week period immediately after the 2nd study session (i.e., the MRI session), and then in the two-weeks immediately after the 6-, 12-, and 18-month follow-up sessions, respectively
Sleep duration
Time frame: Collected during a two-week period immediately after the 2nd study session (i.e., the MRI session), and then in the two-weeks immediately after the 6-, 12-, and 18-month follow-up sessions, respectively
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Oct 2025.
- Individual participant dataSharing planned: Yes. Demographic, clinical, neuroimaging, psychophysiological, ecological momentary assessment, and smartwatch data will be preserved to enable sharing via NDA data of sufficient quality to validate and replicate research findings described in the Aims. NIMH requires data measured from human subjects to be shared using the NDA. All data will be deposited to NDA starting 12 months after the award begins and will be deposited every six months thereafter following the usual NDA data submission dates. Data will be findable for the research community through the NDA Collection that will be established when this application is funded. For all publications, an NDA study will be created. Each of those studies are assigned a digital object identifier (DOI). This data DOI will be referenced in the publication to allow the research community easy access to the exact data used in the publication. The research community will have access to data when the award ends.
Related trials for Major Depressive Disorder
Not yet recruiting
Preventive and Personalized Digital Emotion Regulation Skills Intervention to Reduce Depression and Anxiety in Youths With Adverse Childhood Experiences
Adverse Childhood Experience, Depression / Major Depressive Disorder
RecruitingPhase 4
Biomarker-Guided Antidepressant Selection
Depression - Major Depressive Disorder, Treatment-resistant Depression (TRD)
Recruiting
Targeting Network Dysfunction in Apathy of Late-life Depression Using Digital Therapeutics
Major Depressive Disorder, Apathy
RecruitingObservational study
Student Precarity and Psychiatry
Depressive Disorder, Major, Generalized Anxiety Disorder
Not yet recruiting
Acute Intermittent Hypoxia Therapy for Depression
Major Depressive Disorder (MDD)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Emily Belleau, Ph.D. principal investigator
Mclean Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Computer Task Manipulation in people with Major Depressive Disorder, run by Mclean Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 23 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Emily Belleau (617-855-4245, ebelleau@mclean.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time Spent in Default Mode-Frontoparietal Network Coactivation Pattern (CAP) (time frame: Throughout a 1.75 hour MRI scan collected during the middle of a 3.5 hour 2nd study session). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Oct 2025.