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.
All sexes and genders
All ethnicities
Ages 14-21
Postpubertal (Tanner stage > 3)
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
Adolescents presenting to school counseling centers, community clinics, and/or medical centers (primary care, psychiatry, etc)
Case-only
Prospective
Trier Social Stress Test (TSST)
BehavioralIn 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.
Children's Depressing Rating Scale-Revised
Clinician-administered assessment of depression severity (dimensional) assessment of depression Clinician-administered assessment of depression severity (dimensional)
Reynolds Adolescent Depression Scale-2 (RADS-2)
Self-report measure of depression severity (dimensional)
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
Patient Health Questionnaire-9
Self-report measure of depression severity (dimensional) used for adults (which will facilitate cross-study comparisons)
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 \[a bit\]
Generalized Anxiety Disorder-7
Self-report measure of anxiety severity (dimensional) used for adults (which will facilitate cross-study comparisons)
Multidimensional Anxiety Scale for Children-2 (MASC-2)
Self-report measure of anxiety severity (dimensional)
Glutamate
Change in glutamate (institutional units) in corticolimbic regions following TSST
Glutamate
Change in glutamate (institutional units) in corticolimbic regions after SSRI treatment
Click on the lead sponsor to view all of their trials.
University of California, Los Angeles
Lead sponsor
University of Southern California
Collaborator
University of California, Irvine
Collaborator
Columbia University
Collaborator
Mayo Clinic
Collaborator
University of California, San Francisco
Collaborator
National Institute of Mental Health (NIMH)
Collaborator
