Skip to content

COVID-19 is an emerging, rapidly evolving situation.

Get the latest public health information from CDC:
Get the latest research information from NIH:
Get the latest shareable resources on coping with COVID-19 from NIMH:


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

Depression — also known as major depressive disorder or clinical depression — is a common but serious mood disorder that can interfere with how people feel, think, and handle daily activities, such as sleeping, eating, or working. Although sadness can be a symptom of depression, it does not characterize the disorder. Symptoms of depression include sad or anxious mood, feelings of hopelessness or guilt, loss of interest in previous hobbies or activities, decreased energy, difficulty concentrating or sleeping, changes in appetite or weight, and persistent physical symptoms. People with depression experience symptoms nearly every day for at least two weeks. Learn more about depression.

Join A Study

For opportunities to participate in NIMH research on the NIH campus, visit the clinical research website. Travel and lodging assistance may be available.

Featured Studies

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

Mental Health Impact of COVID-19 Pandemic on NIMH Research Participants and Volunteers

Study Type: Observational
Start Date: September 24, 2020
Location: Bethesda, Maryland
Eligibility: Ages 18 and Older, Accepts Healthy Volunteers


The COVID-19 outbreak has caused many changes to people s normal social patterns. The respiratory illness has been the major focus of public health efforts. But most experts also agree that government and public health mandates to slow the spread of the illness, such as social distancing, have a significant effect on people s mental health. Environmental stressors, such as constraints on activities, social contact, and access to resources, take a toll. Researchers want to learn how stressors related to COVID-19 affect mental health over time.

Objective: To learn the relationship between stressors related to COVID-19 and self-rated measures of mental health symptoms and distress among a range of people.


English-speaking adults ages 18 and older


This study will be conducted online.

Participants will give their first and last name and email address. They will indicate if they have ever been in an NIH research study. They will get a username and password.

Every 2 weeks for up to 6 months, participants will complete online study surveys. They will get email reminders. Some surveys will be repeated. At the end of the study, they will complete a set of end-of-study surveys.

The surveys will ask about the following:

Age, sex, race, and other sociodemographic data

Mental and medical illness history and treatment

Family medical history

Mobility, self-care, and life activities

Behaviors related to alcohol and substance use disorder

Mental illness symptoms

Psychological distress

Stressors caused by the COVID-19 pandemic.

Participants will get links to mental health resources, such as hotlines. They will also get guidance on steps to take to seek care or support.

Study website:

Title: Safety and Feasibility of Individualized Low Amplitude Seizure Therapy (iLAST)

Study Type: Interventional
Start Date: September 24, 2020
Location: Bethesda, Maryland
Eligibility: Ages 22–70, Does Not Accept Healthy Volunteers


Electroconvulsive therapy (ECT) is used to treat people with severe depression. During ECT, the brain is given electric pulses that cause a seizure. Although it is effective, it can cause side effects, including memory loss. Researchers want to study a new way to give ECT called iLAST.


To see if iLAST is safe and feasible in treating depression.


People ages 22 70 years old who have major depressive disorder and are eligible for ECT


Participants will be screened under protocol 01-M-0254. This includes:

Medical and psychiatric history and exam

Blood and urine tests

Participants will be inpatients at the Clinical Center. They study has 3 phases and will last up to 20 weeks.

Phase I will last 1 week. It includes:

MRI: Participants will lie in a scanner that takes pictures of the body

MEG: A cone over the participant s head will record brain activity.

TMS: A wire coil placed on the participant s scalp will produce an electrical current to affect brain activity.

SEP: An electrode on the participant s wrist will give a small electrical shock to test nerve function.

Phase II will last 2 and a half weeks. It includes:

Seven sessions of iLAST under general anesthesia. Participants may also get standard ECT.

EEG: A small electrode placed on the participant s scalp will record brain waves.

Interviews about mood, symptoms, and side effects. Participants facial expressions may be video recorded.


Phase III will last at least 1 week. It will include:





Standard ECT if needed. Participants will have sessions every other day, 3 times a week.

Sponsoring Institution: National Institute of Mental Health


Trial to Test Effectiveness of Depression Intervention for Mistreated Older Adults

Study Type: Interventional
Start Date: July 15, 2020
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 50 subjects that will participate in the study for approximately 12 weeks.

Association of Mood With Risk for Atherosclerosis

Study Type: Observational [Patient Registry]
Start Date: March 11, 2020
Location: Baltimore, Maryland
Eligibility: Ages N/A–22,

The investigators will aim to determine the association of mood disorders (MDO) with preclinical and clinical cardiovascular (CVD) risk factors among children.

The investigators will also aim to identify traditional and non traditional predictors of CVD risk among children with MDO.

PEERS Using Peer Mentors to Deliver Depression Care

Study Type: Interventional
Start Date: February 17, 2020
Location: Baltimore, Maryland
Eligibility: Ages 50 and Older, Accepts Healthy Volunteers

Fifteen to twenty percent of older Americans (6 to 8 million people) suffer from depression but more than one-half do not receive any services, a burden disproportionately shared by low-income and minority older adults who receive few or no services. The investigators propose to test a community-based peer model of depression care called PEERS (a peer support program) that provides self-care support for minority and low-income older adults.

IntelliCare in College Students - Implementation (ICCS-I)

Study Type: Interventional
Start Date: February 5, 2020
Location: Chicago, Illinois
Eligibility: Ages 18 and Older, Accepts Healthy Volunteers

This study is a hybrid effectiveness-implementation trial of the smartphone student stress-management app IntelliCare for college students. This intervention will be tested with University of Illinois at Chicago (UIC) and Northern Illinois University (NIU) students. During the study, participants will complete measures of depressive and anxious symptoms, as well as measures of mental health literacy, within the app.

Engaging Black Youth in Depression and Suicide Prevention Treatment Within Urban Schools

Study Type: Interventional
Start Date: January 31, 2020
Location: New York, New York
Eligibility: Ages 12–18, Accepts Healthy Volunteers

Completing evidence-based treatments for depression has been shown to be particularly problematic for Black adolescents. If Black adolescents' depression treatment needs are to be met, the engagement challenges and the factors that lessen the success of treatment in the "real world" must be addressed. The investigators will examine the effectiveness of the Making Connections Intervention (MCI) and investigate key mediators of both engagement and response to treatment for depression. The MCI is a 1-2 session, evidence-based intervention designed to improve engagement, perceived relevance, and treatment satisfaction among depressed, Black adolescents. The study also uses tailored outreach strategies for adolescents and parents by including innovative digital content such as a web page/app along with other digital products.

This study will address an important public health issue: How best to connect Black adolescents with depression to treatment in clinically meaningful ways, and how best to deliver evidence-based treatment to them through school-based services.

Theta Burst Stimulation in Young Adults With Depression

Study Type: Interventional
Start Date: January 31, 2020
Location: Pittsburgh, Pennsylvania
Eligibility: Ages 18–25, Does Not Accept Healthy Volunteers

For the proposed 2-year study, the investigators will conduct a within-subject, counterbalanced investigation using functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) to examine the acute effects of theta-burst stimulation (TBS) on function in dorsomedial prefrontal cortex (dmPFC) in 35 young adults with depression (18-25 years, 50% female).

Mechanism of Action Underlying Ketamine s Antidepressant Effects: The AMPA Throughput Theory in Patients With Treatment-Resistant Major Depression

Study Type: Interventional
Start Date: January 21, 2020
Location: Bethesda, Maryland
Eligibility: Ages 18–70, Does Not Accept Healthy Volunteers


Most drugs that treat mood disorders take a long time to work. Ketamine works within hours. A dose can last for a week or more. Certain receptors in the brain might help ketamine work. A drug that blocks these receptors might affect how it works.


To see if the antidepressant response of ketamine is linked to AMPA receptors.


Adults ages 18-70 with major depression disorder without psychotic features


Participants will be screened under protocol 01-M-0254. They will have blood tests and a physical exam.

Participants will stay at the NIH Clinical Center for 5 weeks.

Phase 1 lasts 4 weeks. For 2 weeks, participants will taper off their psychiatric medicine. Then they will have the following tests:

- Blood draws

- Psychological tests

- MRI: Participants will lie in a machine that takes pictures of their brain.

- MEG: Participants will lie down and do tasks. A cone lowered on their head will record brain activity.

- Optional sleep tests: Electrodes on the scalp and body and belts around the body will monitor participants while they sleep.

- Optional TMS: Participants will do tasks while a wire coil is held on their scalp. An electrical current will pass through the coil that affects brain activity.

For phase 2, on day 0 participants will take the study drug or a placebo orally. While having a MEG, they will get ketamine infused into a vein in one arm while blood is drawn from a vein in the other arm. On day 1, participants will again take the study drug or a placebo orally. On days 3-7, they will repeat many of the phase 1 tests. Days 8 and 9 are optional and include an open label ketamine treatment and many of the phase 1 tests.

Characterizing the Neural Substrates of Irritability in Women: an Experimental Neuroendocrine Model

Study Type: Interventional
Start Date: January 2, 2020
Location: Chapel Hill, North Carolina
Eligibility: Females, Ages 22–45, Accepts Healthy Volunteers

The proposed study involves experimentally manipulating reproductive hormones in nonpregnant, euthymic women to create a scaled down version of the changes that occur during pregnancy and the postpartum period. This endocrine manipulation paradigm, which the investigators have shown provokes irritability in past studies, will be used to examine the neurocircuitry underlying irritability under baseline and hormone challenge conditions among women who are hormone sensitive (HS+; n=15) and non-hormone sensitive (HS-; n=15). The long-term goal of this research is to advance understanding of the neural systems underlying both the triggering of and susceptibility to irritability in women. The objective of the current project is to examine whether HS+ show differences in the behavioral activation system relative to HS- under baseline and hormone challenge conditions using functional magnetic resonance imaging (fMRI) and behavioral tests.

The Parenting With Depression Study

Study Type: Interventional
Start Date: December 17, 2019
Location: Philadelphia, Pennsylvania
Eligibility: Females, Ages 18 and Older, Does Not Accept Healthy Volunteers

The purpose of this study is to determine whether a social media-based parenting program can improve responsive parenting among mothers with Postpartum depression (PPD) symptoms. Participants will be randomized to receive the parenting program plus online depression treatment or online depression treatment alone to assess target engagement. Our overall objective for this application is to study whether this program combined with online depression treatment leads to more responsive parenting (target) and signals improved child language, socioemotional and cognitive development (outcomes) compared to depression treatment alone.

Adaptation of the Friendship Bench Intervention for HIV-infected Perinatal Women in Lilongwe

Study Type: Interventional
Start Date: December 10, 2019
Locations: Lilongwe, Lilogwe, Malawi; Lilongwe, Malawi
Eligibility: Females, Ages 18 and Older, Does Not Accept Healthy Volunteers

In many sub-Saharan African countries, the scale-up of lifelong antiretroviral treatment (ART) to all pregnant and breastfeeding women under Option B+ has the potential to radically improve maternal health and reduce mother-to-child HIV transmission. However, loss to HIV care after delivery has emerged as an important threat to the hoped-for impact of Option B+. Evidence suggests that one important contributor to postpartum loss to HIV care is perinatal depression (PND). In non-pregnant HIV-infected populations, depression has been linked to poor ART adherence, reduced engagement in care, and ultimately worse HIV clinical outcomes. Thus, interventions that integrate PND treatment with targeted support for HIV care retention are critical to the success of Option B+.

The Friendship Bench is an evidence-based depression counseling intervention delivered by trained, supervised lay health workers. It is proven to reduce depression in the general population in low-resource settings, but has not been adapted to address PND, or enhanced to support engagement in HIV care. The Friendship Bench offers an ideal framework for integrating retention support into a proven depression treatment model. Our long-term goal is to adapt, test, and scale up resource-appropriate interventions to reduce PND and improve engagement in HIV care. The objective of this proposal is to lay the groundwork for an effectiveness trial by adapting the Friendship Bench intervention to address PND and support engagement in care among perinatal HIV-infected women and assessing the feasibility, acceptability, and fidelity of the adapted intervention in Lilongwe, Malawi. In-depth perspectives on PND and its role in engagement in care will be gathered from HIV-infected women with PND, healthcare providers, clinic directors, and Ministry of Health officials using qualitative interviews and focus groups. This formative research will be used to develop an intervention protocol adapted to the unique needs of HIV-infected women during the perinatal period (Adapted Friendship Bench) and further enhanced to support engagement in HIV care (Enhanced Friendship Bench). The Adapted and Enhanced Friendship Bench interventions will be compared to enhanced standard care in a 3-arm pilot study. Feasibility, acceptability, and fidelity will be assessed at 6 months postpartum, along with the interventions' preliminary effectiveness across several mental health and engagement in HIV care measures.

Adolescent Attention to Emotion Study

Study Type: Interventional
Start Date: October 16, 2019
Location: Pittsburgh, Pennsylvania
Eligibility: Females, Ages 13–15, Accepts Healthy Volunteers

Rates of depression increase rapidly during adolescence, especially for girls, and, thus, research is needed to spur the development of novel interventions to prevent adolescent depression. This project seeks to determine if a novel visuocortical probe of affect-biased attention (i.e., steady-state visual evoked potentials derived from EEG) can 1) be used to prospectively predict depression using a multi-wave repeated measures design and 2) modify affect-biased attention and buffer subsequent mood reactivity using real time neurofeedback. This work could ultimately lead to improved identification of adolescents who are at high risk for depression and directly inform the development of mechanistic treatment targets to be used in personalized intervention prescriptions for high-risk youth.

A Longitudinal Study of Inflammatory Pathways in Depression

Study Type: Observational
Start Date: October 1, 2019
Location: Grand Rapids, Michigan
Eligibility: Ages 18 and Older, Does Not Accept Healthy Volunteers

Suicide accounts for at least 1 million deaths globally each year. This is likely a significant underestimate, because suicide is under-reported in many countries. In the US, over 42,000 people die from suicide annually. Despite increased focus on identification and treatment, the rate of suicide has increased steadily over the past 15 years.

Our project aims both to improve our understanding of factors that increase the risk for suicide by comparing blood biomarkers associated with inflammation in patients with depression without suicidal behavior and patients with depression and suicidal behavior. The 160 individuals in this study will be followed with psychiatric assessments and blood samples at repeated time points over one year.

Low Intensity Family Support for Refugees in an LMIC

Study Type: Interventional
Start Date: August 16, 2019
Location: Istanbul, Turkey
Eligibility: Ages 12–55, Accepts Healthy Volunteers

The rapidly growing scale of humanitarian crises requires new response capabilities geared towards addressing populations with prolonged high vulnerability to mental health consequences and little to no access to mental health, health, and social resources. This R21 develops and pilot tests a novel model for helping urban refugee families in LMICs with little to no access to evidence-based mental health services, by delivering a transdiagnostic family intervention for common mental disorders in health sector and non-health sector settings. The project is located in Istanbul, Turkey. Aim 1 forms a Family Support Design Team (FSDT) to adopt the PM+ and CAFES manuals into a family support (FS) intervention for use with refugee families by lay providers in community sites and nurses in clinical sites using a four-session multiple family group format. Aim 2 pilots FS with families in community and clinical sites, and then through observations and qualitative interviews, assesses FS's feasibility, fidelity, the impact of context and local capacity, the experiences of intervention delivery, and practitioner and organizational perspectives on scale up. Aim 3 conducts pre, immediate post, and 3-month post assessments of the refugee families who received FS through all the sites, to demonstrate the kind of pre-post changes that have been reported for comparable interventions and to determine key parameters of interest with sufficient accuracy and precision. This exploratory investigation, conducted with the support and advice of the World Health Organization, will strengthen the research capabilities of the academic and community partners in Istanbul and will develop new evidence-based mental health services for refugees in Turkey and other LMICs, as well as for refugees and migrants in low resource communities in the United States.

BRITEPath, Component 3 of iCHART (Integrated Care to Help At-Risk Teens)

Study Type: Interventional
Start Date: August 6, 2019
Locations: Pittsburgh, Pennsylvania; Seattle, Washington
Eligibility: Ages 12–26, Does Not Accept Healthy Volunteers

BRITEPath (BP) aims to support co-located mental health clinicians in the development of a high quality, effective, and personalized safety plan for referred patients who screen positive for depression and/or suicidal ideation.

BRITEPath utilizes BRITE, a safety planning and emotion regulation app that is loaded on the patient's smart phone and has previously been shown to be well accepted and to reduce suicide attempts compared to usual care in psychiatric inpatients (HR = 0.49). To support mental health clinicians in the development of effective safety plans, study investigators will develop Guide2Brite (G2B), which provides step-by-step instructions for the mental health clinician on how to populate BRITE onto the patient's smartphone and BRITEBoard, a clinician dashboard that tracks patient symptoms, app use, and rating on helpfulness of different interventions assessed through BRITE.

Development of a Novel Transdiagnostic Intervention for Anhedonia - R33 Phase

Study Type: Interventional
Start Date: August 1, 2019
Location: Chapel Hill, North Carolina
Eligibility: Ages 18–50, Does Not Accept Healthy Volunteers

The overall goal of this project is to develop a novel transdiagnostic treatment for anhedonia, called Behavioral Activation Treatment for Anhedonia (BATA), using ultra-high field functional neuroimaging. There is a critical need for a validated treatment that specifically targets anhedonia, and this project will evaluate the effects of this new treatment on anhedonia and will establish how this treatment impacts brain systems that mediate reward processing, clinical symptoms of anhedonia, functional outcomes, and behavioral indices of reward processing. This work will also identify brain targets by which future novel anhedonia treatment may be evaluated.

Task Shifting to Treat Depression and HIV Medication Nonadherence in Low Resource Settings

Study Type: Interventional
Start Date: July 12, 2019
Location: Marondera, Mashonaland East, Zimbabwe
Eligibility: Ages 18 and Older, Does Not Accept Healthy Volunteers

A hybrid effectiveness-efficacy trial to evaluate a stepped care task shifted intervention to treat depression and HIV medication nonadherence in low resource settings in rural Zimbabwe.

Text2Connect, Component 2 of iCHART (Integrated Care to Help At-Risk Teens)

Study Type: Interventional
Start Date: May 28, 2019
Locations: McMurray, Pennsylvania; Pittsburgh, Pennsylvania
Eligibility: Ages 12–26, Does Not Accept Healthy Volunteers

This study proposes to develop and examine a personalized, text-based intervention designed to improve engagement with mental health (MH) treatment.

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: May 23, 2019
Location: Bethesda, Maryland
Eligibility: Females, Ages 45–65, Does Not Accept Healthy Volunteers


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.


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


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


-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.

Mechanisms of Rumination Change in Adolescent Depression

Study Type: Interventional
Start Date: May 1, 2019
Location: Salt Lake City, Utah
Eligibility: Ages 14–17, Does Not Accept Healthy Volunteers

This study will evaluate whether a newer treatment, rumination-focused cognitive behavioral treatment, which includes mindfulness and can be used to reduce ruminative habits, change ways in which key brain regions interact with each other (e.g.., often called connectivity), and whether these changes in habits and brain connectivity can reduce the risk for recurrence of depression in the next two years.

Translational Model of Anhedonia

Study Type: Interventional
Start Date: April 1, 2019
Location: Albuquerque, New Mexico
Eligibility: Ages 18–55, Accepts Healthy Volunteers

The proposed research addresses a major mental health issue (anhedonia) with a novel computationally-inspired translational technique in both humans and mice. This approach greatly increases the likelihood that a positive animal model result will be successfully translated to humans. This research plan thus offers a novel way to address the NIMH's mission of defining mechanisms of complex behaviors.

CBT Enhanced With Social Cognitive Training

Study Type: Interventional
Start Date: February 11, 2019
Location: Nashville, Tennessee
Eligibility: Ages 12–17, Does Not Accept Healthy Volunteers

Depression in youth is a serious public health concern for which more personalized treatments are needed. This study will test the effect of an intervention aimed at enhancing depressed children's social cognitive capacities (e.g., ability to take another's perspective), thereby making treatment of depression in youth more efficient and effective. Participants in both the R61 (N=42) and R33 (N=82) will be youth between 12 and 17 years old currently experiencing a depressive disorder. Youth will be randomized to either an enhanced CBT intervention that teaches social cognitive skills, particularly social perspective taking and theory of mind as compared to CBT only. The primary target is improvement in the social cognitive skills at post treatment in the first trial (R61) and improvements in both social cognitive skills and depressive symptoms at post-treatment and at a 4-month follow-up (R33).

L-DOPA vs. Placebo for Depression and Psychomotor Slowing in Older Adults

Study Type: Interventional
Start Date: January 9, 2019
Location: New York, New York
Eligibility: Ages 60 and Older, Does Not Accept Healthy Volunteers

Individuals with Late Life Depression (LLD) often have cognitive problems, particularly problems with memory, attention, and problem solving, all of which contribute to antidepressant non-response. Our group and others have shown that decreased thinking speed is the central cause of functional problems in patients with LLD. Similarly, decreased walking speed is associated with depression and carries additional risk for falls, hospitalization, and death. Available evidence suggests that declining functionality in the brain's dopamine system contributes to age-related cognitive and motor slowing. The central hypothesis of this study is that by enhancing dopamine functioning in the brain and improving cognitive and motor slowing, administration of carbidopa/levodopa (L-DOPA) will improve depressive symptoms in older adults.

Adapting Behavioral Activation to Technology Platform

Study Type: Interventional
Start Date: January 1, 2019
Location: Seattle, Washington
Eligibility: Ages 13–17, Does Not Accept Healthy Volunteers

This project aims to use an asynchronous remote communities (ARC) approach both to discover the design requirements for adapting Behavioral Activation (BA) to ARC as well as design/build an ARC platform for administering BA. The investigators will test the feasibility of our approach in a small feasibility observational study with clinicians and adolescents.

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.

Technology Enhanced Family Treatment

Study Type: Interventional
Start Date: November 15, 2018
Location: Los Angeles, California
Eligibility: Ages 13–19, Does Not Accept Healthy Volunteers

The investigators propose to enhance the scalability of family-focused therapy (FFT), a 12-session evidence-based therapy for youth at high risk for mood disorders, through augmentation with a novel mobile phone application called MyCoachConnect (MCC). In adolescents with mood instability who have a parent with bipolar or major depressive disorder, clinicians in community clinics will conduct FFT sessions (consisting of psychoeducation and family skills training) supplemented by weekly MCC "real time" assessments of moods and family relationships; based on results of these assessments and the family's progress in treatment, clinicians will then push personalized informational and coaching alerts regarding the practice of communication and problem-solving skills. The investigators hypothesize that the augmented version of FFT (FFT-MCC) will be more effective than FFT without coaching/informational alerts in altering treatment targets and in stabilizing youths' mood symptoms and quality of life.

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.

School-Based Depression Prevention for Adolescents With ADHD

Study Type: Interventional
Start Date: August 7, 2018
Location: College Park, Maryland
Eligibility: Ages 14–18, Does Not Accept Healthy Volunteers

The purpose of this study is to develop a modified behavioral activation program in adolescents with ADHD to be implemented by school mental health providers in an urban, low-income school district. Subsequently we will examine its effectiveness in reducing depressive symptoms and improving emotion regulation and reward responsivity, compared to usual care.

Confirmatory Efficacy and Safety Trial of Magnetic Seizure Therapy for Depression

Study Type: Interventional
Start Date: June 26, 2018
Location: Dallas, Texas
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


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.


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


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.


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.

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).

Stabilizing Behavioral Rhythms to Improve Mental Health

Study Type: Interventional
Start Date: March 1, 2018
Location: Salt Lake City, Utah
Eligibility: Ages 18–65, Does Not Accept Healthy Volunteers

In order to assess the efficacy of the Rhythm Stabilization component of HealthRhythms' product, investigators will recruit 128 outpatients between the ages of 18 and 65, presenting to the University of Utah Department of Psychiatry outpatient clinics with a current mood and/or anxiety disorder. Sixty-four of these individuals will be randomly allocated to receive the full HealthRhythms package (Rhythm Sensing, Rhythm Trending, and Rhythm Stabilization) on their smartphones, while 64 will be asked to consent to Rhythm Sensing only. Participants in both arms will receive treatment as usual (TAU) for their mood and/or anxiety disorders, as typically provided at the University of Utah clinics. The duration of the study will be 16 weeks.

The primary outcome measures of the RCT will be the PROMIS Depression, the PROMIS Anxiety and the PROMIS Sleep Disturbance computerized adaptive testing (CAT) measures. The investigators hypothesize that those receiving the full package will demonstrate lower levels of depression, anxiety and sleep disturbance. In addition, investigators will explore the relationship between sensed rhythm stability and scores on patient-reported outcome measures of mood, anxiety and sleep disturbance (PROMIS). The investigators hypothesize that positive changes in the PROMIS measures will be mediated by positive changes in rhythm stability.

The primary outcome analyses will be based on random regression models, while the mediation analyses will follow the approach described by Helena Kraemer and colleagues.

An Adaptive Algorithm-Based Approach to Treatment for Adolescent Depression

Study Type: Interventional
Start Date: February 26, 2018
Location: Minneapolis, Minnesota
Eligibility: Ages 12–18, Does Not Accept Healthy Volunteers

The purpose of this study is to evaluate the effectiveness of two adaptive treatment strategies (ATSs) for adolescent depression. The ATSs include delivery of an evidence-based psychotherapy (interpersonal psychotherapy for depressed adolescents, IPT-A), systematic symptom monitoring, and an empirically-derived algorithm that specifies whether, when, and how to augment IPT-A. Two hundred depressed adolescents (age 12-18) will be recruited to participate in a 16-week sequential multiple assignment randomized trial conducted in outpatient community mental health clinics. Adolescents will be randomized to the IPT-A ATS condition or the community clinic's usual care (UC). Adolescents in the IPT-A ATS condition who are insufficient responders will be randomized a second time to the addition of a selective serotonin reuptake inhibitor (SSRI) or more intensive IPT-A (delivered twice per week). Research assessments will be administered at baseline and at weeks 4, 8, 12, 16, and 36.

Scaling Up Science-based Mental Health Interventions in Latin America

Study Type: Interventional
Start Date: February 13, 2018
Locations: Duitama, Boyaca, Colombia; Santa Rosa de Viterbo, Boyaca, Colombia; Guatavita, Cundinamarca, Colombia; Soacha, Cundinamarca, Colombia; Guayabal, Tolima, Colombia; 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.

Characterization and Treatment of Adolescent Depression

Study Type: Observational
Start Date: December 28, 2017
Location: Bethesda, Maryland
Eligibility: Ages 11–25, Accepts Healthy Volunteers


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


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


People ages 11 17 with major depressive disorder or subthreshold depression

Healthy volunteers ages 11 17


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

At the initial visit, participants will:

Perform tasks and be interviewed

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

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

Have brain and eye activity monitored

Do tasks in a virtual reality environment

Wear an activity monitor

Choose to have blood taken for research studies

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

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

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

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

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.

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.

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


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.


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.


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

Ketamine Metabolites Substudy: Healthy volunteers ages 18-65


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

Inflammation-Induced CNS Glutamate Changes in Depression

Study Type: Interventional
Start Date: May 15, 2017
Location: Atlanta, Georgia
Eligibility: Ages 21–65, Does Not Accept Healthy Volunteers

Increased inflammation has been implicated in the pathophysiology of a number of neuropsychiatric illnesses including mood disorders, which affect almost 30 million adults in the United States alone. One mechanism by which inflammation may alter behavior is through increasing brain glutamate, a neurotransmitter that in excess has been implicated in neuronal toxicity and resistance to conventional antidepressant therapy. The goal of the proposed research is to test the hypothesis that inflammation alters behavior through increasing glutamate in specific brain regions, ultimately leading to behavioral changes.

The proposed research is designed to determine the cause and effect relationship between inflammation and CNS glutamate as well as the relationship between CNS glutamate and specific symptoms. To accomplish these aims, investigators will administer a single infusion of either the tumor necrosis factor (TNF) antagonist infliximab or placebo (n=30 per group) to patients with high inflammation (CRP>3mg/L). A CRP>3mg/L was chosen because it is considered high inflammation according to guidelines by the American Heart Association. Moreover, a CRP>3mg/L is associated with significantly increased basal ganglia glutamate and with a clinical response to infliximab. Inflammatory biomarkers, basal ganglia glutamate as measured by MRS, and motivation and psychomotor activity will be assessed at baseline and days 1 and 3 and weeks 1 and 2 following infliximab or placebo administration.

Feasibility of Implementing a Mental Health Care Program and Home-based Training for Mothers of Children With Autism Spectrum Disorder in an Urban Population in Bangladesh

Study Type: Interventional
Start Date: April 1, 2017
Location: Dhaka, Bangladesh
Eligibility: Females, Ages 18–50, Does Not Accept Healthy Volunteers

Background (brief):

The global burden of depression accounts for 2.5% of global DALYs, and in South Asia the estimate is 13.3 % of DALYs per 100,000 populations. Mothers of children with Autism Spectrum Disorder (ASD) have reported higher level of depression than mothers of children with other developmental disorder and the prevalence of ASD is high in Asian countries. In Bangladesh 16% of adults suffer from depression and a recent study conducted in Bangladesh has documented a high prevalence of depression among mothers of children with ASD (45%). Mothers are the life time care givers of children with ASD, and a high burden of depression is likely negatively impact on the ability of the mothers to provide care to children at home. Mental health is not addressed in Bangladesh and there is scarcity of qualified providers.


The investigators propose to pilot the feasibility of a package intervention including implementation of mental health care and home based training program for the mothers of children with ASD integrated in the regular activities of the special schools that offer ASD care in Dhaka city in Bangladesh.


The study will be conducted in 2 selected special schools over 15 months. In the first stage, the investigators will set up the study in two schools and identify various stakeholders for qualitative assessment of the barriers of implementing the intervention at the institutional level, individual level, family level, provider level, policy maker level and at the level of the state. Research staff will identify mothers 18 years of age or older who has a child with ASD between 3 and 17 years of age enrolled in the school. Following consent, data collector will obtain data and assess current major depressive episode (MDE) of the eligible mothers following a standard diagnostic tool (SCID-I). All mothers diagnosed as having MDE will be invited to participate in the intervention (intervention mothers) and the investigators will assess the performances in children with ASD by applying ASD Diagnostic Check-list (ADCL).

In the second stage, investigators will implement interventions over 4-6 months, including (a) implementing mental health care services at the selected schools targeting the intervention mothers, and (b) organizing training sessions of the intervention mothers for supporting child care at home for enhancing child performances. Every month a psychiatrist will visit each school for providing necessary advice and treatment to the intervention mothers or suggest referral to hospital care, if necessary.

One special educator will be deployed at each school who will organize structured training sessions for educating the intervention mothers by using BCC materials developed and validated by icddr,b in the local setting. The special educators will conduct multiple group sessions including 5-8 mothers in each group for covering the 6 modules over 2 weeks time, and follow up intervention mothers at home every month for conducting refresher's training, documenting the need of additional training supports, and linking mother with an ASD expert for helping mothers taking a decision.

In stage 3, investigators will conduct post intervention qualitative survey with various stakeholders who would be involved with implementing the intervention and participated in the baseline qualitative survey. End line assessment will be conducted of current major depressive episode (MDE) among all mothers and assess the performance of the children of intervention mothers in order to assess the impact of the training at home.

Outcome measures/variables:

The primary outcome of the study is to assess the feasibility of institutionalizing the combined intervention of mental health care supports and the home based training program of the mothers who would be diagnosed as having major current major depressive episode. The primary outcome will be assessed by obtaining the perspectives of various stakeholders. The following parameters will be assessed for measuring feasibility of the proposed intervention.

Acceptability, Adaptability, Demands, Practicality, Implementation, Integration

The secondary outcomes will include estimating the impact of the combined interventions on the prevalence rate of maternal depression (MDE), individual performances of children, and cost of intervention. Adaptation of the proposed strategy, if feasible will help the mothers of children with ASD become skilled workforces for filling in the gap of the special educators in resource poor settings, and extension of these services to more children with ASD.

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. 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.

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.

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.

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.

Neurobiology of Suicide

Study Type: Interventional
Start Date: December 1, 2015
Location: Bethesda, Maryland
Eligibility: Ages 18–70, Accepts Healthy Volunteers


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.


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


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.


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.

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.

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

Study Type: Interventional
Start Date: April 20, 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.

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.

Ketamine Alcohol (in Treatment-Resistant Depression)

Study Type: Interventional
Start Date: April 23, 2014
Location: Iowa City, Iowa
Eligibility: Ages 21–65, Does Not Accept Healthy Volunteers

A single subanesthetic dose infusion of the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine has rapid and robust antidepressant effects in patients with treatment-refractory major depressive disorder (TRD). A family history of an alcohol use disorder (Family History Positive, FHP) is one of the strongest identified predictors of an improved antidepressant response to ketamine. Like ketamine, alcohol is a functional NMDA receptor antagonist. FHP is associated with differential response to both alcohol, e.g. decreased body sway and plasma cortisol, and ketamine, e.g. blunted psychotomimetic side effects. One of the primary mechanistic hypotheses for ketamine's antidepressant action is the acute intrasynaptic release of glutamate from major output neurons, e.g. cortical pyramidal cells. Preliminary clinical studies have demonstrated this acute glutamate "surge" in response to subanesthetic dose ketamine. Based on these findings, the investigators hypothesize that ketamine's enhanced antidepressant efficacy in FHP TRD subjects is, at least in part, attributable to increased glutamate release relative to TRD subjects without a family history of alcohol use disorder (Family History Negative, FHN). The investigators also hypothesize that alcohol similarly augments glutamate release in this bio- logically-enriched subgroup, which may be a more objective biomarker than family history status. To test these hypotheses, the investigators have designed a now two-site, open-label study of 21-65 year old medically and neurologically healthy, currently moderately-to-severely depressed TRD patients. In total, the investigators plan to recruit 25 FHP and 25 FHN TRD subjects. All subjects must not have a lifetime substance use disorder (except nicotine or caffeine), no lifetime history of an alcohol use disorder and socially drink. The experimental portion consists of two phases. The preliminary first phase is a medication taper (if needed) and psychotropic medication-free period. The experimental second phase comprises two pharmacokinetically-defined basal-bolus alcohol and one subanesthetic dose (0.5mg/kg x 40 minute) ketamine infusions. The first alcohol infusion will establish the pharmacokinetic profile for a subsequent alcohol infusion occurring during 7T-magnetic resonance imaging (MRI), both resting-state functional MRI (rs-fMRI) and magnetic resonance spectroscopy (MRS) to detect glutamate in the ventromedial prefrontal cortex/ventral anterior cingulate cortex (vmPFC/vACC). The ketamine infusion will also occur during 7T-MRI. The primary outcome measure is group mean change in Montgomery-Åsberg Depression Rating Scale (MADRS) score from pre-ketamine infusion (baseline) to one week post-infusion, where the investigators observed ketamine's greatest antidepressant effect in FHP TRD. Additional outcome measures are vmPFC/vACC glutamate change in response to ketamine and alcohol challenge based on family history status. In summary, this study will provide key mechanistic information on ketamine's improved antidepressant efficacy in a biologically-enriched subgroup. This will contribute to the systematic development of more efficacious, personalized treatments for major depression in an effort to reduce its enormous public health burden.

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.

Development of Magnetic Resonance Imaging Techniques for Studying Mood and Anxiety Disorders

Study Type: Observational
Start Date: December 6, 2006
Location: Bethesda, Maryland
Eligibility: Ages 18–65, Accepts Healthy Volunteers

This study is intended to help develop new MRI imaging techniques for studying mood and anxiety disorders. Researchers believe that depression and anxiety disorders may cause structural and functional changes in the brain. This study will optimize the way MRI scans are collected to look at brain structure and examine how the brain behaves while subjects perform particular tasks.

Healthy normal subjects between 18 and 50 years of age who have never had a major psychiatric disorder and who have no first-degree relatives with mood disorders may be eligible for this study. Candidates are screened by phone with questions about their psychiatric and medical history, current emotional state and sleep pattern, and family history of psychiatric disorders. Candidates who pass the preliminary screening then undergo additional screening interviews and laboratory tests.

Participants undergo magnetic resonance imaging (MRI) and neuropsychological testing, as follows:

" MRI scans: Subjects are asked to participate in an MRI study on one of several scanners to measure blood flow in the brain, concentrations of certain chemicals in the brain, or magnetic properties of the brain. MRI uses a strong magnet and radio waves to obtain pictures of the brain. The subject lies still on a narrow bed with a metal coil close to the head. For this study, subjects may be asked to wear a special coil on the neck to help measure blood flow. They may be asked to watch a screen presenting images or to do a task in which they respond to pictures or sounds and may be asked to return for additional scans.

" Neuropsychological testing: Subjects may undergo tests of cognitive performance. Often, people with mood disorders have subtle changes in performance on these tests that allow researchers to pinpoint where brain abnormalities occur. Before the tests can be used in patients, they must be validated by using healthy subjects. These tests are presented either orally, in written form, or on a computer.

Family Study of Affective and Anxiety Spectrum Disorders

Study Type: Observational
Start Date: May 21, 2004
Location: Bethesda, Maryland
Eligibility: Ages 7 and Older, 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: November 10, 2003
Location: Bethesda, Maryland
Eligibility: Ages N/A–29, 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: January 1, 2002
Location: Bethesda, Maryland
Eligibility: Ages 7–60, Does Not Accept 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.

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

Study Type: Interventional
Start Date: October 2, 2001
Location: Bethesda, Maryland
Eligibility: Ages 8–50, Accepts Healthy Volunteers

Objective: This protocol uses functional magnetic resonance imaging (fMRI) to examine neuro-cognitive correlates of pediatric and adult mood and anxiety disorders. The primary goal of the project is to document, in pediatric anxiety disorders and major depression, perturbations in brain systems mediating attention biases, fear conditioning, emotional memory, and response to various forms of motivational stimuli. As one secondary goal, the project measures the relationship between these factors and treatment response to either fluoxetine, a specific serotonin reuptake inhibitor (SSRI), cognitive behavioral therapy (CBT), or interpersonal psychotherapy (IPT). Another secondary goal examines similar associations in adults.

Study Population: A total of 2530 children, adolescents, and adults will be recruited. Most subjects will not be able to complete all procedures. We seek to comprehensively study 150 juveniles with only a current anxiety disorder, 60 juveniles with current major depression, 150 juveniles with no psychiatric disorder, 100 adults with major depression, 60 adults with an anxiety disorder, and 150 adults with no psychiatric disorder. To achieve this, we are recruiting 2530 individuals.

Design: Subjects will be tested using fMRI paradigms designed to examine brain regions engaged when processing motivationally salient stimuli, as assessed during attention, memory, social interaction, reward, and fear-conditioning paradigms. After these initial fMRI tests, subjects with depression or an anxiety disorder receive treatment. Treatment will comprise open treatment with either fluoxetine or CBT, augmented with computer-based attention retraining, delivered in a randomized-controlled design, with random assignment to either active or placebo attentiontraining regimens. Adolescent subjects then will be re-tested after eight-weeks using only the attention, memory, and conditioning paradigms.

Outcome Measures: Prior imaging studies note that tasks requiring attention modulation, emotional memory, social interchange, and fear conditioning engage brain regions previously implicated in adult mood and anxiety disorders. These regions include most consistently the amygdala and ventral prefrontal cortex. Moreover, imaging studies of reward function implicate the striatum and prefrontal cortex in adult mood disorders. As a result, we hypothesize that attention, memory, social interaction, reward, and conditioning paradigms will engage the amygdala, ventral prefrontal cortex and striatum in both psychiatrically healthy and impaired subjects. Moreover, we hypothesize that these healthy and psychiatrically impaired groups will differ in the degree of engagement.

Juvenile subjects also will be treated for eight-weeks, and a subset will be re-tested with fMRI. We predict that pre-treatment abnormalities in neural circuitry will predict response to treatment, such that increased amygdala and prefrontal activation will occur in individuals who show the strongest response to treatment. Moreover, we hypothesize that effective treatment will normalize abnormalities in attention and emotional memory, as manifest in fMRI.

Evaluation of Patients With Mood and Anxiety Disorders and Healthy Volunteers

Study Type: Observational
Start Date: February 2, 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.

Perimenopause-Related Mood and Behavioral Disorders

Study Type: Observational
Start Date: March 5, 1989
Location: Bethesda, Maryland
Eligibility: Females, Ages 40–65, 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.

Evaluation of the Genetics of Bipolar Disorder

Study Type: Observational
Start Date: June 30, 1982
Location: Bethesda, Maryland
Eligibility: Ages 18 and Older, Accepts Healthy Volunteers

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

Study of Premenstrual Syndrome and Premenstrual Dysphoria

Study Type: Observational
Start Date: March 7, 1982
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.