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Depression

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.

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Featured Studies

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

Levodopa and Exercise for Older Adults With Depression and Psychomotor Slowing

Study Type: Interventional
Start Date: August 15, 2021
Location: New York, New York
Eligibility: Ages 60–100, Does Not Accept Healthy Volunteers

In this new research study, 80 adults aged > 60 years with a significant depressive disorder and slowed processing and/or gait speed will be randomized to receive levodopa (L-DOPA; which the Candidate has previously shown to increase psychomotor speed and decrease depressive symptoms in older adults), aerobic exercise (itself an effective antidepressant treatment as monotherapy), or their combination in a 2x2 design incorporating placebo and a stretching/toning control. Participants will be evaluated before and after this 12-week duration study across cognitive domains, psychiatric symptoms, gait kinematics and mobility, and task-based magnetic resonance imaging (MRI) focused on effort-based decision making and reward processing. Data from this study will contribute toward the development of improved treatment and prevention strategies to maximize the functioning and active healthspan of older adults with neuropsychiatric disorders.

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

Study Type: Interventional
Start Date: August 5, 2021
Location: Bethesda, Maryland
Eligibility: Ages 22–70, Does Not Accept Healthy Volunteers

Background:

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.

Objective:

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

Eligibility:

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

Design:

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.

TMS

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

MRI

EEG

TMS

MEG

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

Sponsoring Institution: National Institute of Mental Health

...

PET Imaging of Cyclooxygenase in Participants With Major Depressive Disorder (MDD)

Study Type: Interventional
Start Date: July 20, 2021
Location: Bethesda, Maryland
Eligibility: Ages 18–70, Accepts Healthy Volunteers

Purpose: To determine whether COX-1 and COX-2 are detectable in the brains of individuals with MDD experiencing a major depressive episode (MDE).

Endpoints:

Primary Endpoint:

Group A - Calculation of COX-2 density from [11C]MC1 PET scans, using baseline scans and scans after blockade with celecoxib.

Group B - Calculation of the density of COX-1 using [11C]PS13 in healthy volunteers and depressed subjects.

Secondary Endpoints:

1. the relationship between peripheral markers of inflammation and COX binding

2. the relationship between clinical rating scales and COX binding

Study Design: Group A Sixteen (16) medication-free participants with MDD; Group B Three groups of 16 subjects each will be studied: 1) Medicated MDD, 2) Unmedicated MDD and 3) healthy volunteers. Participants may be male or female. They must be between 18 and 70 years old. Individuals may be recruited from anywhere but, for those participating in the outpatient study, most are expected to come from the Washington DC metropolitan area. MDD participants must be in good medical health and provide informed consent.

Data acquisition of [11C]MC1 and [11C]PS13:

1. Dynamic 3D PET brain scan on PET/CT.

2. One venous line for radioligand injection.

3. Arterial line for blood sampling.

4. Transmission (CT) scan will be performed to measure and correct for attenuation.

5. Injection of 20 mCi of [11C]MC1 or [11C]PS13.

6. Emission scans on PET/CT or PET scanner. Emission scan for about 90 min (possibly up to 2h). Frame information: 6 frames 30 sec each, 3 frames 1 min each, 2 frames 2 min each, and remaining frames of 5 min each.

7. Vital signs (blood pressure, pulse, and respiratory rate) and ECG (either 3 or 12 lead) will be recorded within three hours of tracer injection, in the middle, and after the PET scan.

8. We will take the two [11C]MC1 scans preferably in same day. They should be separated by at least 2.5 hours

Blood analysis in [11C]MC1 and [11C]PS13:

1. Measurement of whole blood, plasma activity, and metabolite levels in all phases: MIB/NIMH.

2. Measurement of whole blood activity by PET Department is not required in any phase.

Administration of celecoxib: In these scans, specific binding of [11C]MC1 to COX-2 in the brain will be verified by a pre-blocking study using celecoxib (600 mg PO). Participants will be encouraged to have a light meal prior to PET studies with blockade by celecoxib. After oral administration, the plasma concentration peaks at about two hours (Paulson et al. 2001). Thus, we will administer celecoxib about two hours before the second PET scan.

Safety monitoring by MIB/NIMH:

1. Pre-scan labs within 24 hours prior to injection: Urine pregnancy test (woman of child bearing potential), CBC, acute care panel (Na, K, Cl, CO2, creatinine, glucose, urea nitrogen), hepatic panel (alkaline phosphatase, ALT, AST, bilirubin total, and bilirubin direct), glucose, mineral panel (albumin, calcium, magnesium, phosphorus).

2. C-reactive protein (CRP) will be measured in the pre-PET blood sample to assess overall inflammatory status in periphery.

3. Data for safety monitoring will be recorded at three timepoints: no more than three hours before injection, about the middle of the PET scan, and after the PET scan. Recorded data included: blood pressure, pulse, respiratory rate, and EKG (either 3- or 12-lead).

4. Post-scan labs: CBC, acute care panel (Na, K, Cl, CO2, creatinine, glucose, urea nitrogen), hepatic panel (alkaline phosphatase, ALT, AST, bilirubin total, and bilirubin direct), glucose, mineral panel (albumin, calcium, magnesium, phosphorus).

5. Pregnancy Tests: For women of childbearing potential, urine pregnancy testing will be done within the 24 hours prior to any MRI or PET scan. If the pregnancy test is positive, PET and MRI will not be done, and the subject will be taken off the protocol.

6. Follow-up Procedures: Subjects will be contacted one to three business days after each PET scan to determine whether they have had any untoward sequelae.

A Wearable Morning Light Treatment for Postpartum Depression

Study Type: Interventional
Start Date: June 23, 2021
Location: Ann Arbor, Michigan
Eligibility: Females, Ages 18 and Older, Does Not Accept Healthy Volunteers

This study will test a consumer health light therapy device (Re-Timer) for women with postpartum depression to better understand how it affects mood and the body clock (also called the circadian clock).

Eligible participants will be enrolled and randomized after baseline assessments. In addition to using the Re-Timer light for 5 weeks participants will complete questionnaires at various timepoints, record sleep information, wear an actigraph watch, and provide saliva samples. Additionally, the sleep of the participants' infants will also be monitored using an ankle-worn device (actigraph) and sleep diary at certain time-points as this may influence the mother's mood/sleep, and in turn affect the results.

The hypotheses regarding the bright light versus the placebo dim light of the study are:

- morning bright light therapy will produce greater improvement from pre- to post-treatment on the Hamilton Rating Scale for Depression

- morning bright light therapy will lengthen the Phase angle difference (PAD) and this will mediate change in depression symptoms.

- morning bright light therapy will produce greater improvements on self-reported depression symptoms, excessive daytime sleepiness, maternal-infant bonding, social functioning, and sleep-related impairment from pre- to post-treatment.

Mobile Health Solution for Homework During CBT

Study Type: Interventional
Start Date: June 10, 2021
Location: Tampa, Florida
Eligibility: Ages 7–17, Does Not Accept Healthy Volunteers

The purpose of this study is to preliminarily evaluate a web-based app to improve provider implementation and patient engagement in homework (i.e., between-session practice of skills learned during therapy) during child mental health treatment by conducting a small-scale feasibility trial in community practice settings comparing Cognitive Behavioral Therapy (CBT) to CBT enhanced with the app.

Antidepressant Effects of TS-161 in Treatment-Resistant Depression

Study Type: Interventional
Start Date: June 10, 2021
Location: Bethesda, Maryland
Eligibility: Ages 18–65, Does Not Accept Healthy Volunteers

Background:

Major depressive disorder (MDD) is a common, chronic mental illness. It can take weeks to months for antidepressants to work. Researchers want to test a new drug that might act more rapidly.

Objective:

To see if TS-161 will improve symptoms of depression in people with MDD.

Eligibility:

Adults ages 18-65 with MDD without psychotic features.

Design:

Participants will be screened under a separate protocol. They will have blood tests. They will complete surveys about their symptoms.

Participants will have an inpatient visit at NIH. Participation may last 12-16 weeks.

During the first phase of the study, participants will be tapered off their psychiatric medicines. For 2 weeks they will have a drug-free period.

During Phase II participants will take TS-161 or placebo. They will take TS-161 for 3 weeks and placebo for 3 weeks. In between the 3-week time period, they will have 2-3 weeks where they will be drug free. Participants will also have the following tests during this time:

- Interviews

- Physical exams

- Psychological tests and surveys about their symptoms

- Blood draws and urine samples

- They may complete tests of mood and thinking

- MRI (Magnetic resonance imaging): Participants will lie in a machine that takes pictures of their brain.

- Functional MRIs: They will perform tasks displayed on a computer screen inside the MRI scanner

- MEG (magnetoencephalography): Participants will lie down and do tasks of memory, attention, and thinking. A cone lowered on their head will record brain activity.

- Electrocardiograms to record the heart s electrical activity. Electrodes will be placed on the skin....

Life Experiences in Adolescents and the Development of Skills

Study Type: Interventional
Start Date: May 19, 2021
Location: Pittsburgh, Pennsylvania
Eligibility: Ages 12–15, Does Not Accept Healthy Volunteers

The primary objective of this study is to assess acquisition and retention of a Cognitive Behavioral Therapy (CBT)-based "cognitive restructuring" skill, among young adolescents (12-15 years of age) with elevated depression symptoms and with population-level variability in lifetime exposure to adverse childhood experiences. This study uses a repeated-measures, longitudinal design to investigate associations between adversity exposure and learning-related cognitive control processes in the context of elevated depression (Aim 1). Adversity exposure and cognitive control will be examined as direct predictors of cognitive restructuring skill acquisition and skill retention over six-months; an indirect pathway from adversity to skill acquisition through cognitive control will also be examined (Aim 2). The study also includes exploration of key characteristics of adversity, namely the type (threat of harm versus deprivation of resources) and developmental timing of exposure, as distinct predictors of skill acquisition (exploratory Aim 3).

Improving Attentional and Cognitive Control in the Psychological Treatment of Intrusive Thoughts

Study Type: Interventional
Start Date: April 30, 2021
Location: Boston, Massachusetts
Eligibility: Ages 18–60, Does Not Accept Healthy Volunteers

The investigators are conducting this study to learn more about the cognitive and attentional processes among individuals with three types of repetitive negative thinking (RNT): mental rituals (as seen in obsessive compulsive disorder, OCD), worries (as seen in generalized anxiety disorder, GAD), and ruminations (as seen in major depressive disorder, MDD). Specifically, the investigators are studying whether psychological treatment can help people with RNT who have trouble stopping unwanted thoughts and shifting their attention.

A Pilot Randomized Trial of Video-based Family Therapy for Depressed Home Visited Mothers

Study Type: Interventional
Start Date: April 22, 2021
Location: Lebanon, New Hampshire
Eligibility: Ages 15 and Older, Does Not Accept Healthy Volunteers

Depressed mothers (pregnant and post-delivery) make up a significant portion of Maternal, Infant, and Early Childhood Home Visiting (MIECHV) clients. Home visited mothers often experience family conflict that precipitates or worsens their depressive symptoms. This study uses an effectiveness-implementation hybrid type 1 design with a pilot randomized trial to test the feasibility, acceptability, tolerability, safety, and preliminary effectiveness of an innovative family therapy intervention that uses technology to bypass barriers to increase access to treatment for this vulnerable population.

Stay Connected: Testing an Intervention to Combat COVID-19 Related Social Isolation Among Seattle-area Older Adults

Study Type: Interventional
Start Date: April 6, 2021
Location: Seattle, Washington
Eligibility: Ages 60 and Older, Does Not Accept Healthy Volunteers

This study will use the University of Washington's ALACRITY Center's (UWAC) Discover, Design, Build, & Test (DDBT) method to develop and test an intervention to address the MH health needs of older adults in senior housing who are forced to not only shelter-in-place but cannot have family or other visitors during this time. Older people (those over 60 years in age) are especially vulnerable and are more likely to have severe - even deadly - coronavirus infection than other age groups. These facts led to the need to have older adults socially isolate in order to protect their health; visits with family and friends are limited, and in senior housing (independent, supported and assisted care residences) have limited such visits by family to one person a day. This necessary practice of social distancing, while addressing an important public health crisis, unintentionally creates social isolation and loneliness, another deadly epidemic amongst the older population. Even before COVID-19, social isolation and loneliness was a prominent mental health and social problem in the aged, one that is associated with increases in other chronic conditions, dementia and suicide. Effective interventions for social isolation exist but are difficult to access and may not address all the concerns older adults have about this particular period of social isolation. The purpose of this proposed study is to deploy an adaptation of Behavioral Activation Therapy called Stay Connected to treat depression in older adults. The adaptation will allow activity directors and staff in these settings and senior centers to deliver the therapeutic elements of the intervention (behavioral activation) in the context of social distancing/shelter-in-place policies. Social workers in these settings will oversee the activity director and staff delivery of the intervention. The investigators are working with a variety of senior housing types (HUD certified and private systems) and senior centers in Skagit (rural) and King (urban) counties of WA so that the resulting intervention is not tied to economic levels or access to digital technology.

Study of a PST-Trained Voice-Enabled Artificial Intelligence Counselor (SPEAC) for Adults With Emotional Distress (Phase 1)

Study Type: Interventional
Start Date: April 5, 2021
Location: Chicago, Illinois
Eligibility: Ages 18 and Older, Does Not Accept Healthy Volunteers

In the phase 1 of the SPEAC project the specific aims are to: (1) establish the functionality, usability, and treatment fidelity of Lumen using iterative, user-centered design, development, and formative evaluation; and (2) demonstrate feasibility, acceptability, and target engagement in a 2-arm pilot RCT. The aim 1 focuses on developing a voice-enabled, artificial intelligence (AI) virtual agent, named Lumen, trained in Problem Solving Therapy (PST) via an iPad-based application. The development of Lumen will employ iterative user-centered design-evaluation cycles. After the functionality, usability and treatment fidelity of Lumen are established, in the aim 2, we will conduct a 2-arm randomized clinical trial (RCT, Study 1) to pilot test Lumen.

Cognitive Behavioral Therapy Following Esketamine for Major Depression and Suicidal Ideation for Relapse Prevention

Study Type: Interventional
Start Date: March 5, 2021
Location: New Haven, Connecticut
Eligibility: Ages 18–65, Does Not Accept Healthy Volunteers

This is a rater-blinded, randomized controlled trial. All patients will receive esketamine for treatment of Major Depression with Suicidal Ideation (MDSI). Subjects will be randomized (1:1) to receive CBT (computer-assisted) or TAU alone following esketamine.

Internet-delivered Cognitive Behavioral Treatment of Depression and Anxiety in Latin American College Students

Study Type: Interventional
Start Date: March 1, 2021
Locations: Medellín, Colombia; Mexico City, Mexico
Eligibility: Ages 18 and Older, Does Not Accept Healthy Volunteers

The aim is to evaluate short term and longer term treatment effects of internet-delivered cognitive behavioral therapy compared to treatment as usual for college students with anxiety and/or depression in low-middle income countries of Latin America.

Electroconvulsive Therapy Amplitude Titration

Study Type: Interventional
Start Date: March 1, 2021
Location: Albuquerque, New Mexico
Eligibility: Ages 50–80, Does Not Accept Healthy Volunteers

This study is focused on advancing ECT treatment for older adults with depressive disorders by refining neuromodulation stimulus parameters to improve efficacy and cognitive safety.

Impact of Transcutaneous Vagal Nerve Stimulation on Stress Response in Major Depression

Study Type: Interventional
Start Date: March 1, 2021
Location: Charlestown, Massachusetts
Eligibility: Ages 50–65, Does Not Accept Healthy Volunteers

This study will identify the sex-dependent impact of expiratory-gated transcutaneous vagus nerve stimulation (tVNS) on the modulation of the stress response circuitry and associated physiology in major depressive disorder (MDD). We will evaluate a sample of 80 adults with recurrent MDD randomized to receive active or sham expiratory-gated tVNS during a functional magnetic resonance imaging (fMRI) session, with simultaneous mood and physiological assessments. We hypothesize that expiratory-gated tVNS will effectively modulate, in a sex-dependent manner, specific brainstem-cortical pathways of the stress circuitry and attenuate physiological deficits in MDD.

MicroRNA Correlates of Childhood Maltreatment and Suicidality

Study Type: Observational
Start Date: February 26, 2021
Locations: Birmingham, Alabama; Huntsville, Alabama
Eligibility: Ages 18–60, Accepts Healthy Volunteers

This is a research study to find out if childhood trauma and stress are associated with depression or suicidal risk. The study will assess the effects of both short-term and long-term stress on biomarker (e.g. miRNA [MiRNA]) levels. miRNAs are a type of RNA (genetic material that is translated into protein) that are found in throughout the body and blood. They are called microRNA because their size is much smaller than typical RNA molecules. miRNAs are highly responsive to environment. This responsiveness is reflected in their expression in individuals who are affected by environment such as stress. The investigators are gathering genetic material, including DNA and RNA, from each participant. The RNA will be taken from the small vesicles and cells in the participant's blood and analyzed. The vesicles are small objects that occur normally in the blood and that contain RNA. This information may help us to understand the cause of mental illness and to improve medical and psychiatric care in the future. There will be 450 participants enrolled in this study.

Lay-Delivered Behavioral Activation in Senior Centers

Study Type: Interventional
Start Date: February 10, 2021
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 Behavioral Activation to be delivered by lay volunteers ("Do More, Feel Better"; DMFB). The focus of Behavioral Activation is to guide clients to reengage in daily pleasant and rewarding activities, and reduce depressive symptoms. If the investigators can show that the lay delivery model has positive impact in comparison to MSW-delivered Behavioral Activation, the investigators will have identified an effective intervention that can be used by a large untapped workforce of older adult volunteers across the nation.

1/2-Dopaminergic Dysfunction in Late-Life Depression (The D3 Study)

Study Type: Interventional
Start Date: February 10, 2021
Location: New York, New York
Eligibility: Ages 60 and Older, Accepts Healthy Volunteers

Growing evidence suggests that dopamine contributes to key cognitive, emotional, and motor functions across the lifespan. In Late-Life Depression (LLD), dysfunction in these areas is common, predicts poor outcomes, and manifests as difficulties in motivation and effort along with cognitive and gait impairment. While studies of dopamine function in early and midlife depression primarily focus on individuals' ability to feel pleasure and respond to rewards, they often exclude the cognitive and physical function domains relevant for older adults despite a recognized decline in dopamine function with normal aging. The objectives of this collaborative R01 proposal between Columbia University/New York State Psychiatric Institute and Vanderbilt University Medical Center are to: 1) characterize dopaminergic dysfunction in LLD across cognitive, emotional, and motor domains at several levels of analysis (cellular Positron Emission Tomography [PET], circuit Magnetic Resonance Imaging [MRI], and behavioral / self-report); and 2) examine the responsivity of dopamine-related circuits and behavior to stimulation with carbidopa/levodopa (L-DOPA).

Neuroinflammation and Modulating Factors in Depression and HIV

Study Type: Interventional
Start Date: February 1, 2021
Location: Kampala, Uganda
Eligibility: Ages 18–65, Does Not Accept Healthy Volunteers

Determine if depression, which persists after depression treatment at 26 weeks, is associated with increased innate inflammation in a prospective cohort of HIV-infected Ugandans receiving SSRIs in which group psychotherapy is initiated.

DTA (Dopaminergic Therapy for Anhedonia) Study

Study Type: Interventional
Start Date: January 29, 2021
Location: Atlanta, Georgia
Eligibility: Ages 25–55, Does Not Accept Healthy Volunteers

The purpose of this 6-week, double-blind, placebo-controlled, crossover study is to explore new treatment options for people with depression who have high inflammation and anhedonia. Thirty-five male and female participants with depression, between the ages of 25-55 years of age, will be randomized to two study tracks (A and B) to receive both placebo and three doses of L-DOPA, given in different orders. Increases or decreases in each dose will occur gradually over 6 weeks of the study. Participants will complete lab tests, medical and psychiatric assessments, neurocognitive testing and functional MRI (fMRI) scans as part of the study. The total length of participation is about 2 months.

Evaluation of a Crowd-Powered Web Platform for Depression and Anxiety

Study Type: Interventional
Start Date: January 14, 2021
Location: Irvine, California
Eligibility: Ages 18 and Older, Does Not Accept Healthy Volunteers

100 participants will be enrolled in a two-armed randomized controlled trial of the Accumulated Depression and Anxiety Plans and Treatments (ADAPT) platform which integrates internet Cognitive Behavioral Therapy (iCBT) to determine impact on symptoms of depression and anxiety. This trial will pilot the effectiveness of the ADAPT platform, and evaluate the extent to which the ADAPT platform engages putative targets of personal relevance, skills use, and skills mastery.

Phase 1 Evaluation of (2R,6R)-Hydroxynorketamine

Study Type: Interventional
Start Date: January 11, 2021
Location: Durham, North Carolina
Eligibility: Ages 18–65, Accepts Healthy Volunteers

A 6-cohort single ascending dose (SAD) study will be conducted in healthy volunteers utilizing a slow-infusion intravenous (IV) route of administration. Standard safety, pharmacokinetics (PK) and qEEG monitoring will be evaluated at all dose levels. Subsequently, a 3-cohort multiple ascending dose (MAD) study will be conducted. Doses will be administered on days 1, 4, 7, and 10. Standard safety parameters will be monitored, and PK will be evaluated at all dose levels.

Collaboration Leading to Addiction Treatment and Recovery From Other Stresses

Study Type: Interventional
Start Date: January 8, 2021
Locations: Albuquerque, New Mexico; Belen, New Mexico; Edgewood, New Mexico; Lordsburg, New Mexico; Los Lunas, New Mexico; Silver City, New Mexico
Eligibility: Ages 18 and Older, Does Not Accept Healthy Volunteers

Collaboration Leading to Addiction Treatment and Recovery from Other Stresses (CLARO) is a five-year project that tests whether delivering care using a collaborative model helps patients with both opioid use disorders and mental health disorders.

IM Ketamine vs Midazolam for Suicidal ER Patients

Study Type: Interventional
Start Date: January 2, 2021
Location: New York, New York
Eligibility: Ages 18–65, Does Not Accept Healthy Volunteers

Rising US suicide rates and the increased risk of suicide among persons who visit an emergency department (ED) for suicidality make the ED an important site for interventions to prevent suicide. There is no approved treatment for rapid relief of suicidal thoughts although clinical trials, including ours, show relief of suicidal thoughts within hours of treatment with inexpensive, generic, sub-anesthetic ketamine. We propose a clinical trial of intramuscular ketamine in depressed ED patients with high-risk suicidality, which if successful would support a novel, easy-to-use, scalable intervention for busy emergency clinicians to implement.

Transcranial Direct Current Stimulation (tDCS) Therapy in Major Depression

Study Type: Interventional
Start Date: December 1, 2020
Location: Los Angeles, California
Eligibility: Ages 18–65, 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 antidepressant. Investigators will address these questions in a two-part randomized double blind exploratory clinical trial. For this part of the study, investigators will determine relationships between target engagement and clinical outcomes (mood) and functional sub-constructs of cognitive control and emotion negativity bias, and whether imaging markers at baseline predict changes in antidepressant response.

One hundred people with depression (50 in each group) will be randomized to receive either HD-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 HD-tDCS in the MRI scanner, which will allow investigators 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.

Collaborative Care for Perinatal Depression Care in Vietnam

Study Type: Interventional
Start Date: December 1, 2020
Location: Cần Thơ, Vietnam
Eligibility: Females, Ages 16–45, Does Not Accept Healthy Volunteers

Depression is the most common medical disorder of pregnancy, and suicide, most frequently found in women with depression, is a major source of maternal mortality. Perinatal depression affects approximately 15% of women in pregnancy and the year postpartum and affects both women and their children, both medically and as a result of impairment in the ability to care for self and others. In low- and middle-income countries (LMICs) where food insecurity can be severe, growth stunting is seen among the infants of women with untreated depression. Fortunately, effective treatment of perinatal depression with antidepressant medications and evidence-based psychosocial interventions (such as collaborative care) mitigates these risks. Yet there are a range of obstacles within LMICs to the delivery of services for perinatal depression and maternal suicide prevention, including a lack of awareness of this disorder and related evidence-based treatments, stigma among patients and providers, scarcity of specialty mental health care providers, and the lack of health information technology supports for the longitudinal care of chronic illness.

Mechanisms of Emotion Regulation Underlying Successful CBT in Depression

Study Type: Interventional
Start Date: November 25, 2020
Location: New York, New York
Eligibility: Ages 18–65, Does Not Accept Healthy Volunteers

This research aims to elucidate mechanisms through which change occurs during cognitive behavior therapy (CBT) for depression. Assessing meta-cognitive processes of self-knowledge (top-down), electrophysiological and behavioral correlates of emotion processing (bottom-up), and their relation to treatment outcome will provide new insights into the mechanisms of emotion regulation deficits in depression. It will also contribute toward the clinical goal of identifying patients who may benefit most from CBT for unipolar depression.

Screening Wizard- Phase 2

Study Type: Interventional
Start Date: November 5, 2020
Location: Pittsburgh, Pennsylvania
Eligibility: Ages 12–26, Accepts Healthy Volunteers

Screening Wizard (SW). Primary Care Providers (PCPs) are often uncertain about how to best refer adolescents who screen positive for depression or suicidality. Screen-positive youth who are either not in treatment, or express dissatisfaction with current treatment will be consented by an on-site research assistant (RA). Participants will answer questions via adaptive screens developed in a previous NIMH study (MH100155) for suicidal risk, anxiety, and mania. These will address perceived barriers and preferences about treatment. Participants are then randomized into 1 of 3 groups: 1) Providing the symptoms scores report of results to their provider based on their Screening Wizard responses (Screening as Usual); 2) Providing the symptoms scores report and their responses to treatment preferences and barriers including treatment recommendations their provider might suggest (Screening Wizard 2.0); or 3) Providing the report with treatment recommendations to their provider and a website called SOVA or Supporting Our Valued Adolescent, that is aimed at addressing perceptions about mental health providing support to teens through peer interaction that social workers and doctors moderate on a 24 hour a day basis (Screening Wizard 2.0 + SOVA).

BRITEPath- Phase 2

Study Type: Interventional
Start Date: November 5, 2020
Locations: Detroit, Michigan; Hyde Park, New York; Moon, Pennsylvania; Pittsburgh, Pennsylvania; Wexford, 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.

Depression Prevention in Older Spousally-bereaved Adults

Study Type: Interventional
Start Date: October 20, 2020
Location: Pittsburgh, Pennsylvania
Eligibility: Ages 60 and Older, Does Not Accept Healthy Volunteers

Using an indicated prevention approach, investigators propose to enroll 150 spousally-bereaved adults aged 60 years and older in the first 6 months after spousal death who are at high risk for major depression disorder because of subthreshold symptoms of depression. A confirmatory efficacy trial will be conducted in which participants will be randomly assigned to (a) self-monitor sleep, meals, and physical activity for 12 weeks using digital monitoring plus motivational health coaching (WELL; n=75); or (b) enhanced usual care (EUC, usual care plus study assessments, n=75). Objective actigraphic measures of the 24-hour pattern of day and nighttime activity - known as the rest-activity rhythm - will be measured to evaluate circadian rhythms as a mediator of treatment outcomes. Participants will be assessed at baseline, months 1 & 2, post-intervention, and 3, 6,12, 18-months post-intervention. In addition, the investigators will include a subset of participants bereaved by COVID-19 (or suspected as bereaved by COVID-19). Participants in this subset will undergo the same research procedures as the main cohort. Participants in both the main cohort and subset determined to be fully eligible will be randomized into two groups with a total of: usual care (EUC;n=125) and WELL (WELL; n=125).

Social Reward and Its Effect on Brain Functions in Psychotherapies for Mid- and Late-Life Depression

Study Type: Interventional
Start Date: October 15, 2020
Location: New York, New York
Eligibility: Ages 50–85, Does Not Accept Healthy Volunteers

Abnormalities in the Positive Valence System (PVS) are associated with depressive symptoms and reduced behavioral activation in mid- and late-life. This study will investigate the engagement of the PVS during exposure to social rewards, part of a novel streamlined psychotherapy for mid- and late-life depression. Use of computational modeling will enable identification of neuroimaging and behavioral profiles associated with greater treatment response, and may guide future personalization of psychotherapy.

Text 2 Connect- Texting Intervention for Mental Health Treatment Utilization

Study Type: Interventional
Start Date: October 1, 2020
Locations: McMurray, Pennsylvania; Pittsburgh, Pennsylvania
Eligibility: Ages 18 and Older, Does Not Accept Healthy Volunteers

Text2Connect (T2C) proposes to test a text-based intervention designed to improve engagement with mental health treatment.

Bupropion Versus Escitalopram on Reward Circuitry and Motivational Deficits

Study Type: Interventional
Start Date: September 23, 2020
Location: Atlanta, Georgia
Eligibility: Ages 25–55, Does Not Accept Healthy Volunteers

This study is designed to determine whether bupropion (vs escitalopram) increases functional connectivity (FC) within reward-related neurocircuits and decreases motivational deficits in depressed patients with increased inflammation and anhedonia. Participants will be randomized to take bupropion extended release (XL) or escitalopram for 8 weeks.

A Systems-Level Intervention for Rural Adults With Depression

Study Type: Interventional
Start Date: September 20, 2020
Locations: Hillsdale, Michigan; Jonesville, Michigan
Eligibility: Ages 18 and Older, Does Not Accept Healthy Volunteers

This study aims to test the effectiveness of a computer-assisted cognitive behavioral therapy for depression among rural adults. The intervention, called Raising Our Spirits Together (ROST), was developed via a community-based participatory approach and will be delivered in small groups, facilitated by local pastors. Groups will be held virtually, or in-person at two churches in rural Michigan. Eighty-four individuals will be recruited from Hillsdale, Michigan, to test the effect of ROST on depressive symptoms, compared to an Enhanced Control Condition (ECC).

Unobtrusive Monitoring of Affective Symptoms and Cognition Using Keyboard Dynamics (UnMASCK)

Study Type: Observational
Start Date: September 17, 2020
Location: Chicago, Illinois
Eligibility: Ages 25–50, Accepts Healthy Volunteers

Mood disorders are associated with significant financial and health costs for the United States, partially due to cognitive problems in these patients that can worsen disease course and impair treatment response. This study proposes to use smartphone-based technology to monitor cognitive problems in patients with mood disorders by linking brain network changes with predicted worsening of mood symptoms. The proposed study will provide evidence for using smartphone-based passive sensing as a cost-effective way to predict illness course and treatment response.

Approach-Avoidance, Computational Framework for Predicting Behavioral Therapy Outcome (AAC-BeT)

Study Type: Interventional
Start Date: September 11, 2020
Location: Tulsa, Oklahoma
Eligibility: Ages 18–65, Does Not Accept Healthy Volunteers

Depression and anxiety disorders rank in the top ten causes of years lived with disability. Less than 50% of patients experiencing long-lasting improvements to current gold-standard treatments. Two gold-standard behavioral interventions include behavioral activation, focused on enhancing approach behavior towards meaningful activities, and exposure-based therapy, focused on decreasing avoidance and challenging negative expectations. While these interventions have divergent treatment targets, there is little knowledge to inform which strategies should be used in the frequent case of comorbid anxiety and depression. Approach-avoidance decision-making paradigms focus on assessing responses when faced with potential rewards and threats, tapping into processes important for both anxiety and depression as well as behavioral activation and exposure-based therapy.

For this study, investigators will recruit individuals reporting both anxiety and depression symptoms and randomize them to one of three different interventions: (1) behavioral activation, (2) exposure-based therapy, and a non-specific therapy approach (3) supportive therapy. Participants will complete clinical, self-report, behavioral, and functional magnetic resonance imaging (fMRI) assessments before and after therapy. Investigators will use a computational approach to model factors that may influence one's behavior during approach-avoidance decision-making, including drives to avoid threat versus approach reward and confidence versus uncertainty in one's decisions.

This project will accomplish the following aims (1) Determine how changes in brain and behavior responses during approach-avoidance conflict relate to changes in mental health symptoms with the different therapy approaches, (2) Determine the degree to which baseline brain and behavior responses during approach-avoidance conflict predict response to the different therapy approaches, above and beyond the influence of demographics and baseline symptom severity.

Results will enhance understanding of how different psychotherapy approaches (behavioral activation, exposure-based therapy) may impact brain responses and decisions when faces with potential reward versus threat and approach versus avoidance drives. In addition, results will have important implications concerning the potential for a more personalized approach to psychotherapy, enhancing knowledge of which types of therapy strategies may be most beneficial for which individuals.

Reaching and Engaging Depressed Senior Center Clients

Study Type: Interventional
Start Date: September 3, 2020
Location: White Plains, New York
Eligibility: Ages 55 and Older, Does Not Accept Healthy Volunteers

The purpose of this study is to test the feasibility of one type of therapy session, Virtual Augmented Engage (Engage-A). The research is being done because the researchers are trying to learn if these approaches could be used by therapists in the community social service agencies to treat older adults with depression. The research will also measure clinician satisfaction after training and supervision of utilization of Engage-A.

SMART-DAPPER: Leveraging the Depression And Primary-care Partnership for Effectiveness-implementation Research Project

Study Type: Interventional
Start Date: August 31, 2020
Location: Kisumu, Kenya
Eligibility: Ages 18 and Older, Does Not Accept Healthy Volunteers

Despite carrying the vast majority of the global mental disorder burden, 75% of adults with mental disorders in Low and Middle Income Countries have no access to services. This study will test strategies for integrating first and second line evidence-based depression and trauma-related disorder treatments with primary care services at a large public sector hospital and conduct robust cost and cost-benefit analyses of each treatment to produce a "menu" of cost-benefit options for personalized, integrated mental health care with corresponding effectiveness and implementation values.

Transcranial Near Infrared Radiation and Cerebral Blood Flow in Depression

Study Type: Interventional
Start Date: August 1, 2020
Locations: Charlestown, Massachusetts; New York, New York; Orangeburg, New York
Eligibility: Ages 18–65, Does Not Accept Healthy Volunteers

This study will compare the effect of three transcranial photobiomodulation (t-PBM) doses (high, middle, and low irradiance) to sham t-PBM on PFC CBF as assessed with fMRI (BOLD) in this multi-center, phase I, double-blinded, dose-ranging, controlled, crossover study of 30 subjects with MDD. All eligible participants will undergo four sessions of t-PBM during fMRI so that they experience irradiances of 50, 300 and 700 mW/cm2 as well as sham. The order of dose administration will be randomized and t-PBM will be administered with the LightForce® EXPi Deep Tissue Laser TherapyTM System, Transcranial PhotoBioModulation-1000 (tPBM-2.0).

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.

Models of Auditory Hallucination

Study Type: Interventional
Start Date: February 27, 2020
Location: New Haven, Connecticut
Eligibility: Ages 18–45, Does Not Accept Healthy Volunteers

The purpose of this study is to address the shortcoming in clinical hallucination research by causally manipulating the neural loci of conditioned hallucination task behavior in-person in patients with psychosis using transcranial magnetic stimulation (TMS), tracking the impact of this manipulation on the number of times participants with hallucinations report hearing tones that were not presented. With such a causal intervention, the veracity of this explanation of hallucinations will be either validated or disconfirmed. If validated, the task can be further developed as a biomarker for predicting the hallucination onset, guiding, developing or tracking the effects of treatments for hallucinations.

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.

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

Background:

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.

Objective:

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

Eligibility:

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

Design:

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.

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

Study Type: Interventional
Start Date: December 10, 2019
Location: 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: Detroit, Michigan; Hyde Park, New York; 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

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.

The Sub-Saharan Africa Regional Partnership for Mental Health Capacity Building

Study Type: Interventional
Start Date: May 9, 2019
Locations: Chilumba, Karonga, Malawi; Karonga, Malawi; Kasungu, Malawi; Lilongwe, Malawi; Machinga, Malawi; Mchinji, Malawi; Mulanje, Malawi; Phalombe, Malawi; Zomba, Malawi
Eligibility: Ages 18–65, Does Not Accept Healthy Volunteers

The investigators will conduct an implementation science research study that will compare two different implementation strategies to facilitate ongoing Ministry of Health efforts to scale up depression treatment within non-communicable diseases clinics, as well as assessing clinic-related factors that will influence uptake.

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.

Reward Function and Therapy for Late-Life Depression

Study Type: Interventional
Start Date: March 14, 2019
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).

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.

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.

Confirmatory Efficacy and Safety Trial of Magnetic Seizure Therapy for Depression

Study Type: Interventional
Start Date: June 26, 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.

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).

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.

A Behavioral Intervention for Depression and Chronic Pain in Primary Care

Study Type: Interventional
Start Date: February 1, 2018
Location: New York, New York
Eligibility: Ages 50 and Older, Does Not Accept Healthy Volunteers

Chronic pain and depression frequently co-exist in late and mid-life and contribute to increased disability, high health care costs, psychiatric comorbidity, and suicide. The investigators will recruit 60 adults from Weill Cornell Medical Associates primary care practices; participants will be randomized to either Relief (a 9 session behavioral intervention) or usual care/referral for mental health care. Research assessments are conducted with both groups at study entry (Baseline), 6, 9, and 12 weeks.

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: Observational
Start Date: December 28, 2017
Location: Bethesda, Maryland
Eligibility: Ages 11–25, 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 why some people become depressed whilst others don t. One possibility is that the way people process rewarding stimuli could be related to their risk for depression.

Objective:

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

Eligibility:

People ages 11 17 with major depressive disorder or subthreshold depression

Healthy volunteers ages 11 17

Design:

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

At the initial visit, participants will:

Perform tasks and be interviewed

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

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

Have brain and eye activity monitored

Do tasks in a virtual reality environment

Wear an activity monitor

Choose to have blood taken for research studies

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

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

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

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

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 16–29, 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 participants 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.

A Closed-loop Assessment and Treatment Platform for Unipolar Depression and Anxiety

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

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

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

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.

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.

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.

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.

Optimizing Outcomes of Treatment-Resistant Depression in Older Adults

Study Type: Interventional
Start Date: February 24, 2017
Locations: Los Angeles, California; Saint Louis, Missouri; New York, New York; Toronto, Ontario, Canada
Eligibility: Ages 60 and Older, Does Not Accept Healthy Volunteers

The purpose of this research study is to assess which antidepressants work the best in older adults who have treatment-resistant depression (TRD).

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

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.

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.

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.

Cognitive Behavior Therapy for Depression

Study Type: Interventional
Start Date: July 31, 2009
Location: New York, New York
Eligibility: Ages 18–65, Does Not Accept Healthy Volunteers

Psychological mindedness(PM) is a metacognitive process in which the person uses his cognitive and affective abilities to understand his thoughts, feelings, and his behaviors as they interact with his internal experiences and his external experiences in the world. It dynamically modifies his behavior to move towards self-actualization in a manner positive to himself and the world. We investigate whether the assessment of PM can distinguish depressed patients who benefit from CBT.

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 17 Months–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.

The Role of Hormones in Postpartum Mood Disorders

Study Type: Interventional
Start Date: April 26, 1996
Location: Bethesda, Maryland
Eligibility: Females, Ages 18–50, Does Not Accept 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 (a separate protocol done in collaboration with NICHD).

Evaluation of the Genetics of Bipolar Disorder

Study Type: Observational
Start Date: August 11, 1994
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.

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.

Study of Premenstrual Syndrome and Premenstrual Dysphoria

Study Type: Observational
Start Date: March 9, 1984
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.