NCT05329441 · University of California, Los Angeles
Inflammatory and Glutamatergic Mechanisms of Sustained Threat in Adolescents With Depression
(TIGER)
What this study is about
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).
View original scientific description
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.
Interventions
BEHAVIORAL
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.
Primary outcome measures
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
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- All sexes and genders
- All ethnicities
- 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)
Exclusion criteria
- 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
Where
- Los Angeles, California
Collaborators
University of Southern California, University of California, Irvine, Columbia University, Mayo Clinic, University of California, San Francisco, National Institute of Mental Health (NIMH)
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced May 29, 2026 · Source of record for eligibility and locations