Characterization and Treatment of Adolescent Depression

  • STATUS
    Recruiting
  • End date
    Jul 1, 2025
  • participants needed
    4100
  • sponsor
    National Institute of Mental Health (NIMH)
Updated on 25 May 2022
depressive disorder
depressed mood
suicide
suicidal
insomnia
major depressive disorder
Accepts healthy volunteers

Summary

Background

Almost 20% of Americans have depression. It is a leading cause of disability because it is chronic and it starts early. The highest incidence is among adolescents and young adults. But researchers don t know much about why some people become depressed whilst others don t. One possibility is that the way people process rewarding stimuli could be related to their risk for depression.

Objective

To characterize and treat depression in youth by focusing on reward processing.

Eligibility

People ages 11 17 with major depressive disorder or subthreshold depression

Healthy volunteers ages 11 17

Design

Participants will be screened with interviews and questionnaires. They will have memory, thinking, and concentration tests. They may have a urine pregnancy test or have photos or videos taken.

At the initial visit, participants will:

Perform tasks and be interviewed

Have functional magnetic resonance imaging (MRI) scans. For this, participants will lie in a metal cylinder in a magnetic field. They will do study tasks while looking at a screen in the scanner.

Look at pictures of stimuli that signal win (rewards) or loss and get money for making certain choices.

Have brain and eye activity monitored

Do tasks in a virtual reality environment

Wear an activity monitor

Choose to have blood taken for research studies

Perform tasks while in magneto-encephalography a machine that uses sensitive magnetic sensors to measure the brain s electric activity

Participants will get phone prompts at home to ask about their mood.

Participants will have several follow-up visits the first year, then 1-2 each year until they are 25. They will repeat some tasks above.

Some participants with depression can elect to receive outpatient treatment at NIH and can receive inpatient treatment at NIH, if they wish. None of the treatments are experimental, that is, all treatments are standard and have an evidence base. Patients will have more visits before and after they have treatment. They will do some of the tests above plus drug testing. Participants who are in treatment and their parents will talk with a Senior Attending physician, a nurse, social worker, or psychologist. Those in outpatient treatment will have practice work between visits. Those who are inpatients will have practice work during their inpatient treatment and adjustments to medication can be made.

Description

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 or inpatient clinical care in this protocol. Our objective is to answer four key questions:

  1. 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.
  2. Are reward processing aberrations in depression similar to those in other common problems of childhood, such as anxiety and irritability? Specificity-in this case establishing which reward aberrations are unique to a certain phenotype as opposed to a generic finding related to psychopathology-is important for both nosology (disease classification) and for designing rational treatments for psychiatric problems. Below, we describe how we propose to answer this question by characterizing reward processing in those with depression and comparing it to processing in those with other common psychiatric problems in youth, such as anxiety and irritability.
  3. How does reward processing interact with systems subserving sense of agency? As described above, decision-making is an intricate part of reward processing. It is assumed that higher-order cognitive processes, such as the sense of ownership of one s actions-referred to as sense of agency-influence reward processing. Establishing the role of such higher-order processes in depression could lead to developing treatments that boost cognition and restore reward processing in depression. Below, we propose to answer this question by testing whether inter-individual differences in sense of agency explain variation in depression via reward processing (a mediation model).
  4. How is reward processing affected by changes in metabolic, inflammatory, and neuroendocrinological markers?

There is mounting evidence for differences in metabolic, inflammatory, and neuroendocrine markers when comparing those with and without MDD; however, the relationship of such differences to reward processing-the focus of this protocol-remain poorly examined. We wish to explore the direction of effect between inflammatory responses and metabolic changes with depression and reward processes. We wish to do this informed by knowledge of an individual s genetic background. The aim is to establish trajectories of stability/change in metabolic and inflammatory markers and relate them to mood changes and reward changes over time. We also wish to align our protocol with Dr Zarate s Protocol 17-M-0060, Neuropharmacologic Imaging and Biomarker Assessments of Response to Acute and Repeated-Dosed Ketamine Infusions in Major Depressive Disorder that focuses on depression in adults. Collecting these data on adolescents will allow us to identify differences and overlaps between adolescents (from this protocol) and the adults in Dr. Zarate s protocol 17-M-0060.

5. How is reward processing affected by environmentally-generated stress?

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 emergence of the COVID-19 pandemic presents an unprecedented challenge for the world s physical health, but is also expected to have a profound impact on people s psychological wellbeing. The COVID-19 pandemic is a huge medical challenge to be sure, and, by virtue of being a naturally occurring stress, presents an opportunity for us, using longitudinal methods, to learn more about how humans respond to such environmental influences. Moreover, it offers an opportunity for us to understand more about human behaviour and potentially use such knowledge to inform future interventions. The aim, using remote on-line methods, is to learn about how such environmental stress is experienced by healthy volunteer teens and those with depression, the relationship between stress and self-rated measures of depression, and the association of measures of stress and depression on reward processing.

Study population

We will study four populations: (1) Healthy volunteer children and adults (HVs; n=600); (2) Participants with Major Depressive Disorder (MDD; n=500); (3) Participants with subthreshold depression (s-MDD; n=200); (4) parents (biological or legal guardians) of children with MDD, s-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 the time of screening and initial enrollment in Characterization; this is a longitudinal study and participants who turn 18 may continue in it until they are 25.

Design

This is a Characterization study that includes longitudinal observation of three adolescent cohorts.. HV, s-MDD and MDD subjects will take part in a longitudinal, observational study that involves clinical assessment, computer tasks, blood for inflammatory and neuroendocrinological markers, fMRI and MEG scanning and continue to return until they reach 25 years of age. A sample of young adult HVs (18-30 years old) will also be enrolled as a comparison cohort.

Adolescent patients who still suffer from MDD will be offered outpatient clinical care in the form of open-label Cognitive Behavioral Therapy (CBT; up to 26 weeks). During and following outpatient clinical care, participants with MDD will continue in Characterization. Upon completion of clinical care patients will return to care in the community.

MDD patients who are clinically unstable and are eligible for standard clinical treatment as inpatients or day-patients may enter treatment at NIH. They may do this after starting in Characterization or at their initial enrollment.

Outcome measures

For Objective 1

Primary Outcomes

fMRI: Monetary incentive delay task

Magnetoencephalography: Monetary incentive delay task

Automated Affect encoding: variables obtained through machine learning analysis

For Objective 2

Primary outcomes:

fMRI: Monetary Incentive Delay Task

Questionnaires: MFQ, ARI, SCARED

For Objective 3

Primary outcomes:

Questionnaires: PCSC, SCSC, MFQ

Imaging (fMRI): Activity in prefrontal cortex and striatum in response to controllable setback cues in the Persistence after Setbacks task

For Objective 4

Primary outcomes:

Inflammatory and metabolic markers in blood

fMRI: Monetary Incentive Delay Task

Questionnaires: MFQ, ARI, SCARED

For Objective 5

Pirmary outcomes:

Questionnaires: MFQ, ARI-self, SCARED, COVID-19 Questionnaire,

Behavioral task: SMT

Details
Condition Depression
Treatment Growth Mindset, Comparison Session
Clinical Study IdentifierNCT03388606
SponsorNational Institute of Mental Health (NIMH)
Last Modified on25 May 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Youths who meet DSM 5 criteria for Major Depressive Disorder (Group 1)
Inclusion criteria for Youth with MDD (all must be met)
Ages 11-17 at the time of enrollment in Characterization
Current diagnosis of DSM-5 Major Depressive Disorder (within the last six months from assessment) which are
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
Depressed mood most of the day, nearly every day, as indicated by either subjective report (e.g., feeling sad, blue, "down in the dumps,"or empty) or observation made by others (e.g., appears tearful or about to cry). (In children and adolescents, this may present as an irritable or cranky, rather than sad, mood.)
Markedly diminished interest or pleasure in all, or almost all, activities every day, such as no interest in hobbies, sports, or other things the person used to enjoy doing
Significant weight loss when not dieting or weight gain (e.g., a change of more than 5 percent of body weight in a month), or decrease or increase in appetite nearly every day
Insomnia (inability to get to sleep or difficulty staying asleep) or hypersomnia (sleeping too much) nearly every day
Psychomotor agitation (e.g., restlessness, inability to sit still, pacing, pulling at clothes or clothes) or retardation (e.g., slowed speech, movements, quiet talking) nearly every day
Fatigue, tiredness, or loss of energy nearly every day (e.g., even the smallest tasks, like dressing or washing, seem difficult to do and take longer than usual)
Feelings of worthlessness or excessive or inappropriate guilt nearly every day (e.g., ruminating over minor past failings)
Diminished ability to think or concentrate, or indecisiveness, nearly every day (e.g. appears easily distracted, complains of memory difficulties)
Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideas without a specific plan, or a suicide attempt or a specific plan for committing suicide
Symptoms cause clinically significant distress or impairment in social
The episode is not attributable to the physiological effects of a substance or to another medical condition
occupational/academic, or other important areas of functioning
Is failing his/her treatment as defined as a current CGAS score less than or equal to 60
Added criteria for Children with MDD entering inpatient treatment. In addition to
If the child has a psychiatrist, the child s psychiatrist or treater agrees that the child s response to his/her current treatment makes it clinically appropriate to change the child s current treatment
criteria above, the youth
On the basis of record review and interviews with child and parent, the research team agrees that the child s response to his/her current treatment is no more than minimal
\---Meets criteria for on-going MDD
Youths who meet modified DSM criteria for Subthreshold Depression (Group 2)
Added criteria for Children with MDD entering outpatient treatment. In addition to
Inclusion criteria for subthreshold depressive disorder are
criteria in above, the youth
Ages 11-17 at the time of enrollment in Characterization
An episode of depressed mood or loss of interest or pleasure lasting at least 1 week plus
At least two of the seven other DSM-5-associated symptoms for major depression
Occurring in the last six months
INCLUSION FOR HEALTHY VOLUNTEERS
Adolescent Healthy Volunteers (Group 3a)
Youth 11 to 17 years of age at time of enrollment in Characterization
The adolescent must be competent to assent; parents must be able comprehend and provide permission for their child (consent)
Participants will be willing to participate in NIMH IRB approved research protocols. Minors will be asked to sign assent forms and their parents will sign the consent form
Participants will be willing to undergo an evaluation which may include a psychiatric interview, review of medical history (including Tanner staging for minors), and pregnancy testing
Speaks English
Have an identified primary care clinician
Adult Healthy Volunteers (Group 3b)
Adults 18 to 30 years of age at time of enrollment in Characterization
Subjects must be competent to consent
Participants will be willing to participate in NIMH IRB approved research protocols
Participants will be willing to undergo an evaluation, which may include a psychiatric interview, review of medical history, and pregnancy testing (for females)
Speaks English
Has an identified primary care clinician
INCLUSION CRITERIA FOR PARENTS OF ENROLLED YOUTH (Group 4)
Are the biological parent or legal guardian of an enrolled adolescent (who is a healthy volunteer, has s-MDD, or has MDD) participant
Those of all ages are eligible if they are a parent of a currently enrolled participant

Exclusion Criteria

(All patients)
Exclusion Criteria for MDD patients (Group 1)
Meets criteria for schizophrenia, schizophreniform disorder, schizoaffective illness, bipolar disorder, more than mild Autism Spectrum Disorder, Anorexia Nervosa or other severe Eating Disorder
Intellectual disability (clinically identified or IQ less than 70)
For subjects with major depression or sub-threshold major depressive episode: Symptoms of depression are due to the direct physiological effects of a drug of abuse, or to a general medical or neurological condition by self and parent report
Currently pregnant or lactating by self and parent report and urine pregnancy test
Meets DSM-5 criteria for alcohol or substance use disorder (excluding tobacco and nicotine use) within the last three months. This is determined solely by clinical interview of child and parent (e.g. KSADS)
Current active suicidal ideation (i.e., presence of intent for engaging in suicidal behaviors)
Youths with passive suicidal ideation and/or past active suicidal ideation are still
eligible
Intellectual disability (clinically identified or IQ less than 70)
Participants with repeated self-harm occurring in the context of inter-personal
conflict
NIMH IRP Employees/staff and immediate family members will be excluded from the study
per NIMH policy
Exclusion criteria for youths meeting modified DSM criteria for Subthreshold
Healthy volunteer youths and/adults exclusion criteria
Depression (Group 2)
Intellectual disability (clinically identified or IQ less than 70)
Any serious medical condition (such as epilepsy, heart disease requiring medication)
by self and parent report
Meets criteria for subthreshold depression (as defined above)
Past or current diagnosis of a manic or hypomanic episode, major depression)
schizophrenia, schizophreniform disorder, schizoaffective illness, Tourette Disorder
or Autism Spectrum Disorder, Anorexia Nervosa or other severe Eating Disorder
Parents of enrolled participants exclusion criteria
Meets DSM-5 criteria for alcohol or substance abuse within the last three months by
self and parent report
NIMH IRP Employees/staff and immediate family members will be excluded from the study
per NIMH policy
Any serious medical condition (such as epilepsy, heart disease requiring medication)
by self and parent report
Past or current diagnosis of any mood disorder (manic or hypomanic episode, major
depression), anxiety disorder (except specific phobia), Obsessive Compulsive Disorder
(OCD), Post-Traumatic Stress Disorders (PTSD), Conduct Disorder, schizophrenia
schizophreniform disorder, schizoaffective illness, Tourette Disorder, or Autism
Spectrum Disorder
Meets DSM-5 criteria for alcohol or substance abuse within the last three months by
self and parent report; for adults, past history of substance dependency or substance
abuse within the last three months by self-report
NIMH IRP Employees/staff and immediate family members will be excluded from the study
per NIMH policy
Parents who are unable to understand or read English well enough to complete the study
interview and tests
Parents who are a current NIMH employee, or staff member, or a family member of an
NIMH employee. NIMH IRP Employees/staff and immediate family members will be excluded
from the study per NIMH policy
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

0/250

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note