Depression in AdolescenceTIGERNCT05329441
Inflammatory and Glutamatergic Mechanisms of Sustained Threat in Adolescents With Depression
An observational study of Depression in Adolescence, run by University of California, Los Angeles at 1 site in United States.
Trial summary
Despite the prevalence and significant public health concern over depression among adolescents, up to 40% of depressed adolescents do not respond to first-line antidepressants (herein termed treatment non-response, TNR). Read more about this study
- Who is it for?
- Ages 14 to 21 years
- Conditions the study is for
- Depression in Adolescence
- What is being tested?
- Trier Social Stress Test (TSST)
- Type of treatment
- Lifestyle or therapy programme
- How many people
- 160 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Jul 2023to 30 Apr 2028
- Phase
- Observational
- 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 14 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: Adolescents presenting to school counseling centers, community clinics, and/or medical centers (primary care, psychiatry, etc)
Who may be able to join
- All sexes and genders
- All ethnicities
- Ages 14-21
- Postpubertal (Tanner stage > 3)
- No medications that will interfere with the study (including antidepressants, mood stabilizers, hormone supplements, steroids, etc.) for at least 2-6 weeks (depending on exact medication)
- Currently being seen by a clinician who will treat the participant with fluoxetine or escitalopram
- The ability to provide assent, understand, and complete all study procedures
- Caregiver consent (if applicable)
Who cannot join
- Primary mental health diagnosis other than a depressive disorder according to DSM-V
- Any contraindications to MRI scanning, phlebotomy, or SSRI treatment
- Stimulant usage
- A concussion within the last 6 weeks or any lifetime concussion with loss of consciousness for at least 10 minutes
- Any inflammatory conditions or use of anti-inflammatory medications that may influence study findings
- Any major neurological or developmental disorders which could impact the participant's ability to comply with study procedure
- Meeting for current or lifetime criteria of mania or psychosis, diagnosis of bipolar disorder, or any substance use disorders
- First-degree relative with current, past, or suspected mania or psychosis
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Cheryl Sun, B.A. contact
United States1 site, 1 recruiting
- Recruiting
University of California, Los Angeles
Los Angeles, California, 90095
Tiffany Ho, Ph.D., 310-825-0561
Tiffany C Ho, Ph.D.
About this study
Official title: Inflammatory and Glutamatergic Mechanisms of Sustained Threat in Adolescents With Depression: Toward Predictors of Treatment Response and Clinical Course
Despite the prevalence and significant public health concern over depression among adolescents, up to 40% of depressed adolescents do not respond to first-line antidepressants (herein termed treatment non-response, TNR). The goal of this project is to recruit and assess 160 treatment-seeking depressed adolescents and test whether acute stress impacts peripheral levels of inflammation and downstream levels of glutamate in corticolimbic regions previously associated with depression, whether these stress-related biomarkers predict TNR to a 12-week trial of either fluoxetine or escitalopram, and whether these stress-related biomarkers predict 18-month clinical course.
Read the detailed description
Despite the prevalence and public health significance of depression, up to 40% of depressed adolescents do not respond to first-line antidepressants (i.e., serotonin selective reuptake inhibitors [SSRIs]). Adolescents with treatment non-response (TNR) are at high risk for physical and mental health difficulties associated with ineffectively treated depression, including cardiovascular disease and suicide. Thus, identifying the neurobiological mechanisms that underlie TNR in adolescents is a critical step toward optimizing treatment plans for those who do not respond to first-line treatments. In this context, sustained threat to social stressors, as measured by elevated inflammatory profiles to stressful stimuli, has been shown to drive the onset and maintenance of depression among adolescents and is associated with TNR. The mechanisms by which elevated inflammation impact the brain in depressed adolescents, however, are unclear. To address these gaps in our knowledge, the investigators will test the central hypothesis that excessive glutamate (Glu) in depression-related corticolimbic circuits-including the anterior cingulate cortex, ventromedial prefrontal cortex, amygdala, and hippocampus-is a critical mediator between peripheral inflammation and TNR in depressed adolescents. Specifically, the investigators will conduct a prospective 18-month study of 160 unmedicated treatment-seeking depressed adolescents using state-of-the-art multimodal neuroimaging data at 7 Tesla. At Time 1 (prior to SSRI treatment) and Time 2 (after an open-label 12-week SSRI trial), the investigators will assess peripheral measures of pro-inflammatory cytokines and glutamate in corticolimbic circuits before and after a well-validated adolescent-version of the Trier Social Stress Test (TSST). At Time 1, the investigators will test if TSST induces increases in inflammation and glutamate in corticolimbic circuits in unmedicated adolescents with depression. At Time 2, the investigators will use machine learning methods to identify multi-level predictors of TNR based on behavioral, inflammatory, and neural indicators of sustained threat to social stress; the investigators will also test whether glutamate in corticolimbic circuits mediates the association between baseline levels of inflammation and TNR. Finally, as an exploratory aim, the investigators will continue to clinically assess depression symptoms and collect information on social stressors (e.g., context, severity, duration) every 3 months for 15 months following Time 2 (i.e., from Time 3 to Time 7), which will enable the use of functional clustering analyses to identify subgroups of adolescents on the basis of depression trajectories (e.g., persistent depression, gradual remission, etc), and identify predictors of these subgroups and other related clinical outcomes (e.g., remission status), while accounting for the effects of TNR status and any changes in treatment (and other related factors, including stressful life events). Results from this work will motivate future studies testing alternative therapeutics for depressed adolescents at risk for treatment resistant depression.
- Conditions
- Depression in Adolescence
- Being tested
- Trier Social Stress Test (TSST)
- Keywords
- depression, adolescence
- Medical subject headings
- Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Trier Social Stress Test (TSST)Behavioural
In this mechanistic study, all participants will undergo a modified version of the Trier Social Stress Test (TSST), which is a well-validated psychosocial stress paradigm, adapted for adolescents that involves no deception and is considered a very mild stressor. The TSST comprises of two stress tests: a 5-minute arithmetic task and a 5-minute speech task. Due to repeated testing of the TSST, participants will be randomized to one task at T1 and complete the second task at T2 (counterbalanced design). Every 5 minutes, participants will provide ratings of their mood using a visual analogue scale (1-10) of eight mood states (Afraid, Confused, Sad, Angry, Energetic, Tired, Happy, and Tense) that will be used as potential behavioral responses to social stress. Glutamate and inflammation outcomes will be examined acutely and from T1 and T2.
| Study group | Role | What they receive |
|---|---|---|
| Study Participants | All depressed participants will undergo the same study procedures Receives: Behavioral: Trier Social Stress Test (TSST) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Children's Depressing Rating Scale-Revised
Clinician-administered assessment of depression severity (dimensional) assessment of depression Clinician-administered assessment of depression severity (dimensional)
Measured: baseline and 12-week follow-up
Reynolds Adolescent Depression Scale-2 (RADS-2)
Self-report measure of depression severity (dimensional)
Measured: baseline and 12-week follow-up
Kiddie Schedule for Affective Disorders and Schizophrenia (KSADS-PL)
The K-SADS-PL is a semi-structured clinical interview designed to yield reliable and valid diagnoses of current and past history of Axis I disorders in children and adolescents. We will use the K-SADS-PL to determine whether a participant is currently depressed, in remission, experiencing relapse or a recurrent episode. From this interview, we will also obtain information such as age of depression onset, number of depressive episodes, medication and therapy usage and changes, etc
Measured: baseline and 12-week follow-up
Secondary outcomes (2)
Patient Health Questionnaire-9
Self-report measure of depression severity (dimensional) used for adults (which will facilitate cross-study comparisons)
Measured: baseline and 12-week follow-up
Mood Ratings on the Trier Social Stress Test
Visual analogue scale of feeling Afraid, Confused, Sad, Angry, Energetic, Tired, Happy, and Tense from 0 [nothing] to 10 [a bit]
Measured: Acute (baseline and throughout study procedures)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2022
- Study start6 Jul 2023
- Primary completion1 Apr 2028 (estimated)
- Study completion30 Apr 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Depression in AdolescenceStudies of the same condition, open and under way.
- More trials run by University of California, Los AngelesThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 160 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of California, Los Angeles
- Sponsor type
- University, hospital or other
- Collaborators
- University of Southern California, University of California, Irvine, Columbia University, Mayo Clinic, University of California, San Francisco, National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Tiffany Cheing Ho, PhD, University of California, Los Angeles
- Investigators
- Tiffany Ho, Ph.D., Principal investigator, University of California, Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05329441
- Sponsor's protocol ID
- TIGER R01
- Other IDs
- R01MH127176
- Acronym
- TIGER
- Status last verified
- May 2026
- First submitted
- 8 Apr 2022
- Last updated
- 29 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Anonymized demographic and clinical data as well as anonymized curated (i.e., after preprocessing and quality control) MRI-based metrics and cytokine levels
Publications
Coury SM, Lopez V, Bajwa Z, Garcia JM, Teresi GI, Kuhlman KR, Li Y, Cole S, Miklowitz DJ, Pappas I, Ho TC. Protocol for teen inflammation glutamate emotion research (TIGER): Toward predictors of treatment response and clinical course in depressed adolescents. Brain Behav Immun Health. 2023 Dec 20;35:100718. doi: 10.1016/j.bbih.2023.100718. eCollection 2024 Feb.
PubMed 38235411
Study at a glance
From the registry record, last updated by the sponsor on 29 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Inflammatory and Glutamatergic Mechanisms of Sustained Threat in Adolescents With Depression: Toward Predictors of Treatment Response and Clinical Course
- ClinicalTrials.gov ID
- NCT05329441
- Acronym / sponsor ID
- TIGER / TIGER R01
- Conditions
- Depression in Adolescence
- Keywords
- depression, adolescence
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 160 participants (estimated)
- Lead sponsor
- University of California, Los AngelesUniversity, hospital or other
- Collaborators
- University of Southern California, University of California, Irvine, Columbia University, Mayo Clinic, University of California, San Francisco, National Institute of Mental Health (NIMH)
- Study start
- 6 Jul 2023 (actual)
- Primary completion
- 1 Apr 2028 (estimated)
- Study completion
- 30 Apr 2028 (estimated)
- First posted
- 15 Apr 2022 (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.
Despite the prevalence and significant public health concern over depression among adolescents, up to 40% of depressed adolescents do not respond to first-line antidepressants (herein termed treatment non-response, TNR). The goal of this project is to recruit and assess 160 treatment-seeking depressed adolescents and test whether acute stress impacts peripheral levels of inflammation and downstream levels of glutamate in corticolimbic regions previously associated with depression, whether these stress-related biomarkers predict TNR to a 12-week trial of either fluoxetine or escitalopram, and whether these stress-related biomarkers predict 18-month clinical course.
Detailed description
Despite the prevalence and public health significance of depression, up to 40% of depressed adolescents do not respond to first-line antidepressants (i.e., serotonin selective reuptake inhibitors [SSRIs]). Adolescents with treatment non-response (TNR) are at high risk for physical and mental health difficulties associated with ineffectively treated depression, including cardiovascular disease and suicide. Thus, identifying the neurobiological mechanisms that underlie TNR in adolescents is a critical step toward optimizing treatment plans for those who do not respond to first-line treatments. In this context, sustained threat to social stressors, as measured by elevated inflammatory profiles to stressful stimuli, has been shown to drive the onset and maintenance of depression among adolescents and is associated with TNR. The mechanisms by which elevated inflammation impact the brain in depressed adolescents, however, are unclear. To address these gaps in our knowledge, the investigators will test the central hypothesis that excessive glutamate (Glu) in depression-related corticolimbic circuits-including the anterior cingulate cortex, ventromedial prefrontal cortex, amygdala, and hippocampus-is a critical mediator between peripheral inflammation and TNR in depressed adolescents. Specifically, the investigators will conduct a prospective 18-month study of 160 unmedicated treatment-seeking depressed adolescents using state-of-the-art multimodal neuroimaging data at 7 Tesla. At Time 1 (prior to SSRI treatment) and Time 2 (after an open-label 12-week SSRI trial), the investigators will assess peripheral measures of pro-inflammatory cytokines and glutamate in corticolimbic circuits before and after a well-validated adolescent-version of the Trier Social Stress Test (TSST). At Time 1, the investigators will test if TSST induces increases in inflammation and glutamate in corticolimbic circuits in unmedicated adolescents with depression. At Time 2, the investigators will use machine learning methods to identify multi-level predictors of TNR based on behavioral, inflammatory, and neural indicators of sustained threat to social stress; the investigators will also test whether glutamate in corticolimbic circuits mediates the association between baseline levels of inflammation and TNR. Finally, as an exploratory aim, the investigators will continue to clinically assess depression symptoms and collect information on social stressors (e.g., context, severity, duration) every 3 months for 15 months following Time 2 (i.e., from Time 3 to Time 7), which will enable the use of functional clustering analyses to identify subgroups of adolescents on the basis of depression trajectories (e.g., persistent depression, gradual remission, etc), and identify predictors of these subgroups and other related clinical outcomes (e.g., remission status), while accounting for the effects of TNR status and any changes in treatment (and other related factors, including stressful life events). Results from this work will motivate future studies testing alternative therapeutics for depressed adolescents at risk for treatment resistant depression.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Study Participants | – | Behavioral: Trier Social Stress Test (TSST)All depressed participants will undergo the same study procedures |
Who may qualify
- Ages
- 14 to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- Adolescents presenting to school counseling centers, community clinics, and/or medical centers (primary care, psychiatry, etc)
Key inclusion criteria (8 listed)
- All sexes and genders
- All ethnicities
- Ages 14-21
- Postpubertal (Tanner stage > 3)
- No medications that will interfere with the study (including antidepressants, mood stabilizers, hormone supplements, steroids, etc.) for at least 2-6 weeks (depending on exact medication)
Key exclusion criteria (8 listed)
- Primary mental health diagnosis other than a depressive disorder according to DSM-V
- Any contraindications to MRI scanning, phlebotomy, or SSRI treatment
- Stimulant usage
- A concussion within the last 6 weeks or any lifetime concussion with loss of consciousness for at least 10 minutes
- Any inflammatory conditions or use of anti-inflammatory medications that may influence study findings
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 |
|---|---|---|
| Trier Social Stress Test (TSST)In this mechanistic study, all participants will undergo a modified version of the Trier Social Stress Test (TSST), which is a well-validated psychosocial stress paradigm, adapted for adolescents that involves no deception and is considered a very mild stressor. The TSST comprises of two stress tests: a 5-minute arithmetic task and a 5-minute speech task. Due to repeated testing of the TSST, participants will be randomized to one task at T1 and complete the second task at T2 (counterbalanced design). Every 5 minutes, participants will provide ratings of their mood using a visual analogue scale (1-10) of eight mood states (Afraid, Confused, Sad, Angry, Energetic, Tired, Happy, and Tense) that will be used as potential behavioral responses to social stress. Glutamate and inflammation outcomes will be examined acutely and from T1 and T2. | Behavioural | Study Participants |
Primary outcome
Children's Depressing Rating Scale-Revised
Time frame: baseline and 12-week follow-up
Clinician-administered assessment of depression severity (dimensional) assessment of depression Clinician-administered assessment of depression severity (dimensional)
Reynolds Adolescent Depression Scale-2 (RADS-2)
Time frame: baseline and 12-week follow-up
Self-report measure of depression severity (dimensional)
Kiddie Schedule for Affective Disorders and Schizophrenia (KSADS-PL)
Time frame: baseline and 12-week follow-up
The K-SADS-PL is a semi-structured clinical interview designed to yield reliable and valid diagnoses of current and past history of Axis I disorders in children and adolescents. We will use the K-SADS-PL to determine whether a participant is currently depressed, in remission, experiencing relapse or a recurrent episode. From this interview, we will also obtain information such as age of depression onset, number of depressive episodes, medication and therapy usage and changes, etc
2 secondary outcomes
Patient Health Questionnaire-9
Time frame: baseline and 12-week follow-up
Mood Ratings on the Trier Social Stress Test
Time frame: Acute (baseline and throughout study procedures)
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 29 May 2026.
- Derived from this study: PubMed 38235411Coury SM, Lopez V, Bajwa Z, Garcia JM, Teresi GI, Kuhlman KR, Li Y, Cole S, Miklowitz DJ, Pappas I, Ho TC. Protocol for teen inflammation glutamate emotion research (TIGER): Toward predictors of treatment response and clinical course in depressed adolescents. Brain Behav Immun Health. 2023 Dec 20;35:100718. doi: 10.1016/j.bbih.2023.100718. eCollection 2024 Feb.
- Individual participant dataSharing planned: Yes. Anonymized demographic and clinical data as well as anonymized curated (i.e., after preprocessing and quality control) MRI-based metrics and cytokine levels
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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.
Cheryl Sun, B.A. contact
Tiffany Ho, Ph.D. principal investigator
University of California, Los Angeles
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Depression in Adolescence, run by University of California, Los Angeles 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?
The sponsor lists 8 inclusion and 8 exclusion criteria. 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 29 May 2026. 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 Tiffany Ho, Ph.D. (310-825-2961, tiffany.ho@psych.ucla.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Children's Depressing Rating Scale-Revised (time frame: baseline and 12-week follow-up). 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?
On the ClinicalTrials.gov record for NCT05329441, which also lists 1 linked publication.
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 29 May 2026.