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Depression

Teen Depression Study: Understanding Depression in Teenagers
Join a Research Study: Enrolling nationally from around the country

Depression is a serious medical illness; it’s not something that you have made up in your head. It’s more than just feeling “down in the dumps” or “blue” for a few days. It’s feeling “down” and “low” and “hopeless” for weeks at a time. Learn more about depression.

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Featured Studies

Featured studies include only those currently recruiting participants. Studies with the most recent start date appear first.

Reward Function and Therapy for Late-Life Depression

Study Type: Interventional
Start Date: December 31, 2018
Location: White Plains, New York
Eligibility: Ages 60 and Older, Does Not Accept Healthy Volunteers

The goal of this study is to learn about changes in the brain that occur during Engage, a psychotherapy for depression in older adults, and how they may differ from changes that occur during supportive therapy. Older adults with depression will receive 9 weeks of either Engage or supportive therapy and will complete research assessments before the therapy begins and at weeks 3, 6, and 9 of treatment. Research assessments will include questionnaires, computer tasks, and recordings of electrical brain activity (also called electroencephalography or EEG).

Procedures for Sample Acquisition and Distribution for The Human Brain Collection Core

Study Type: Observational
Start Date: December 14, 2018
Location: Bethesda, Maryland
Eligibility: Ages N/A–120, Does Not Accept Healthy Volunteers

Background:

The Human Brain Collection Core (HBCC) collects brain and other tissues. They get these from deceased people who may or may not have had psychiatric disorders. The next of kin gives permission for researchers to get the tissues. Researchers want to collect medical details of people whose brains are donated. They also want to use the donated tissue to study brain chemistry and structure. This could lead to better treatments for mental illness.

Objective:

To create a collection of human brain tissue to learn about the causes and mechanisms of mental disorders.

Eligibility:

People willing to donate their deceased relative s brain tissue. The deceased person could not have had any of the following:

Severe mental retardation

Long-lasting seizure disorder

Infections that affect the brain

Decomposition

Brain damage

Being on a respirator for more than 12 hours

Major sepsis

Serious renal or hepatic disease

Certain dementias and degenerative diseases

Design:

Medical Examiner s Offices will screen donors who have recently died. Some others will be screened by hospitals or funeral homes.

Participants will be the next of kin. They will give consent for HBCC to obtain brain tissue from the deceased person. The tissue will be frozen for future research.

Participants will have a 30-minute phone call. They will answer questions about the deceased person s medical and psychiatric conditions. They will answer questions about the person s use of medicines and drugs.

Participants will be contacted by a social worker. They will be asked for permission to access the deceased person s medical records.

Effects of an ER Beta Agonist (Lilly Compound LY500307) on Estradiol-Withdrawal-Induced Mood Symptoms in Women With Past Perimenopausal Depression

Study Type: Interventional
Start Date: December 14, 2018
Location: Bethesda, Maryland
Eligibility: Females, Ages 45–65, Does Not Accept Healthy Volunteers

Background:

Some women who had depression in the perimenopause may have mood symptoms again if they stop estrogen therapy. Estrogen acts in the brain and other tissues by binding to at least three types of estrogen receptors. One of these receptors, estrogen receptor beta may affect anxiety and depression. The drug LY500307 acts only on this receptor. In this study, researchers will initially give you estrogen and then suddenly stop estrogen after three weeks. Then they will study how LY500307 affects mood symptoms.

Objectives:

To study how withdrawing estradiol affects mood. To test the safety and side effects of LY500307.

Eligibility:

Healthy women ages 45-65 who had depression related to perimenopause in recent years and whose mood systems got better with estradiol

Design:

-Participants will be screened with:

Medical history

Physical exam

Blood tests

Psychiatric interview

Gynecological exam

- Participants able to get pregnant must use effective barrier birth control throughout the study.

- During the first 3 weeks, participants will wear an estrogen patch. It is 1x2 inches and will be replaced every 3 days.

- For the next 3 weeks, participants will take 3 study capsules every morning. They will not know if they get the study drug or placebo.

- Some participants will also take a progesterone-like drug for 1 week at the end of the medication phase of the study.

- Participants will have 9 one-hour study visits. They will have blood samples and vital signs taken. They will answer questions about mood and behavior symptoms.

- Participants will keep a daily log of these symptoms.

- Participants will have 2 transvaginal ultrasounds. A probe is temporarily placed 2-3 inches into the vaginal canal and sound waves are used to create pictures of the lining of the uturus.

- Participants will have a final visit 4 weeks after stopping the study drug. They will answer questions about mood and side effects.

EEG Synchronized TMS Trial for Depression

Study Type: Interventional
Start Date: November 30, 2018
Location: Charleston, South Carolina
Eligibility: Ages 21–70, Does Not Accept Healthy Volunteers

Daily prefrontal TMS for depression, as developed by the PI, involves delivering TMS pulses to the prefrontal cortex and not assessing what the actual EEG phase is of the person's brain. In cardiology, in order to stimulate the heart effectively, one has to know the rhythm and phase of the heartbeat in order to perform cardioversion. The investigators wonder if it is important to time the brain stimulation with the phase of the person's brain. The brain has definite rhythms, and cycles through being excited or resting. A common EEG rhythm is alpha frequency. Theoretically, the effect of the TMS pulse might be diminished if it was delivered when the brain was temporarily cycling into an off state.

In the r21 part of this grant, the investigators designed and constructed a combined TMS/EEG/fMRI system. With that equipment the investigators found that TMS pulses have different effects deeper in the brain as a function of the EEG alpha phase. Pulses delivered during a rising phase produce larger blood flow changes deeper in the brain than do pulses delivered during a falling phase.

In the R33 phase of the grant the investigators now take that idea into a small clinical trial in depression to test if synchronized pulses have a larger clinical effect than do non-synchronized pulses.

Biomarkers in Repetitive Transcranial Magnetic Stimulation (rTMS) for Adolescent Depression

Study Type: Interventional
Start Date: September 24, 2018
Location: Rochester, Minnesota
Eligibility: Ages 12–18, Does Not Accept Healthy Volunteers

The Researchers are going to gather information regarding the use of rTMS as a treatment for depression in adolescents with Major Depressive Disorder. The researchers also hope to learn if measures of brain activity (cortical excitability and inhibition) collected with transcranial magnetic stimulation (TMS) can be used to identify which patients will benefit from certain types of rTMS treatment.

Leucine for Depression Study (L-DEP)

Study Type: Interventional
Start Date: September 1, 2018
Location: Los Angeles, California
Eligibility: Ages 18–65, Accepts Healthy Volunteers

Depression is very common and poses a huge disease burden. About 20% of the US population suffers from depression at lease once in their lifetime. Inflammations that are hidden inside our body as a result of aging, obesity, chronic diseases, or certain treatments (e.g., interferon for hepatitis C) appear to cause depressive symptoms and even clinical depression. Individuals with such inflammations are more likely to suffer from depression and are less likely to respond to currently available antidepressant medications. This study will test leucine, an amino acid, as a new way to mitigate depressive symptoms in response to such inflammations. This study begins with a 90-minute screening session to determine whether participants are eligible to join the main study. Those who meet the eligibility criteria will then join the main study, which will consist of taking leucine or maltodextrin (i.e., oral placebo) for 2 weeks at home and an 8-hour session at the UCLA Medical Center. A brief telephone follow-up every 3 months for 2 years with questions on mood is also planned. Approximately 90 healthy adults will be recruited for participation in the study. During the course of the study, participants will take leucine or maltodextrin for 2 weeks at home and then will be injected either lipopolysaccharide (LPS) or saline (i.e., intravenous placebo) at the UCLA Medical Center. LPS is a bacterial substance that can initiate chemical reactions that are similar to those seen in individuals with mild sickness symptoms, such as a slight increase in body temperature, muscle aches, or tiredness. It is a safe way of investigating the body's response to inflammation and how these changes may alter cognitive, emotional, or neural function. It has been given thousands of times to healthy volunteers - both younger and older adults - without any serious side effects.

Confirmatory Efficacy and Safety Trial of Magnetic Seizure Therapy for Depression

Study Type: Interventional
Start Date: June 25, 2018
Locations: Dallas, Texas; Toronto, Ontario, Canada
Eligibility: Ages 18 and Older, Does Not Accept Healthy Volunteers

This trial aims to assess the efficacy and tolerability of Magnetic Seizure Therapy (MST) as an alternative to electroconvulsive therapy (ECT) for depression. Even with multiple medication trials, 30 - 40% of patients will experience a pharmacologically resistant form of illness. The ineffectiveness of current treatments for major depressive disorder (MDD) coupled with the economic burden associated with the disorder engenders a need for novel therapeutic interventions that can provide greater response and remission rates.

Concurrent fMRI-guided rTMS and Cognitive Therapy for the Treatment of Major Depressive Episodes

Study Type: Interventional
Start Date: May 17, 2018
Location: Bethesda, Maryland
Eligibility: Ages 18–65, Does Not Accept Healthy Volunteers

Background:

Repetitive transcranial magnetic stimulation (rTMS) is a treatment for depression. It stimulates the brain. Researchers want to see if using magnetic resonance imaging (MRI) scans helps locate the best area for rTMS in each person. They also want to find other ways to make it more effective.

Objective:

To study the effects of combining MRI- guided transcranial magnetic stimulation (TMS) and talk therapy on the brain in people with depression.

Eligibility:

Adults ages 18-65 with a major depressive disorder and current depression. If taking an antidepressant, should have been doing so for at least 4 weeks.

Design:

Participants will be screened with medical and psychiatric history, psychiatric evaluation, physical exam, and blood and urine tests.

Phase 1 is 1-4 visits in 1 week. Participants will have:

- Brain MRI. Participants will lie on a table in a scanner.

- Questions about their medical history and psychology symptoms

- Tests of mood and thinking

- Tests of brain activity. Participants may do tasks during these tests:

- A cone with magnetic detectors is put on the head.

- A cap with electrodes is put on the scalp.

- TMS. A brief electrical current passes through a wire coil on the scalp.

- A metal disk will be placed on the arm. A nerve will be stimulated with a small electrical shock.

Phase 2 is about 6 to 7 weeks.

- There will be 30 daily sessions of combined therapy and repetitive TMS (rTMS) for 6 weeks.

- Participants will receive rTMS and another therapy by computer.

- For rTMS, repeated pulses will pass through the coil.

- This is followed by up to 3 additional visits, when:

- Participants will repeat Phase 1 tests

- Participants will rate their depression symptoms.

Phase 3 is 3 visits over 3 months. Participants will rate their depression symptoms and repeat some of the previous questionnaires and tests of mood and thinking.

Supporting Our Valued Adolescents Pilot Randomized Controlled Trial

Study Type: Interventional
Start Date: April 17, 2018
Location: Pittsburgh, Pennsylvania
Eligibility: Ages 14–19, Does Not Accept Healthy Volunteers

The purpose of this pilot study is to provide preliminary findings testing the Supporting Our Valued Adolescents (SOVA) intervention, two social media sites (one for adolescents, one for parents) aiming to address negative health beliefs, knowledge about depression or anxiety, parent-adolescent communication, in a moderated online peer community, with the goal of increasing adolescent use of mental health services.

Ovarian Hormones and Suicide Risk

Study Type: Interventional
Start Date: April 15, 2018
Location: Chicago, Illinois
Eligibility: Females, Ages 18–45, Does Not Accept Healthy Volunteers

This within-person, crossover, 3-condition, placebo-controlled study compares the impact of three perimenstrual conditions on severity of suicidal symptoms in females with past-month suicidality but minimal risk of imminent suicide attempt. The three conditions are (1) perimenstrual withdrawal from estradiol only (during progesterone stabilization), (2) perimenstrual withdrawal from progesterone only (during estradiol stabilization), and (3) perimenstrual withdrawal from both estradiol and progesterone during placebo.

Activating and Connecting Teens (ACT) Study

Study Type: Interventional
Start Date: March 1, 2018
Location: Seattle, Washington
Eligibility: Ages 12–18, Accepts Healthy Volunteers

National data indicate over 650,000 children and adolescents are exposed to physical, sexual, or emotional abuse or physical or emotional neglect each year. Moreover, youth with a history of childhood maltreatment (CM) are at least twice as likely to develop depression and are at substantial risk for nonresponse to current best practice depression interventions (i.e., cognitive behavioral therapy and antidepressants) compared to non-maltreated peers. Research suggests that CM increases risk for depression through disruptions in the positive valence system, such as reward processing, and Behavioral Activation (BA) may be an alternative depression intervention that targets these deficits. This study takes an innovative approach integrating neural, behavioral, and novel mobile technologies to measure longitudinal change in reward processing as a mechanism of BA intervention response among depressed adolescents with a history of CM. Specifically, depressed adolescents with a history of CM will complete pre- and post- BA intervention fMRI and behavioral measures of reward processing along with daily passive mobile monitoring of physical (steps) and social (amount of texts, calls, social media usage) activity to determine 1) how BA targets neural and behavioral reward processing and real-world behavioral engagement (Specific Aim 1), and 2) whether change in neural and behavioral reward processing predicts intervention response and maintenance (Specific Aim 2).

Scaling Up Science-based Mental Health Interventions in Latin America

Study Type: Interventional
Start Date: February 13, 2018
Location: Bogotá, Colombia
Eligibility: Ages 18 and Older, Does Not Accept Healthy Volunteers

Conduct systematic, multi-site mental health implementation research in both rural and urban primary care settings with a broad group of stakeholders in the US and Latin America.

Transcranial Direct Current Stimulation in Major Depression

Study Type: Interventional
Start Date: February 2, 2018
Location: Los Angeles, California
Eligibility: Ages 18–55, Does Not Accept Healthy Volunteers

Noninvasive transcranial direct current stimulation (tDCS) is a low-intensity neuromodulation technique of minimal risk that has been used as an experimental procedure for reducing depressive symptoms and symptoms of other brain disorders. Though tDCS applied to prefrontal brain areas is shown to reduce symptoms in some people with major depressive disorder (MDD), the extent of antidepressant response often differs. Methods that map current flow directly in the brain while a person is receiving tDCS and that determine how functional neuroimaging signal changes after a series of tDCS sessions may help us understand how tDCS works, how it can be optimized, and if it can be used as an effective intervention for reducing depressive symptoms. We will investigate these questions in a two-part randomized double blind exploratory clinical trial. The first part of the trial will compare how current flow and functional imaging signal differs in the brain when using tDCS with more focal stimulation, called high definition (HD) tDCS, compared to conventional tDCS (C-tDCS) or sham (non-active) tDCS in patients with MDD.

Sixty people with depression (20 in each group) will be randomized to receive either HD-tDCS, C-tDCS or sham-tDCS for a total of 12 sessions each lasting 20 minutes occurring on consecutive weekdays. At the first and last session, subjects will receive 20-30 minutes of active or sham tDCS in the MRI scanner, which will allow us to map tDCS currents, and track changes in regional cerebral blood flow (rCBF) pre-to- post treatment using completely non-invasive methods. At the first and last session and mid-way through the trial, participants will also complete a series of clinical ratings and neurocognitive tests

EM/PROTECT: Improving Depression in Elder Mistreatment Victims

Study Type: Interventional
Start Date: January 1, 2018
Location: New York, New York
Eligibility: Ages 55–100, Does Not Accept Healthy Volunteers

The investigators developed EM/PROTECT, a behavioral intervention for depressed EM (elderly mistreatment) victims, to work in synergy with EM mistreatment resolution services that provide safety planning, support services, and links to legal services. PROTECT is built on a model which postulates that chronic stress promotes dysfunction of the cognitive control (CCN) and reward networks, impairing the victims' ability to flexibly respond to the environment and limits their reward activities. PROTECT therapists work with victims to develop action plans to reduce stress, and to increase rewarding experiences. EM/PROTECT has been designed in an iterative process with community EM providers of the New York City (NYC) Department for the Aging (DFTA) to use agencies' routine PHQ-9 depression screening and referral for service. In the current study, the investigators will compare the effectiveness of EM/PROTECT with EM enriched with staff training in linking EM victims to community mental health services (EM/MH). The investigators intend to enroll 80 subjects that will participate in the study for approximately 12 weeks.

Characterization and Treatment of Adolescent Depression

Study Type: Interventional
Start Date: December 28, 2017
Location: Bethesda, Maryland
Eligibility: Ages 10–17, Accepts Healthy Volunteers

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.

Intravenous Ketamine Plus Neurocognitive Training for Depression

Study Type: Interventional
Start Date: December 1, 2017
Location: Pittsburgh, Pennsylvania
Eligibility: Ages 18–60, Does Not Accept Healthy Volunteers

This study has two aims: 1) to characterize the effects of intravenous ketamine on neurocognitive markers in depressed patients; 2) to test the efficacy of a synergistic intervention for depression combining intravenous ketamine with neurocognitive training.

Brain Emotion Circuitry-Targeted Self-Monitoring and Regulation Therapy (BE-SMART)

Study Type: Interventional
Start Date: October 17, 2017
Location: New Haven, Connecticut
Eligibility: Ages 16–24, Does Not Accept Healthy Volunteers

New treatments to help to reduce the emotional dysregulation of mood disorders are critically needed. This is a study of an emotional dysregulation psychotherapy treatment in which subjects will learn skills to help to down-regulate maladaptive emotional responses and learn beneficial, healthy habits. Investigators will perform symptom and behavioral assessments and scanning prior to the treatment and will then repeat scanning, symptom and behavioral assessments at the midpoint, and after the psychotherapy is completed. This collected information will assess whether the treatment can improve functioning of emotion regulation brain circuitry.

Development and Preliminary Trial of a Brief, Portable Health Intervention for Rural Sexual Minority Emerging Adults

Study Type: Interventional
Start Date: October 15, 2017
Locations: New Haven, Connecticut; Worcester, Massachusetts; Johnson City, Tennessee
Eligibility: Ages 18–29, Accepts Healthy Volunteers

The purpose of this study is to test the feasibility of writing interventions specifically designed for lesbian, gay, and bisexual (LGB) emerging adults (ages 18-29) that are aimed at improving the outcomes: depression, suicidality, substance abuse and HIV risk behaviors.

A Closed-loop Assessment and Treatment Platform for Mood Disorders

Study Type: Interventional
Start Date: October 1, 2017
Location: San Francisco, California
Eligibility: Ages 18–60, Does Not Accept Healthy Volunteers

Specific Aim 1: Finalize development of the closed-loop strategy in the Moodify application.

Specific Aim 2: Evaluate the acceptability and feasibility of the Moodify application with the target population to prepare for a large-scale efficacy trial.

Study to Treat Major Depressive Disorder With a New Medication

Study Type: Interventional
Start Date: September 25, 2017
Locations: New York, New York; Houston, Texas
Eligibility: Ages 18–65, Does Not Accept Healthy Volunteers

This project is designed to examine the neuronal KCNQ2/3 potassium (K+) channel subtype as a novel treatment target for mood disorders through the administration of the KCNQ-selective channel opener ezogabine (Potiga, GlaxoSmithKline; FDA-approved for the treatment of seizure disorders).

Volunteer-Delivery of Behavioral Activation

Study Type: Interventional
Start Date: September 15, 2017
Location: Seattle, Washington
Eligibility: Ages 60 and Older, Does Not Accept Healthy Volunteers

In response to large numbers of senior center clients who suffer untreated depression and the dearth of geriatric mental health providers, the investigators have simplified a Behavioral Activation intervention to match the skill set of age-matched lay volunteers available to senior centers (Volunteer BA). This R34 proposes developmental work on delivering Volunteer BA in senior centers, so as to arrive to a sustainable intervention with standardized procedures. The investigators follow with a small randomized controlled trial (RCT) testing the comparative impact of Volunteer BA versus MSW-provided BA on increased client activity and reduced depressive symptoms.

Reducing Fetal Exposure to Maternal Depression to Improve Infant Risk Mechanisms

Study Type: Interventional
Start Date: September 1, 2017
Location: Denver, Colorado
Eligibility: Females, Ages 18 and Older, Does Not Accept Healthy Volunteers

This study evaluates Interpersonal Therapy (IPT) in the treatment of depression among pregnant women with elevated depressive symptoms. Half of the women will be randomized to receive IPT, and the other half will get Treat As Usual, provided via behavioral health in the hospital.

Development of Attention Bias Modification for Depression

Study Type: Interventional
Start Date: September 1, 2017
Location: Austin, Texas
Eligibility: Ages 18–40, Does Not Accept Healthy Volunteers

Although negatively biased attention has a central theoretical and empirical role in the maintenance of depression, there are few behavioral treatments that successfully target and improve this deficit. The current proposal builds upon prior work and aims to further develop an attention bias modification intervention. The investigators propose to develop a highly specific intervention that directly targets negative attention bias and the neurobiology that supports it, using cutting-edge cognitive neuroscience to inform treatment development and improve quality of life of patients whose psychopathology is maintained by negative attention bias.

Collaborative Care for Children's Mental Health Problems

Study Type: Interventional
Start Date: August 1, 2017
Location: Tehran, Iran, Islamic Republic of
Eligibility: Ages 5–15, Does Not Accept Healthy Volunteers

Background: Mental health problems cause a disproportionate burden of disability among children and youth compared to adults. Primary care plays an important role in efforts to prevent and intervene early in the course of child and adolescent mental health problems. While research with adults has shown the feasibility of integrating mental health care into primary care settings, there have been few studies among children and youth. Evidence remains lacking that integration is feasible in diverse settings, that it improves outcomes, and that methods can be developed to address the mixed symptoms of emerging child/youth problems and their overlap with developmental and parental disorders.

Goals: The purpose of this project is to test the effectiveness of adding a child/youth mental health component into an existing collaborative care program for adult mental health problems. The work will refine a framework for efficient cultural adaption and tailoring of an existing child/youth primary care mental health intervention and then test whether the tailored intervention results in improved child and parent outcomes. The work will also provide evidence about the mechanisms by which those outcomes are achieved and what factors influence uptake of the child/youth component by general practitioners (GPs). These results should be generalizable to low and middle income countries and to underserved areas of the US where there are minimal child mental health resources and family physicians provide the bulk of medical care for children and youth.

Methods: The planned work involves the adaptation/tailoring process followed by a trial with 45 GPs already engaged in collaborative care for adults; the trial will study adding collaborative care for children ages 5-15. GPs will be randomly assigned in groups to begin 6-month control periods involving child mental health screening and referral. They will then receive child/youth training and begin second 6-month periods of screening plus ongoing coaching and booster sessions and collaborative management. Primary outcomes will be measured by recruiting and following for 6 months two cohorts of children/youth and their parents (one control, one collaborative care). Data collected from GPs, parents, youth, and the collaborative care data system will allow measurement of key factors that determine the program's success in helping children and families.

Transdiagnostic Brain-Behavior Profiling to Enhance Cognitive Behavioral Therapy Response

Study Type: Interventional
Start Date: July 5, 2017
Location: Chicago, Illinois
Eligibility: Ages 18–65, Accepts Healthy Volunteers

Many patients with Major Depressive Disorder (MDD) and generalized Social Anxiety Disorder (gSAD) are treated with cognitive behavioral therapy (CBT) but few have meaningful improvement. MDD and gSAD are diseases of brain dysfunction that manifest as impaired emotion regulation; CBT teaches emotion regulation strategies but how it works in the brain remains largely unknown. Individual differences in brain function related to emotion regulation may make some patients better suited for CBT and CBT may remedy the brain dysfunction that underlies these disorders. This project will compare CBT with a placebo psychotherapy (i.e., supportive therapy) in MDD and gSAD to test, validate, and refine brain-based markers and examine mechanisms of change to examine how CBT works and for whom.

Improving South African Government Workers' Capacities to Deliver HIV Interventions

Study Type: Interventional
Start Date: June 1, 2017
Locations: Stellenbosch, South Africa; Zithulele, South Africa
Eligibility: Females, Ages 15–49, Accepts Healthy Volunteers

The purpose of this study is to address the United States Office of AIDS Research highest priorities: improving the workforce, reducing health disparities, and addressing HIV comorbidities. UCLA will randomize the government-funded community health workers (CHW) from 16 clinics in matched rural areas in the Eastern Cape in South Africa to either: 1) the Accountable Condition (AC) in which additional monitoring and accountability systems that Philani routinely uses are implemented or 2) a Control Condition (CC), of initial Philani training, but ongoing supervision and monitoring consistent with local government practices.

Neuropharmacologic Imaging and Biomarker Assessments of Response to Acute and Repeated-Dosed Ketamine Infusions in Major Depressive Disorder

Study Type: Interventional
Start Date: May 25, 2017
Location: Bethesda, Maryland
Eligibility: Ages 18–65, Accepts Healthy Volunteers

Background:

Most medications that treat depression take weeks or months to work. Researchers want to develop fast-acting treatments. One dose of ketamine has a rapid antidepressant effect. For most people, this lasts a week or less. Repeated doses of ketamine may help maintain this effect.

Objective:

Main Study: To study the effects of ketamine in treating depression.

Ketamine Metabolites Substudy: To study how ketamine effects brain chemistry.

To study how ketamine effects the brain. This is done by looking at metabolites, which are created when a drug is broken down.

Eligibility:

Main Study: People ages 18-65 with major depressive disorder and healthy volunteers

Ketamine Metabolites Substudy: Healthy volunteers ages 18-65

Design:

Main Study:

Participants will be screened in another study, with:

- Medical and psychiatric history

- Psychiatric and physical exam

- Blood, urine, and heart tests

Participants will be inpatients at NIH for 4 phases totaling 14-20 weeks.

Phase I (2-7 weeks):

- Gradually stop current medications

- MRI: Participants lie and perform tasks in a machine that takes pictures of the body.

- Mood and thinking tests

- Blood and urine tests

- Sleep test: Monitors on the skin record brain waves, breathing, heart rate, and movement during sleep.

- Transcranial magnetic stimulation: A coil on the scalp gives an electrical current that affects brain activity.

- Stress tests: Electrodes on the skin measure reactions to loud noises or electric shocks.

Phase I tests are repeated in Phases II and III and in the final visit.

Phase II (4-5 weeks):

- 4 weekly IV infusions of ketamine or a placebo during an MRI or MEG. For the MEG, a cone over the head records brain activity.

Phase III (optional):

- 8 infusions of ketamine over 4 weeks

Phase IV (optional):

- Symptoms monitoring for 4 weeks

- Participants will have a final visit. They will be offered standard treatment at NIH for up to 2 months.

Ketamine Metabolites Substudy:

Participants will be screened in another study, with:

- Medical and psychiatric history

- Psychiatric and physical exam

- Blood, urine, and heart tests

Participants will be inpatients at NIH for 4 days.

Study Procedures:

Mood and thinking tests

Blood and urine tests

1 infusion of ketamine

Spinal tap and spinal catheter: Used to get samples of cerebrospinal fluid (CSF). This is a fluid that moves around and within the brain and spinal cord. Studying CSF will help us learn how ketamine effects brain chemistry

Neural Mechanisms of Monoaminergic Engagement in Late-life Depression Treatment Response (NEMO)

Study Type: Interventional
Start Date: May 24, 2017
Location: Pittsburgh, Pennsylvania
Eligibility: Ages 60 and Older, Does Not Accept Healthy Volunteers

The Department of Psychiatry at the University of Pittsburgh is conducting a research study to learn about the changes that occur in the brain when individuals suffer from and then are treated for depression. The NEMO study has two main purposes. The first is to provide medication treatment to individuals ages 60 and older who are currently depressed.

The second part of the study involves completing a series of 4 MRIs, which assess changes in brain function over the course of treatment. This research may help investigators to develop faster and more effective treatment plans in the future, as brain responses that are detected early in treatment may predict how well an individual will respond to antidepressant medication.

Storytelling Video Intervention for Depressed Primary Care Patients - Pilot Trial

Study Type: Interventional
Start Date: May 1, 2017
Location: Pawtucket, Rhode Island
Eligibility: Ages 18 and Older, Does Not Accept Healthy Volunteers

The overall aim of this program of research is to refine and test a newly developed storytelling video intervention (sTVi) for depressed primary care patients.

The purpose of the proposed project is to establish the feasibility, acceptability, and preliminary effects of the intervention for an eventual large-scale randomized clinical trial which would test the efficacy of sTVi in comparison to a control condition.

To achieve the specific aims, the investigators will conduct a pilot randomized clinical trial (n = 40), with two treatment arms: antidepressant treatment as usual (aTAU) + sTVI vs aTAU + attention control videos.

Remote Supervision for Implementing Collaborative Care for Perinatal Depression

Study Type: Interventional
Start Date: April 1, 2017
Location: Seattle, Washington
Eligibility: Females, Ages 18–45, Does Not Accept Healthy Volunteers

This study evaluates the impact of a longitudinal remote consultation (LRC) implementation strategy for collaborative care depression treatment among perinatal women receiving care from federally qualified health centers (FQHCs). All participating health centers will receive training in collaborative care. Cluster randomization will be used to assign the addition of LRC to select health centers. Differences in implementation success, clinical outcomes, and costs will be compared after a 12 month implementation period and 13-21 month sustainment period.

Lifestyle Intervention for Young Adults With Serious Mental Illness

Study Type: Interventional
Start Date: March 1, 2017
Locations: Cambridge, Massachusetts; Manchester, New Hampshire
Eligibility: Ages 18–35, Does Not Accept Healthy Volunteers

This is a four year project evaluating the effectiveness of a group-based lifestyle intervention (PeerFIT) supported by mobile health (mHealth) technology and social media compared to Basic Education in fitness and nutrition supported by a wearable Activity Tracking device (BEAT) in achieving clinically significant improvements in weight loss and cardiorespiratory fitness in young adults with serious mental illness (SMI).

Integrating HIV and Depression Self-Care to Improve Adherence in Perinatal Women

Study Type: Interventional
Start Date: January 31, 2017
Location: New Delhi, India
Eligibility: Females, Ages 18 and Older, Does Not Accept Healthy Volunteers

Depression is a common perinatal complication that can have a profound, adverse effect on maternal and child health outcomes. The proposed study will directly address this important, but understudied area by evaluating the feasibility and preliminary effect of an innovative, integrated intervention approach, BEST-maCARE [Better Education, Support, Treatment for maternal Capacity, Adherence, REtention in care]. The multi-component intervention is guided by a model drawn from self-regulation and bioecological systems theory. Proactive counseling personalized to the patient and socio-cultural context is delivered by trained clinic personnel (e.g., counselors) to build problem solving and coping skills and linkages to mental health, HIV treatment and ancillary services. The theory-guided intervention approach has been found effective in improving the health behavior and outcomes (e.g., virologic) of vulnerable, marginalized HIV+ women and men in rural and urban settings in the US (AI38858-ACTG 731; R01NR05108). Although the investigators formative research suggests that it is well suited for the target population, its usefulness in addressing significant gaps in care among perinatal women.

l women with co-morbid conditions in a different socio-cultural, limited resource setting has not been studied.

ECT Pulse Amplitude and Medial Temporal Lobe Engagement

Study Type: Interventional
Start Date: October 31, 2016
Location: Albuquerque, New Mexico
Eligibility: Ages 50–80, Does Not Accept Healthy Volunteers

Electroconvulsive therapy (ECT) remains the gold-standard treatment for patients with depressive episodes. During a typical four-week ECT series, most depressive episodes will respond to treatment and people will improve their level of functioning (return to work or family). Independent of the antidepressant effect of ECT, many patients experience transient memory impairment. This investigation will examine the impact of one ECT parameter (pulse amplitude or current) on brain changes (structure of connections within the brain) and clinical outcomes. The goal of this investigation is to determine the optimal parameter for an individual patient that will maintain the clinical response (reduce depression severity) and minimize side effects (eliminate memory issues related to treatment).

Motivating Our Mothers 2

Study Type: Interventional
Start Date: October 31, 2016
Location: Sacramento, California
Eligibility: Females, Ages 21–65, Does Not Accept Healthy Volunteers

Mothers with symptoms suggesting clinical depression can be identified and potentially motivated to seek further care during pediatric visits for their young children. The best ways for pediatric providers to encourage mothers to seek further evaluation and treatment for their depressive symptoms are not known. The investigators plan to provisionally optimize a pediatric office-based intervention that the investigators developed to motivate mothers who may be depressed to seek further care and, thereby to improve the well-being of women from diverse backgrounds and their children.

A Study Examining Adolescents With Non-Suicidal Self-Injury

Study Type: Observational
Start Date: August 31, 2016
Location: Minneapolis, Minnesota
Eligibility: Females, Ages 12–16, Accepts Healthy Volunteers

This study will examine longitudinal brain development in young adolescent girls with a history of Non-Suicidal Self-Injury (NSSI). Specifically, three constructs outlined by the the Research Domains Criteria (RDoC) will be examined through self-assessment, MRI, and a cognitive battery.

Mental Health Pathways in Internet Support Groups

Study Type: Interventional
Start Date: June 30, 2016
Location: Pittsburgh, Pennsylvania
Eligibility: Ages 18 and Older, Accepts Healthy Volunteers

People facing serious health threats increasingly use Internet health support communities to obtain informational support, emotional support and other resources. This study introduces software algorithms similar to those used by social media sites to put people in touch with helpful information and social interactions. Participants from the American Cancer Society's Cancer Support Network will have access to this online support group using the default interface that orders content by broad content category and date or with a new interface that highlights communication content and people that match users' interests and needs.

Testing the Neuroscience of Guided Learning in Depression

Study Type: Interventional
Start Date: May 1, 2016
Location: Roanoke, Virginia
Eligibility: Ages 18–55, Accepts Healthy Volunteers

Major depression is a prevalent and impairing illness. To better understand the basic science and treatment of depression, the investigators study the behavioral and brain processes associated with learning in depression and how potential disruptions in learning may be repaired. Understanding different methods that change learning may lead to novel treatments that contribute to recovery in people with depression.

Addressing Psychosocial Comorbidities in HIV Treatment and Prevention

Study Type: Interventional
Start Date: March 31, 2016
Location: Miami, Florida
Eligibility: Ages 18–65, Does Not Accept Healthy Volunteers

Project AProaCH is an open pilot trial of a cognitive behavioral therapy (CBT) for individuals with HIV with various psychological comorbidities, which the investigators call "syndemics". Syndemics are co-occurring psychosocial problems that interact with each other and with health behavior such as HIV sexual transmission risk behavior and adherence to self care.

Community Study of Outcome Monitoring for Emotional Disorders in Teens

Study Type: Interventional
Start Date: January 31, 2016
Location: West Hartford, Connecticut
Eligibility: Ages 12–18, Does Not Accept Healthy Volunteers

Emotional disorders, including an array of anxiety and depressive syndromes, are the most common psychiatric disorders among adolescents, are highly comorbid, and severely impair the lives of youth and their families. Extant evidence-based therapies target only single disorders or symptom domains, are often not adopted by community mental health center (CMHC) clinicians, and have only modest effect sizes. To improve the clinical outcomes of these youth, the proposed study tests the effectiveness of two novel interventions (a transdiagnostic intervention, the Unified Protocol for the Treatment of Emotional Disorders in Adolescents, and a measurement and feedback system, the Youth Outcomes Questionnaires) relative to usual care in CMHCs.

Mechanism of Antidepressant-Related Dysfunctional Arousal in High-Risk Youth

Study Type: Interventional
Start Date: December 31, 2015
Locations: Stanford, California; Cincinnati, Ohio
Eligibility: Ages 12–17, Accepts Healthy Volunteers

A 16-week double blind, placebo-controlled investigation of escitalopram in adolescents with depression and/or anxiety with a family history of Bipolar Disorder. Subjects will be evaluated using semi-structured diagnostic interviews and symptom ratings, participate in a MRI scan and then randomized to treatment. Following randomization, high-risk youth will have visits every week for the first 4 weeks of treatment then biweekly up to 16 weeks during which time tolerability and ratings will be performed. MRI scan will be repeated at week 4.

Neural Basis of Meal Related Interoceptive Dysfunction in Anorexia Nervosa

Study Type: Interventional
Start Date: October 31, 2015
Location: Tulsa, Oklahoma
Eligibility: Ages 18–55, Accepts Healthy Volunteers

This study aims to identify the brain regions responsible for encoding cardiorespiratory 'interoceptive' sensations and determine whether they are dysfunctional in individuals affected by eating disorders, anxiety, depression, or brain injury. By evaluating the same interoceptive sensations across different human illnesses, the investigators hope to provide convergent evidence resulting in identification of core underlying neural processes, and to discern relative contributions in each condition.

Neurobiology of Suicide

Study Type: Interventional
Start Date: September 5, 2015
Location: Bethesda, Maryland
Eligibility: Ages 18–70, Accepts Healthy Volunteers

Background:

There are no good treatments for people considering suicide. Researchers want to study suicide with questions, blood tests, brain imaging, and sleep studies. They hope to better understand suicide, so they can help suicidal people.

Objective:

To understand what happens in the brain when someone has thought about or attempted suicide.

Eligibility:

Group 1: Adults ages 18 70 who have thought about or attempted suicide recently

Group 2: Adults ages 18 70 who have thought about or attempted suicide in the past

Group 3: Adults ages 18 70 who have depression or anxiety, but have never thought about suicide

Group 4: Healthy volunteers the same ages.

Design:

Participants will be screened in another protocol. Adults who have recently thought about or attempted suicide must be referred by a doctor. They may do up to 3 phases of this study. Groups 2, 3 and 4 will do only Phase 1 and will not get ketamine.

Phase 1: 1 week in hospital. Participants will have:

Physical exam.

Questions about thoughts and feelings.

Thinking and memory tests and simple tasks.

Blood and urine tests.

Two MRI scans. Participants will lie on a table that slides into a metal cylinder that takes pictures. They will have a coil over their head and earplugs and do a computer task.

Sleep test. Disks and bands will be placed on the body to monitor it during sleep.

Magnetic detectors on their head while they perform tasks.

A wrist monitor for activity and sleep.

Lumbar puncture (optional). A needle will collect fluid from the back.

Shock experiments (optional). Participants will observe pictures and sounds and feel a small shock on the hand.

Phase 2: 4 days in hospital. A thin plastic tube will be placed in each arm, one for blood draws, the other to get the drug ketamine once. Participants will repeat most of the Phase 1 tests.

Phase 3: up to 4 more ketamine doses over 2 weeks.

Participants will have follow-up calls or visits at 6 months and then maybe yearly for 5 years.

Inflammation-related Alterations in Neurocircuitry: Reversal With Levodopa

Study Type: Interventional
Start Date: July 31, 2015
Location: Atlanta, Georgia
Eligibility: Ages 18–65, Does Not Accept Healthy Volunteers

The purpose of this study is to learn more about the changes that happen in the brain and the body when a person is depressed. This study will determine if the level of inflammation in the body is related to symptoms of depression, how well the person thinks, and how certain brain regions communicate.

Antidepressant Effects of the Glycine Receptor Antagonist AV-101 (4-chlorokynurenine) in Major Depressive Disorder

Study Type: Interventional
Start Date: June 19, 2015
Location: Bethesda, Maryland
Eligibility: Ages 18–65, Does Not Accept Healthy Volunteers

Background:

- Drugs and talk therapy help treat depression, but these treatments usually take quite a bit of time to work. Ketamine is a fast-acting antidepressant, but it has side effects like unusual dreams and experiences. The drug AV-101 may have the same antidepressant effects but fewer side effects. Researchers want to see if it is effective and safe for people with major depressive disorder.

Objective:

- To see if the drug, AV-101 is safe and if it treats symptoms of major depressive disorder.

Eligibility:

- Adults ages 18-65 with major depression without psychotic features.

Design:

- Participants will be screened under a separate protocol.

- Participants will stay in the hospital for 12-14 weeks.

- Phase 1 (2-7 weeks): participants will stop taking their medicines then not take any for 2 weeks. They will have several scans and other procedures.

- Phase 2 (6-7 weeks): 2 weeks each of study drug and placebo once a day, with 2 weeks of no drugs in between.

- Participants will have:

- Physical exams

- Interviews

- Frequent blood collection. A needle will place a small plastic tube in the arm. Some blood samples will be taken through this tube.

- 2 spinal taps (optional). The back will be numbed. A needle will insert a catheter between back bones. That will be left in for up to 30 hours. Spinal fluid will be collected through it.

- 5 scans. Participants will lie in a machine with a magnetic field. The machine takes pictures of the brain and brain chemicals.

- At the end of the study, participants will have medical evaluation, questions, and blood tests. Some may continue treatment at the clinic.

miRNAs, Suicide, and Ketamine - Plasma Exosomal microRNAs as Novel Biomarkers for Suicidality and Treatment Outcome

Study Type: Interventional
Start Date: April 30, 2015
Location: Birmingham, Alabama
Eligibility: Ages 18–65, Accepts Healthy Volunteers

The purpose of this study is to examine whether neural-derived exosomal miRNAs are differentially expressed that are specific to suicidal ideation or behavior, and which by affecting specific miRNA targets and pathways, are associated with suicidal behavior and response to ketamine. The following groups of subjects will be examined: 1) major depressive disorder (MDD) with a recent suicide attempt (in past 2 weeks), 2) MDD with serious ideation (in the past 7 days) without recent suicide attempt (in the past 6 months), 3) MDD without clinically significant suicidal ideation (in the past 7 days) or recent suicide attempt (in the past 6 months), and 4) healthy controls. Both suicidal and non-suicidal MDD will be given ketamine (0.5 mg/kg, IV) and blood will be drawn at predose, 30 min, 180 min, 24 hours, and 14 days post-infusion to measure changes in miRNAs.

Improving Mental Health Through Integration With Primary Care in Rural Karnataka

Study Type: Interventional
Start Date: February 28, 2015
Location: Bangalore, Karnataka, India
Eligibility: Ages 30 and Older, Does Not Accept Healthy Volunteers

This cluster Randomized Controlled Trial was designed to implement and evaluate the effects of a multi-level intervention designed to integrate mental health treatment into rural primary health clinics in South India using a collaborative care model.

Effectiveness of a Unified Transdiagnostic Treatment in Routine Care

Study Type: Interventional
Start Date: December 31, 2014
Location: Boston, Massachusetts
Eligibility: Ages 18–100, Does Not Accept Healthy Volunteers

The purpose of this study is to examine effectiveness and implementation for the Unified Protocol for the Transdiagnostic Treatment of Emotional Disorders in trauma exposed veterans.

The ISLAND Study: InSuLa Assessed Needs for Depression

Study Type: Interventional
Start Date: September 30, 2014
Location: Atlanta, Georgia
Eligibility: Ages 18–55, Does Not Accept Healthy Volunteers

While there are many effective options for treating a major depressive episode, there are no clinical markers that predict the likelihood of remission with an initial trial of either an antidepressant medication or psychotherapy. The goal of this study is to test how brain function changes in depress patients treated with cognitive behavioral therapy (CBT) compared to patients treated with escitalopram ((s-CIT) - Lexapro®), an FDA approved antidepressant. The study aims to determine if bran scan findings might help physicians to select the most effective antidepressant treatment for an individual patient.

At total of 150 male and female outpatients who are between 21-55 years old will be enrolled. Participation in the study will last from 14-26 weeks.

Subjects will be randomized to receive either escitalopram (s-CIT) or CBT for 12 weeks. Resting-state positron emission tomography (PET) and BOLD functional magnetic resonance imaging (fMRI) scans will be done before the treatment begins, and again at the end of treatment (week 12). Non-responders to s-cIT or CBT will be crossed over to receive an additional 12 weeks of treatment with the alternative intervention.

Family Cognitive Behavioral Therapy for Preventing Depression in Children

Study Type: Interventional
Start Date: August 1, 2014
Location: Nashville, Tennessee
Eligibility: Ages 9 and Older, Does Not Accept Healthy Volunteers

This study will determine the effectiveness of cognitive behavioral therapy (CBT) versus educational treatment in preventing depression in the children of parents with a history of depression.

Biomarkers of Fast Acting Therapies in Major Depression

Study Type: Interventional
Start Date: June 30, 2014
Location: Los Angeles, California
Eligibility: Ages 18–64, Does Not Accept Healthy Volunteers

The drug Ketamine, available in medical practice since the late 1960s, is currently used for inducing general anesthesia or sedation during medical procedures. When given slowly as an injection into a vein, ketamine is shown to produce a very rapid effect on depression and to improve depressive symptoms within hours to days. By studying patients who receive a ketamine IV infusion, as an add-on treatment for depression, investigators may start to understand how changes in the brain or in gene function relate to getting better over a very short period of time. In this study, the investigators will enroll 60 patients currently ill with major depression selected to receive IV ketamine therapy under medical supervision. To study neurobiological changes relating to symptom improvement, the investigators will use advanced brain scans to measure brain structure, chemistry and function. Blood samples will measure changes in gene regulation and immune system response. Although some people have a rapid antidepressant response to ketamine, others do not respond. Also, antidepressant effects after ketamine usually wear off within days to weeks. We will determine if up to four doses of ketamine delivered two to three times a week may prolong antidepressant response to ketamine therapy. To determine the durability of ketamine treatment for depression, patients will be monitored by phone and via electronic devices twice a week for up to five weeks and will return for a final assessment when their symptoms return. For this trial, brain and blood sample measurements will occur before and after a patient receives their first ketamine infusion. Patients who do not remit after an initial dose of ketamine, will receive up to three additional ketamine treatments. Mood will be measured 24-hours after each subsequent ketamine infusion and brain and blood measurements be repeated at the time of remission or after the fourth ketamine infusion if remission does not occur. Patients will return for a final brain scan and blood sample when their depressive symptoms return or at five weeks if they continue remission. Investigators will able to see how changes brain measurements, gene regulation and immune response relate to improvements and relapse of depressive symptoms with ketamine IV therapy. The ketamine infusion sessions will occur at a special research unit (CTRC) at UCLA.

Neuroimaging Epigenetics of Prospective Postpartum Depression Biomarkers

Study Type: Observational
Start Date: May 31, 2014
Location: Baltimore, Maryland
Eligibility: Females, Ages 18–65, Accepts Healthy Volunteers

Through a recent cross species translational experiment, researchers have identified a set of epigenetic marks capable of predicting postpartum depression with greater than 85% accuracy. The researchers are looking to identify a group of women from both the general population and those with a history of mood disorders who are at risk for postpartum depression and obtain brain imaging data at a postpartum time period prior to the onset of depressive symptoms and compare it with those obtained during depressive episodes. The researchers will also evaluate the efficacy of postpartum depression biomarker prediction.

Ask Suicide-Screening Questions to Everyone in Medical Settings (asQ em): Development of a Suicide Risk Screening Instrument for Adult Medical Inpatients

Study Type: Observational
Start Date: May 14, 2014
Locations: Bethesda, Maryland; Providence, Rhode Island; Fort Worth, Texas
Eligibility: Ages 18 and Older, Does Not Accept Healthy Volunteers

Background:

- Suicide is the 10th leading cause of death for U.S. adults. Medically ill people are at an increased risk of suicide. Most people who have killed themselves went to a healthcare provider within 3 months of their death. More and more, hospitals are being asked to assess people for signs of suicide risk so that they can get the help they need. If nurses and doctors can find out who is at risk they can make sure these people get help in the hospital.

The asQ em (Ask Suicide-Screening Questions to Everyone in Medical Settings) is a brief questionnaire. It was created to detect suicidal thoughts and behaviors in hospitalized people. Researchers would like to further develop this tool and figure out which are the best questions to ask patients.

Objective:

- To determine the best questions for healthcare providers to ask people with medical illnesses to see if they are having suicidal thoughts or planning to hurt themselves.

Eligibility:

- NIH Clinical Center patients over age 18.

Design:

- Participants will be asked questions about how they have been feeling in the past few weeks. They will be asked questions about depression, anxiety, and suicidal thoughts and behaviors. They also will be asked some background questions.

- It will take approximately 15 to 30 minutes to answer the questions.

Integrated Chronotherapy for Perinatal Depression

Study Type: Interventional
Start Date: January 31, 2014
Location: Providence, Rhode Island
Eligibility: Females, Ages 18–40, Does Not Accept Healthy Volunteers

Perinatal depression is a common and serious mood disorder that increases morbidity and mortality in new mothers and results in poor infant/child outcomes. Current therapies often fail to produce recovery or are poorly tolerated and many pregnant women seek non-pharmacologic therapy or forgo treatment when non-pharmacologic options are not available. Expectant and new mothers who suffer from circadian rhythm disruption are at risk for perinatal depression. This R34 Pilot Effectiveness Studies and Services Research Grant seeks to test whether an Integrated Chronotherapy (IC) intervention can be implemented in an outpatient psychiatry setting to improve treatment outcomes for patients with perinatal depression. IC is a multicomponent treatment consisting of bright light therapy, sleep phase advance, and sleep stabilization/restriction that targets the Research Domain Criteria (RDoC) constructs of circadian rhythms, sleep-wake behavior, social rhythms, and arousal. We will assess the feasibility, safety, and acceptability of an IC intervention for perinatal depressin by testing the treatment in expectant mothers diagnosed with major depressive disorder during 3rd trimester of pregnancy. We will randomize patients to either: (a) usual care (UC, n = 20) or (b) IC+UC (n = 20). IC+UC will have pregnancy and postpartum components and will be administered via an individualized case formulation approach tailored to each patient. After a baseline assessment, IC will be prescribed during 5 dedicated clinical visits: three during 3rd trimester of pregnancy and 2 in the postpartum period. UC will consist of medication administered by a perinatal psychiatrist and/or psychotherapy. UC will be quantified in both groups to evaluate differences between the IC+UC and UC groups. Mood will be measured in both groups by blinded clinician interview and patient self-report. We will assess the safety profile of the IC intervention with evaluation of side effects/adverse events. Importantly, the study will also examine the putative mechanisms by which IC is hypothesized to work and the "dose" of IC received by patients in the IC+UC group. All participants will wear wrist actigraphy/light monitors continuously during weeks 28-40 of pregnancy and postpartum weeks 2-6 to assess light exposure and sleep duration and timing. Circadian phase (measured with salivary dim light melatonin onset) will be measured at baseline during pregnancy (~30 weeks gestation), at 36 weeks gestation, and at postpartum week 6. This pilot will allow us to refine the IC intervention for future integration into various clinical settings and establish an infrastructue for a larger (R01-scale) trial, including measuring acceptability of IC among UC clinicians and implementing web-based data collection to facilitate data sharing in the planned R01. Perinatal IC could have major public health impact due to the high prevalence of perinatal depression and its negative effects on mothers and their children. This project represents a first step toward achieving this goal, as it will provide the pilot data necessary to prepare for a larger scale intervention study focused on providing non-pharmacologic therapies and improving outcomes for women with perinatal depression.

Neural Components Underlying the Treatment of Adolescent Depression

Study Type: Interventional
Start Date: October 31, 2012
Location: Belmont, Massachusetts
Eligibility: Females, Ages 13–18, Accepts Healthy Volunteers

The goal of the study is to examine how cognitive behavioral therapy (CBT), a common treatment for adolescent depression, affects brain functioning. Depressed adolescents will complete an initial assessment consisting of an interview, questionnaires, computer tasks, and an EEG recording. EEG (electroencephalography) measures brain activity by recording the electrical activity along the scalp caused by the firing of neurons within the brain. They will then complete 12 sessions of cognitive behavioral therapy, which will be 50 minutes long and held once a week for 12 weeks. Before their third therapy session, participants will complete a computer task while EEG data are recorded. After completing the treatment, the participants will complete a final assessment, which will include questionnaires, computer tasks, and an EEG recording. They will also complete follow-up assessments over the phone 1, 3, and 6 months after completing the treatment.

This study will also include healthy control participants. They will complete an initial assessment consisting of an interview, questionnaires, computer tasks, and an EEG recording. Three weeks later, they will return to complete a behavioral task while EEG data are recorded. Twelve weeks after the initial assessment, they will complete a final assessment, which will include questionnaires, computer tasks, and an EEG recording.

Emotional and Cognitive Control in Late-Onset Depression

Study Type: Interventional
Start Date: July 31, 2012
Location: White Plains, New York
Eligibility: Ages 60–85, Accepts Healthy Volunteers

This study may help identify how abnormalities in brain systems that control the ability to ignore irrelevant information may contribute to the development of depression in older adults.

Antidepressant Response in the Treatment of Depressive Symptoms and Frailty Characteristics in Older Adults

Study Type: Interventional
Start Date: September 30, 2011
Location: New York, New York
Eligibility: Ages 60–95, Does Not Accept Healthy Volunteers

The goal of this open-administration treatment study of citalopram (or duloxetine) is to evaluate the effect of antidepressant medication on treating the syndrome of "frailty" in older adults with depressive symptoms. Patients with significant depressive symptoms (defined as CES-D (Center for Epidemiological Studies - Depression scale) > 10) and 1 or more symptoms of the frailty syndrome (exhaustion, decreased energy, weight loss, decreased grip strength, and slow/unsteady gait) will be evaluated and treated with citalopram (or duloxetine) for 8 weeks to test whether antidepressant medication improves both the syndrome of frailty and depressive symptoms. Patients evaluated at the Adult and Late Life Depression clinic and eligible to participate in the study will be treated with an antidepressant medication and assessed on the primary outcome variables (characteristics of frailty, depressive symptoms) as well as on secondary variables which include cognition (global cognition, episodic memory, executive function), and function (physical mobility, instrumental activities of daily living, and social functioning) prior to treatment initiation and following 8-weeks of treatment. The hypotheses for this protocol predict that we will discover a significant improvement on both frailty characteristics and depressive symptoms in this clinical population when treated with antidepressant medication (citalopram or duloxetine).

Cellular Aging and Neurobiology of Depression Study

Study Type: Interventional
Start Date: December 31, 2010
Location: San Francisco, California
Eligibility: Ages 21–60, Accepts Healthy Volunteers

We are conducting an eight week longitudinal study to learn if blood levels of certain naturally occurring compounds and genetic markers differ between patients with depression and healthy adults who are not depressed, and if any such differences relate to memory performance, mood, and neurobiology.

We will do this by comparing the unmedicated depressed patients with matched healthy controls at baseline and then following the depressed patients over the course of eight weeks of standardized antidepressant treatment to gauge which baseline abnormalities normalize over the course of treatment.

Brain Imaging and Computer Games in Children With Either Bipolar Disorder, ADHD, Anxiety or Healthy Controls

Study Type: Observational
Start Date: July 31, 2007
Location: East Providence, Rhode Island
Eligibility: Ages 7–17, Accepts Healthy Volunteers

The purpose of this research is to learn more about how children with mental health problems, including bipolar disorder (BD), attention deficit hyperactivity disorder (ADHD), and generalized anxiety disorder (GAD), differ from children without these problems. The investigators want to understand how these 4 groups of children differ in brain activity, function, and structure.

Treatment Response of Geriatric Depression

Study Type: Interventional
Start Date: May 31, 2007
Location: White Plains, New York
Eligibility: Ages 60–90, Accepts Healthy Volunteers

The purpose of this study is to examine the relationship between brain electrical activity in elderly depressed patients and response to antidepressant medication treatment. Elderly patients with depression will be treated for 12 weeks with an antidepressant medication commonly used in clinical practice called escitalopram (Lexapro). Brain electrical activity will be assessed using electrophysiological tests. Researchers are interested in whether the brain electrical activity of elderly people with depression before they start the medication can tell us who amongst them will improve with antidepressant treatment and to what extent. They will also determine whether patients' brain electrical activity during the 12 weeks of medication treatment will change in any way and whether this change will be linked with a change in the severity of their depression. Researchers hope that information gained from this study will help to better understand the brain processes associated with depression and its successful treatment.

Family Study of Affective and Anxiety Spectrum Disorders

Study Type: Observational
Start Date: October 30, 2003
Location: Bethesda, Maryland
Eligibility: Ages N/A–60, Accepts Healthy Volunteers

This study will examine how depression, anxiety, and migraine run in families. It will help in defining the risk factors for physical, mental, and health problems-as well as define ways that those problems may be prevented and treated.

A broad range of ages among family members will be included to evaluate the patterns of how these disorders are expressed throughout people's lives. Children of all ages will be included, and those ages 8 to 17 will be interviewed directly.

Assessments will be collected through criteria of the Diagnostic and Statistical Manual of Mental Disorders IV as well as the spectrum, or range, of mood disorders and co-existing conditions. A member of the study team will visit the participants at home or will do an interview by telephone. Participation will take approximately 3 to 4 hours. Children will complete questionnaires given by the research team as well as questionnaires that they will do by themselves. The questions will pertain to the children's health, including physical and mental health and medical history, social relationships, problems, skills, and ways of dealing with important or stressful issues in their lives. These questionnaires will take up to 1 hour to complete.

Health history gathered from adult participants will pertain to height, weight, exercise, and general function. Women will be asked about the use of oral contraceptives, estrogen, and progesterone. In addition, there will be questionnaires on personality and temperamental traits, that is, behavior and impulsiveness. Questions will also involve social intuition, family and other environmental factors, general functioning, and basic demographics such as ethnicity, race, socioeconomic status, marital status, education level, and employment history.

Families enrolled in this phase of the research will be invited to participate in the next phase. There would be follow-up to evaluate the development of mood disorders, subtypes, and syndromes across the lifespan.

The Psychobiology of Childhood Temperament

Study Type: Observational
Start Date: May 12, 2003
Locations: Bethesda, Maryland; College Park, Maryland
Eligibility: Ages N/A–25, Accepts Healthy Volunteers

The purpose of this study is to use brain imaging technology to examine brain changes that occur in children when they are exposed to various kinds of emotional tasks and to determine if these changes are related to the child's temperament.

Studies suggest that the risk for developing mood and anxiety disorders in preschool children may be linked to differences in temperament. The relationship between temperament and risk or resilience may reflect the influences of brain activity on behavior at different stages of childhood development. Behavioral inhibition and mood or anxiety disorders have been linked to disturbances in the circuitry of several areas in the brain. However, the involvement of this circuitry in temperament remains unclear. This study will use functional magnetic resonance imaging (fMRI) to examine the function of different parts of the brain in children who have previously undergone temperament studies and have had their temperaments classified.

Two sets of studies will be performed in the current protocol. A small set of pilot studies will be performed in infants, by staff at the University of Maryland. In terms of the studies among infants, these subjects will initially be contacted by staff at Maryland and then will be seen at the NIH for up to three visits lasting between 4- to 5- hours during the first year of life. These subjects also will undergo visits at the University of Maryland throughout the first year of life.

This study will comprise up to four clinic visits. At Visit 1, children and their parents will meet with study staff individually and together for psychiatric interviews. Children will undergo a physical examination, medical history, a urine drug test, and practice in an fMRI simulator. Saliva samples will be collected from the children and tests will be given to assess stage of puberty, temperament, intelligence, feelings, experiences, and behavior. Other visits include fMRI scans of the brain and other tasks.

Studies of Brain Function and Course of Illness in Pediatric Bipolar Disorder

Study Type: Observational
Start Date: October 29, 2001
Location: Bethesda, Maryland
Eligibility: Ages 7–25, Accepts Healthy Volunteers

This study seeks to learn more about the symptoms of severe mood dysregulation in children and adolescents ages 7-17. Children and adolescents with severe mood dysregulation (SMD) display chronic anger, sadness, or irritability, as well as hyperarousal (such as insomnia, distractibility, hyperactivity) and extreme responses to frustration (such as frequent, severe temper tantrums). Researchers will describe the moods and behaviors of children with these symptoms and use specialized testing and brain imaging to learn about the brain changes associated with this disorder.

Evaluation of Patients With Mood and Anxiety Disorders and Healthy Volunteers

Study Type: Observational
Start Date: September 21, 2001
Location: Bethesda, Maryland
Eligibility: Ages 3–99, Accepts Healthy Volunteers

The purpose of this protocol is to allow for the careful screening of patients and healthy volunteers for participation in research protocols in the Experimental Therapeutics and Pathophysiology Lab (ETPB) at the National Institute of Mental Health (NIMH) and for the collection of natural history data. In addition the protocol will allow clinicians to gain more experience in the use of a variety of polysomnographic and high-density EEG recordings. Subjects in this protocol will undergo an evaluation which may include: a psychiatric interview; a diagnostic interview; rating scales; a medical history; a physical exam; brain magnetic resonance imaging (MRI); electroencephalography (EEG); electrocardiography (EKG), magnetoencephalography (MEG); blood, saliva and urine laboratory evaluation; and a request for medical records. Subjects may also be asked to complete questionnaires about attitudes towards research and motivation for research participation. The data collected may also be linked with data from other mood and anxiety disorder protocols (e.g., brain imaging, DNA, psychophysiology tests, treatment studies, etc) for the purposes of better understanding the diagnosis, pathophysiology, and treatment response of patients with mood disorders. Parents of minors will be interviewed. Upon conclusion of the screening process, subjects will either be offered participation in a research protocol and will sign the appropriate informed consent, or will be considered not appropriate for participation in research and will be referred back into the community. The current protocol thus serves as an entry point for individuals with mood or anxiety disorders or healthy volunteers to enter NIMH IRB approved ETPB protocols.

Clinical Trial of Fluoxetine in Anxiety and Depression in Children, and Associated Brain Changes

Study Type: Observational
Start Date: June 27, 2001
Location: Bethesda, Maryland
Eligibility: Ages 8–40, Accepts Healthy Volunteers

This study uses functional magnetic resonance imaging (fMRI) to learn how the brain functions in adolescents receiving fluoxetine (Prozac) cognitive behavioral therapy (CBT) or interpersonal therapy (IPT) for anxiety or depression in children/adolescents.

All participants will receive interviews to assess how they are doing in general, including general mood, degree of nervousness and behavior. Each participant and one of his or her parents will be interviewed separately and together. Those electing the medication study will also receive a physical examination. Participants are asked to complete tasks involving problem-solving and memory that involve looking at pictures, remembering things, testing reaction times, and making simple choices.

Participants with anxiety or depression will first meet with a psychiatrist or psychologist for two weekly sessions of talk therapy.

Those who remain anxious or depressed after these 2 weeks will have the 3 options based on their choice: 1) treatment with fluoxetine daily for 8 weeks 2) cognitive-behavioral therapy or interpersonal therapy (two kinds of talk therapy) once a week for 8 weeks 3) a random assignment (50% chance) to either placebo or fluoxetine for 8 weeks. In addition, subjects also will be randomly and blindly assigned to receive either an active computer-based training task or an inactive computer-based training task, administered as part of the other,along with their medication or talk -therapy treatment. The active training is thought to help anxiety whereas the inactive training is thought to have no effect. The purpose of this part of the study is to understand the best way to help children and adolescents who are having problems with anxiety. However, more research is needed to find the best way to help such children and adolescents. During and after the 8 weeks of treatment, each participant will complete verbal and written symptom ratings. Blood samples will be drawn for laboratory tests before drug treatment and after it ends.

Those who have not improved by the end of the study will be offered other treatment for 1 to 3 months, and the clinicians will help with finding subsequent aftercare. Those who improve with treatment will continue therapy at NIH until an outside physician is able to assume responsibility for monitoring medication.

FOR MORE INFORMATION REGARDING THIS STUDY CALL THE CORE PHONE NUMBER: 301-496-5645

The Role of Hormones in Postpartum Mood Disorders

Study Type: Observational
Start Date: April 4, 1995
Location: Bethesda, Maryland
Eligibility: Females, Ages 18–50, Accepts Healthy Volunteers

Determine whether postpartum depression is triggered by the abrupt withdrawal of estrogen and progesterone.

The appearance of mood and behavioral symptoms during pregnancy and the postpartum period has been extensively reported. While there has been much speculation about possible biologically based etiologies for postpartum disorders (PPD), none has ever been confirmed. Preliminary results from two related studies (protocols 90-M-0088, 92-M-0174) provide evidence that women with menstrual cycle related mood disorder, but not controls, experience mood disturbances during exogenous replacement of physiologic levels of gonadal steroids. The present protocol is designed to create a "scaled-down" hormonal milieu of pregnancy and the puerperium in order to determine whether women who have had a previous episode of postpartum major effective episode will experience differential mood and behavioral effects compared with controls and to determine whether it is the abrupt withdrawal of gonadal steroids or the prolonged exposure to gonadal steroids that is associated with mood symptoms. Supraphysiologic plasma levels of gonadal steroids will be established, maintained, and then rapidly reduced, simulating the hormonal events that occur during pregnancy and parturition. This will be accomplished by administering estradiol and progesterone to women who are pretreated with a gonadotropin releasing hormone (GnRH) agonist (Lupron). After eight weeks, administration of gonadal steroids will be stopped in one group of patients and controls, and a sudden decline in the plasma hormone levels will be precipitated. Another group will be maintained on supraphysiologic levels of estrogen and progesterone for an additional month. Outcome measures will include mood, behavioral and hormonal parameters as well as response to o-CRH (a separate protocol done in collaboration with NICHD).

A Treatment Study for Premenstrual Syndrome (PMS)

Study Type: Observational
Start Date: March 9, 1990
Location: Bethesda, Maryland
Eligibility: Females, Ages 18–50, Does Not Accept Healthy Volunteers

This study examines the effects of estrogen and progesterone on mood, the stress response, and brain function and behavior in women with premenstrual syndrome.

Previously this study has demonstrated leuprolide acetate (Lupron (Registered Trademark)) to be an effective treatment for PMS. The current purpose of this study is to evaluate how low levels of estrogen and progesterone (that occur during treatment with leuprolide acetate) compare to menstrual cycle levels of estrogen and progesterone (given during individual months of hormone add-back) on a variety of physiologic measures (brain imaging, stress testing, etc.) in women with PMS.

PMS is a condition characterized by changes in mood and behavior that occur during the second phase of the normal menstrual cycle (luteal phase). This study will investigate possible hormonal causes of PMS by temporarily stopping the menstrual cycle with leuprolide acetate and then giving, in sequence, the menstrual cycle hormones progesterone and estrogen. The results of these hormonal studies will be compared between women with PMS and healthy volunteers without PMS (see also protocol 92-M-0174).

At study entry, participants will undergo a physical examination. Blood, urine, and pregnancy tests will be performed. Cognitive functioning and stress response will be evaluated during the study along with brain imaging and genetic studies.

Perimenopause-Related Mood and Behavioral Disorders

Study Type: Observational
Start Date: July 12, 1988
Location: Bethesda, Maryland
Eligibility: Females, Ages 40–60, Accepts Healthy Volunteers

The purpose of this study is to investigate mood and behavior changes in the time period surrounding and including menopause. This is an observational study; volunteers who participate will not receive any new or experimental therapies.

Controversy exists regarding the relationship between estrogen and progesterone (gonadal steroid) changes and midlife-onset depression. This study will examine the role of gonadal steroids in perimenopausal mood and behavioral disorders.

Perimenopausal women with depression symptoms and a control group of healthy perimenopausal volunteers will be compared to identify correlates of the occurrence of depression. Participants with depressive symptoms may also participate in companion studies that will test the antidepressant efficacy of phytoestrogens and selective estrogen receptor modulators (SERMS).

A group of younger pre-perimenopausal women with normal menstrual cycle functioning will be followed through menopause in an effort to confirm the association of depression onset with changes in reproductive endocrine functioning....

Study of Premenstrual Syndrome and Premenstrual Dysphoria

Study Type: Observational
Start Date: August 24, 1981
Location: Bethesda, Maryland
Eligibility: Females, Ages 18–50, Accepts Healthy Volunteers

The purpose of this study is to identify and describe the symptoms of premenstrual syndrome (PMS).

Women who experience PMS symptoms will complete clinical interviews, self-rating scales, and evaluations of mood and endocrine function. A subgroup of women with severe PMS (Premenstrual Dysphoric Disorder or PMDD) will be offered additional research studies that focus on: 1) identifying the endocrine changes that may be responsible for changes in mood and behavior during the premenstrual period, 2) evaluating treatments for PMS symptoms, and/or 3) identifying genetic factors in women with and without PMS. Women with recurrent brief depression will also be recruited to serve as a comparison group.

Evaluation of the Genetics of Bipolar Disorder

Study Type: Observational
Start Date: August 4, 1980
Location: Bethesda, Maryland
Eligibility: Ages 18–85, Does Not Accept Healthy Volunteers

This study looks to identify genes that may affect a person's chances of developing bipolar disorder (BP) and related conditions.