Inflammatory and Glutamatergic Mechanisms of Sustained Threat in Adolescents With Depression

NCT05329441 | Recruiting

• 1 other identifier: TIGER R01
• Study Type: observational
• Target: 160
• Locations: 1 country
• Sites: 1

Brief 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). 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.

Conditions

Depression in Adolescence

Keywords

depression; adolescence

Outcome Measures

Primary Outcomes (3)

• Children's Depressing Rating Scale-Revised

  Clinician-administered assessment of depression severity (dimensional) assessment of depression Clinician-administered assessment of depression severity (dimensional)

  baseline and 12-week follow-up

• Reynolds Adolescent Depression Scale-2 (RADS-2)

  Self-report measure of depression severity (dimensional)

  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

  baseline and 12-week follow-up

Secondary Outcomes (2)

• Patient Health Questionnaire-9

  baseline and 12-week follow-up

• Mood Ratings on the Trier Social Stress Test

  Acute (baseline and throughout study procedures)

Other Outcomes (10)

• Generalized Anxiety Disorder-7

  baseline and 12-week follow-up

• Multidimensional Anxiety Scale for Children-2 (MASC-2)

  baseline and 12-week follow-up

• Glutamate

  Acute (baseline and 90 min. follow-up)

Study Arms (1)

Study Participants

All depressed participants will undergo the same study procedures

Behavioral: Trier Social Stress Test (TSST)

Interventions

Trier Social Stress Test (TSST) BEHAVIORAL

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 Participants

Eligibility Criteria

• Age: 14 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Adolescents presenting to school counseling centers, community clinics, and/or medical centers (primary care, psychiatry, etc)

You may qualify if:

• DSM-V criteria for a depressive disorder
• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, Los Angeles: lead
• University of Southern California: collaborator
• University of California, Irvine: collaborator
• Columbia University: collaborator
• Mayo Clinic: collaborator
• University of California, San Francisco: collaborator

Study Sites (1)

University of California, Los Angeles

Los Angeles, California, 90095, United States

RECRUITING

Related Publications (1)

• 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.

  PMID: 38235411 DERIVED

MeSH Terms

Conditions

Depression

Interventions

Psychological Tests

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Behavioral Disciplines and Activities

Study Officials

• Tiffany Ho, Ph.D.

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tiffany Ho, Ph.D.

CONTACT

310-825-2961; tiffany.ho@psych.ucla.edu

Cheryl Sun, B.A.

CONTACT

cherylsun@psych.ucla.edu

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 8, 2022
• First Posted: April 15, 2022
• Study Start: July 6, 2023
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 30, 2028
• Last Updated: May 28, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share

Locations

US (1)