An observational study in Depression, sponsored by National Institute of Mental Health (NIMH). Recruiting at 3 sites in United States. Open to participants aged 11 Years to 25 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-10-26.
Sponsored by National Institute of Mental Health (NIMH) · Observational
This research study seeks to find causes and treatments of depression in teenagers. The study goals are to increase our knowledge of treatments for depression and understand how the brain changes when teenagers have depression. The study will also compare teenagers with depression to those without mental health diagnoses.
This outpatient study is recruiting participants ages 11-17 who are depressed. They must have a pediatrician or other medical provider, be medically healthy, and able to perform research tasks. They may not currently be hospitalized, psychotic or actively suicidal. Teenagers with depression are eligible even if they are taking medication.
The study begins with an evaluation that includes clinical assessment, interviews, and questionnaires.
All clinical evaluations, research tasks and visits are free of cost. Participants are compensated for research activities. Parents and teenager must agree to the teenager s participation in research.
The study is conducted at the NIH in Bethesda, Maryland and enrolls participants from the Washington DC Metro region within 50 miles of NIH. Transportation expenses are reimbursed by NIMH.
Objective
Depression has a prevalence of 19% in the US population and close to 350 million people suffer from the disorder worldwide. The chronic course of depression and its early onset - a maximal incidence in adolescence and young adulthood - contribute to it being a leading cause of disability worldwide. Yet, compared to many other medical conditions, we know little about the mechanisms underlying depression. In recent years, reward processing has been proposed to underlie several key behavioral and neural aberrations observed in depression. This has led to the promise that targeting reward processing may lead to much needed breakthroughs in the field. In this protocol we seek to characterize and treat depression in youth by integrating methodological and conceptual approaches that specifically focus on reward processing. Patients and their families can elect to participate in standard outpatient clinical care in this protocol. Our objective is to answer four key questions:
What is the concordance of measures of reward processing in depression over time?
Measurement is fundamental to answering substantive questions in science. Our review of the literature identified gaps in the reliability of reward measurement, the concordance between measures, and a dearth of studies that employ repeated-measure designs. We propose to tackle this using a multi-method approach in a longitudinal design.
Studies from our own group demonstrate that stress in early life has an impact on how rewards and punishers are processed in the brain several years later. Similarly, there is good evidence for the acute effects of stress on reward processing, as indicated in our recent metanalysis. And, of course, there is ample evidence for the role on how stressful events worsen symptoms of depression. The current protocol will utilize the Trier Social Stress Test, one of the best established paradigms for examining the acute impact of stress on people, to examine associations among stress responsitivity, reward function, and psychopathology. We also wish to explore more deeply the role of family environment on stress in teens with major depression. There is a substantial literature on the role of family environment in moderating or exacerbating stress in teens, and measures and methods to assess this would be important to understand its role in teen depression.
Study population
We will study three populations: (1) Healthy volunteer children and adults (HVs; n=600); (2) Participants with Major Depressive Disorder (MDD; n=500); (3) parents (biological or legal guardians) of children with MDD or HVs who are enrolled in this protocol (N=800 total as 400/200/200 respectively). Study participants will be aged 11-17 years at initial enrollment in Characterization; this is a longitudinal study and participants who turn 18 may continue in it for up to two years. Previously we enrolled 4 cohorts. Youths with Subthreshold Depression (s-MDD) (n=200 were to be enrolled; we have enrolled n=8 over the life of the protocol and no subjects with s-MDD have been enrolled after Dec 2021)
Design
This is a Characterization study that, as of 2022, includes longitudinal observation of two adolescent cohorts. HV and MDD subjects will take part in a longitudinal, observational study that involves clinical assessment, computer tasks, fMRI and MEG scanning and continue to return for up to two years. A sample of young adult HVs (18-30 years old) will also be enrolled as a comparison cohort. Those previously enrolled as subthreshold MDD (s-MDD) will be followed for up to two years (from their initial enrollment); with Amendment J, we ceased enrolling this population; no new participants with s-MDD have been enrolled since Dec, 2021. Adolescent patients who still suffer from current MDD will be offered standard outpatient care with clinically indicated treatments. During and following outpatient clinical care, participants with MDD will continue in Characterization.
Outcome measures
For Objective 1
Primary Outcomes
fMRI: Carnival Task, AX-CPT Task; Flanker Task; Mood Induction Task
AX-CPT Task, Flanker Task
For Objective 2
Primary outcomes
fMRI: Carnival Task, AX-CPT Task; Flanker Task; Mood Induction Task
Questionnaires: MFQ, ARI, SCARED, PROMIS-A-SR, PROMIS-A-PR
For Objective 3
Primary outcomes: Carnival Task, AX-CPT Task; Flanker Task; Mood Induction Task
Questionnaires: SCSC, MFQ
fMRI/MEG: Activity in prefrontal cortex and striatum in response to rewards and to events engaging cognitive control
For Objective 4
Primary outcomes: Carnival Task, AX-CPT Task; Flanker Task; Mood Induction Task
Questionnaires: MFQ, ARI, SCARED, PROMIS-A-SR, PROMIS-A-PR
Questionnaires: Family-function measures (FAD), quality of life measure (PQ-LES-Q)
Behavioral task: Five Minute Speech Sample, Parent-Child Discussion Task, SMT, Mood Induction task, Parent-Child Discussion Task (PCDT)
8,577 studies on the registry are indexed under Depression; 1,720 are open to participants now.
This study's planned enrollment of 4,100 is above the median of 175 across 1,257 observational studies indexed under Depression.
Browse Depression studies →National Institute of Mental Health (NIMH) is the lead sponsor of 367 studies on the registry; 45 are open to participants now.
Of its 25 completed or terminated interventional studies of FDA-regulated products, 24 (96%) have results posted.
Counted across the registry records on this site, refreshed daily.
A clinical population of depressed adolescents age 11-17 (inclusive)@@@
Inclusion criteria for Youth with MDD (all must be met):
Five or more of the following symptoms have been present during the same 2-week period and represent a change from previous functioning; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure.
INCLUSION CRITERIA FOR HEALTHY VOLUNTEERS:
Adolescent Healthy Volunteers (Group 3a)
Adult Healthy Volunteers (Group 3b)
INCLUSION CRITERIA FOR PARENTS OF ENROLLED YOUTH (Group 4):
EXCLUSION CRITERIA: (All patients)
-Exclusion Criteria for MDD patients (Group 1)
Youths with passive suicidal ideation and/or past active suicidal ideation are still eligible.
Participants with repeated self-harm occurring in the context of inter-personal conflict.
-Exclusion criteria for youths meeting modified DSM criteria for Subthreshold Depression (Group 2) (this cohort is historical only; previously n=200 to be enrolled; ceased enrolling this population with Amendment J (2022); none enrolled after Dec 2021):
NIMH IRP Employees/staff and immediate family members will be excluded from the study per NIMH policy.
-Healthy volunteer youths and adults exclusion criteria:
Parents of enrolled participants (group 3) exclusion criteria:
--Parents who are unable to understand or read English well enough to complete the study interview and tests.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
DSM diagnostic criteria
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Adolescents with a current or past history of meeting full critieria for major depressive disorder
Behavioral: Growth Mindset
Adolescents with no history of significant psychiatric or medical disorders (as defined in the protocol) currently or in the past.
biological parent or legal guardian of an enrolled adolescent (who is a healthy volunteer, has s MDD \[subthreshold depression\], or has MDD \[Major Depressive Disorder\]) participant
30 Minute interactive video
Mood and Feelings Questionnaire
changes in MFQ scores over time
Time frame: ongoing
Not enrolling at this site.
Not enrolling at this site.
Plan to share: No
Started Dec 2017 (actual). Primary completion is estimated for Jul 2027, 114 months after the start.
Of 460 non-industry observational studies under Depression, half reached primary completion within 34 months of starting (the median), counting those still running; a quarter within 14 and three quarters within 63. This study's planned 114 months is above that.
Counting every sponsor, half of 493 studies reached it within 33 months; a quarter within 13 and three quarters within 62.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
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