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Inflammatory and Glutamatergic Mechanisms of Sustained Threat in Adolescents With Depression

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…

ClinicalTrials.gov IDNCT05329441

PhaseNot Applicable

Enrollment160

SponsorUniversity of California, Los Angeles

Age14 Years

SexALL

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Conditions studied

Depression in Adolescence

About this study

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 outcomes

Children's Depressing Rating Scale-Revised (baseline and 12-week follow-up)
Reynolds Adolescent Depression Scale-2 (RADS-2) (baseline and 12-week follow-up)
Kiddie Schedule for Affective Disorders and Schizophrenia (KSADS-PL) (baseline and 12-week follow-up)

Eligibility information

Inclusion Criteria: * 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) 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

Study locations

University of California, Los Angeles, Los Angeles, California 90095 United States

Before you participate: Varda Clinical is an independent discovery tool, not the study sponsor or a medical provider. Eligibility can only be determined by the official study team. Discuss potential risks and benefits with a qualified healthcare professional.

Source: ClinicalTrials.gov. Record last refreshed by Varda Clinical: 2026-09-27.