Characterization and Treatment of Adolescent Depression

Depression Clinical Trial

Official title: Characterization and Treatment of Adolescent Depression

Status Recruiting

Clinical Trial Summary

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. - Visits may include paper-and-pencil and computer tests of mood, memory, and thinking; specialized computer games; and structural and brain imaging. If eligible, study participants may return several times a year for up to two years. This part of the study does not involve treatment. - Participants may be eligible for outpatient treatment for up to 25 weeks. This includes evidenced-based "talk" therapy. Participants may choose either Interpersonal Psychotherapy for Adolescents (IPT-A) or Cognitive Behavioral Therapy (CBT). If indicated, participants may opt to receive standard medication treatments along with psychotherapy. Research includes computer tasks and brain imaging. 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.

Clinical Trial 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 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 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. 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 outpatient clinical care in the form of open-label Interpersonal Psychotherapy for Adolescents (IPT-A, Mufson et al up to 26 weeks), Cognitive Behavioral Therapy (CBT; up to 26 weeks), or the Unified Protocols for Adolescents (UP-A) (Ehrenreich-May et al. 2018; for up to 26 weeks). The patient and families can choose which form of psychotherapy they prefer. Those who are on medication when they enroll will be able to continue their medications. Those who do not improve with psychotherapy, will be offered medication plus psychotherapy for up to 12 weeks. Furthermore, for those who are on medication when they enroll and do not improve when psychotherapy is added, we will offer to change the dose or provide a trial of a different drug than the one they have been receiving. 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 or be offered participation in other IRP depression protocols, as appropriate. 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, PROMIS-A-SR, PROMIS-A-PR 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: Questionnaires: MFQ, ARI, SCARED, PROMIS-A-SR, PROMIS-A-PR Secondary outcomes: Questionnaires: Family-function measures (FAD, FBS, and FRFC-P), quality of life measure (PQ-LES-Q), sleep measures (PROMIS-Sleep) Behavioral task: Five Minute Speech Sample, Parent-Child Discussion Task, SMT, Mood Induction task, Parent-Child Discussion Task (PCDT) ;

Related Conditions & MeSH terms

• Depression
• Depressive Disorder

• NCT number: NCT03388606
• Study type: Observational
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Daniel S Pine, M.D.
• Phone: (301) 594-1318
• Email: daniel.pine@nih.gov
• Status: Recruiting
• Start date: December 28, 2017
• Completion date: July 1, 2025