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NCT number NCT03388606
Study type Interventional
Source National Institutes of Health Clinical Center (CC)
Contact Argyris Stringaris, M.D.
Phone (301) 928-8941
Email argyris.stringaris@nih.gov
Status Recruiting
Phase Phase 2
Start date December 28, 2017
Completion date August 20, 2020

Clinical Trial 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 how depression occurs. It may be linked to reward processing.

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:

- Repeat screening tests

- Watch an interactive video about mood problems and anxiety

- Have functional MRI. Participants will lie in a metal cylinder in a magnetic field. They will do study tasks on a screen.

- Look at pictures to evoke happiness, sadness, or fear and get money for making certain choices. Parents can check the pictures before the children see them.

- Have brain and eye activity monitored

- Do tasks in a virtual reality environment

- Wear an activity monitor

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

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

Some participants with depression will have more visits before and after they have treatment. They will do some of the tests above plus drug testing. Participants and their parents will talk with a nurse, social worker, or psychologist. They will have practice work between visits.


Clinical Trial Description

OBJECTIVE:

Depression has a prevalence of 19% in the US population (Kessler & Bromet, 2013) and close to 350 million people suffer from the disorder worldwide (WHO, 2012). 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 (WHO, 2014). Yet, compared to many other medical conditions, we know little about the mechanisms underlying depression. In recent years, reward processing have 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. 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 esigning 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. Do Growth Mindset Interventions (GMI) impact on reward processing to influence depression?

Treatments of depression in youth have stalled and are on the whole still unsatisfactory. GMI have emerged as a concise, circumscribed means to influence perceived control and have an evidence base for improving emotional problems in youth. Here, we conduct a randomized Controlled Trial of a very concise GMI to examine whether GMI impacts on agency, reward and depression.

STUDY POPULATION:

We will study three populations: (1) Healthy volunteers (HVs; n=300); (2) Participants with Major Depressive Disorder

(MDD; n=300); (3) Participants with subthreshold depression (s-MDD; n=200). Study participants will be aged 11-17 years.

DESIGN:

The study has two parts. The first part is Characterization, where HV, s-MDD and MDD subjects will be take part in a longitudinal, observational study that involves clinical assessment, computer tasks and fMRI and MEG scanning and continues up to age 25 years. The second part is Intervention, that has two components: a) GMI RCT, where participants will be invited to participate in a 30-minute, single-session RCT comparing GMI to a control session. This component, including assessment pre- and post- single-session-RCT, lasts for 2-5 weeks; b) CBT treatment, where upon completing the GMI RCT, patients who still suffer from MDD will be offered open-label Cognitive Behavioral Therapy (CBT; up to 25 weeks or a total of 50 sessions). During and following completion of the RCT and/or CBT, participants with MDD will continue in Characterization. Upon completion of CBT 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 and may enter treatment at NIH after having started in Characterization or at the time of 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 Outcome: MFQ


Study Design


Related Conditions & MeSH terms


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