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and treatment of mental illnesses.

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

Featured Studies

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


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

Study Type: Interventional
Start Date: November 27, 2022
Eligibility: 22 Years to 70 Years, Does Not Accept Healthy Volunteers
Location(s): National Institutes of Health Clinical Center, Bethesda, Maryland, United States

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

...


Long-term Observation of Participants With Mood Disorders

Study Type: Observational
Start Date: November 27, 2022
Eligibility: 18 Years and Older, Accepts Healthy Volunteers
Location(s): National Institutes of Health Clinical Center, Bethesda, Maryland, United States

Background:

More than 12,000 people have taken part in research at the Experimental Therapeutics & Pathophysiology Branch at the National Institute of Mental Health Intramural Program. This has led to advances in the treatment of depression, bipolar disorder, and suicide risk. Researchers want to follow up with this group to see if they continue to have mental health symptoms and receive psychiatric treatments.

Objective:

To learn the long-term impact of depression, bipolar disorder, and suicide risk.

Eligibility:

Adults ages 18 and older who signed consent for Protocol 01-M-0254 over a year ago.

Design:

This study has 2 phases: an online phase and a telephone phase. It has no in-person or face-to-face contact.

In Phase 1, participants will fill out online surveys. They will access the surveys through the study website. The questions will focus on their current thoughts and feelings. The surveys will also ask about their current treatments for their mental health symptoms. At the end of the surveys, they will be asked if they would like to take part in Phase 2. If so, they will mark yes. Phase 2 includes a phone interview. They will be contacted by email to schedule the interview.

In Phase 2, participants will be asked more in-depth questions about how they are feeling. They will also be asked which psychiatric medicines and treatments they have used since they left NIH.

In both phases, participants can skip any questions they do not want to answer.

The online surveys will take 30 minutes to complete. The phone interview will last 1-4 hours.

The information that participants give in this study may be linked to their other NIH research records.


Behavioral Activation and Medication Optimization In Older Adults Undergoing Cardiac Surgery

Study Type: Interventional
Start Date: November 5, 2022
Eligibility: 60 Years and Older, Does Not Accept Healthy Volunteers
Location(s): Washington University in St. Louis, Saint Louis, Missouri, United States

This Hybrid 1 Study will test the effectiveness of a bundled intervention comprised of behavioral activation and medication optimization in reducing symptoms of depression and anxiety in older adults undergoing cardiac surgery (compared with usual care), while examining implementation outcomes.


Social Media-Based Parenting Program for Women With Postpartum Depressive Symptoms: Impact on Child Development

Study Type: Interventional
Start Date: October 24, 2022
Eligibility: Females, 18 Years and Older, Does Not Accept Healthy Volunteers
Location(s): Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States

The long-term goal is to develop effective parenting strategies to facilitate optimal child development for mothers suffering with PPD symptoms. The overall objective for this application is to study whether this program combined with online depression treatment leads to more responsive parenting (target) and signals improved child language, socioemotional and cognitive development (outcomes) compared to depression treatment alone. Findings from this application can be used to inform a future study to test the effectiveness and implementation of this social media-based parenting program.


Evaluating tDCS Brain-stimulation in Depression Using MRI

Study Type: Interventional
Start Date: October 20, 2022
Eligibility: 20 Years to 55 Years, Does Not Accept Healthy Volunteers
Location(s): University of California Los Angeles (UCLA), Los Angeles, California, United States

Patients, physicians, and those who fund depression research are keenly interested in depression treatments that do not involve taking medications. One promising candidate treatment is transcranial direct current stimulation (tDCS), a low-cost technique that involves placing electrodes on specific scalp locations and using a 9-volt battery to cause a small amount of electricity to pass through parts of the brain. Depending on the direction of electrical flow, tDCS can make brain cells (neurons) more likely or less likely to generate their own electrical signals. When evaluated as a treatment, tDCS is typically done in daily sessions over a period of two weeks.

One of the challenges of tDCS is to work out the best possible positioning of electrodes and direction of electricity flow to gradually cause lasting changes in brain activity in ways that might be expected to improve depression. To address this challenge, the investigators are using MRI to take pictures of the brain during tDCS. This data will help us better understand the short-term effects of tDCS in depression and help us learn how to customize future treatments to cause a lasting beneficial response.

Patients with depression between the ages of 20-55 years are eligible to take part in this research. Potential participants will undergo:

An assessment to confirm eligibility. This will take place over a secure videoconference call lasting no more than 3 hours.

Two in-person study visits lasting 30 min and 2-1/2 hours respectively. In the first visit, the investigators will use the MRI to take a picture of the brain and head structure to determine appropriate locations for placing the tDCS electrodes at the start of the second visit. Following electrode placement, an MRI scan will be performed to take pictures of the brain during tDCS. Depending on the study arm,

Participants may receive 'active' or 'sham' tDCS. The 'sham' condition is identical to the 'active' tDCS in every way except that it involves minimal tDCS and is designed to help rule out effects unrelated to the administered tDCS electricity. Participants may also be asked to perform a mental task during MRI.

All participants will be compensated $150 + parking upon completion of all study-visits.


CBT Enhanced With Social Cognitive Training vs. CBT Only With Depressed Youth

Study Type: Interventional
Start Date: October 10, 2022
Eligibility: 13 Years to 17 Years, Does Not Accept Healthy Volunteers
Location(s): Judy Garber, Nashville, Tennessee, United States

Depression in youth is a serious public health concern for which more personalized treatments are needed. This randomized controlled trial will test the effect of an intervention aimed at enhancing social cognitive capacities (e.g., ability to take another's perspective), thereby making treatment of depression in youth more efficient and effective. Participants in the R33 (N=82) will be youth between ages 13- through 17-years-old currently experiencing depression. Youth will be randomized to either an enhanced CBT intervention that teaches social cognitive skills, particularly social perspective taking and theory of mind (CBTSCT) as compared to CBT only. The primary target is improvement in both social cognitive skills and depressive symptoms at post-treatment and at a 6-month follow-up.


Transcranial Electric Stimulation Therapy (TEST) for Treatment Resistant Depression (TRD

Study Type: Interventional
Start Date: October 6, 2022
Eligibility: 25 Years to 64 Years, Does Not Accept Healthy Volunteers
Location(s): National Institutes of Health Clinical Center, Bethesda, Maryland, United States

Background:

People with TRD are often helped by electroconvulsive therapy (ECT). But ECT can affect memory and thinking. Researchers want to study a treatment called TEST that uses less electricity.

Objective:

To study the safety and feasibility of TEST and assess its antidepressant effects.

Eligibility:

Adults aged 25-64 with major depression that has not been relieved by current treatments.

Design:

Participants will be admitted to the NIH Clinical Center for 5 18 weeks over 2 3 treatment phases. Their medications may be adjusted.

Participants will be interviewed about their depression, side effects, and other treatments they are receiving. They will complete questionnaires. They will give blood and urine samples. Their brain waves and heart rhythm will be recorded. They will take tests of memory, attention, mental functioning, and thinking.

Participants will have magnetic resonance imaging (MRI) scans of the head and brain. They will lie on a table that slides in and out of the scanner. Pictures of brain chemicals will also be taken. They may complete tasks during the MRI.

Participants will receive TEST and/or sham treatments. They may receive optional ECT. An intravenous catheter will be placed in an arm vein to receive general anesthesia. Two electrodes will be placed on the front of their head. An electric current will be passed from the ECT machine through the electrodes. For sham treatments, they will not receive the electric current. Their breathing, heart rate, brain function, blood pressure, and body movements will be measured.

Participants will have 7 follow-up visits over 6 months. Visits can be done via telehealth.

Participation will last for up to 42 weeks.


Ketamine Versus Midazolam for Recurrence of Suicidality in Adolescents

Study Type: Interventional
Start Date: October 3, 2022
Eligibility: 13 Years to 18 Years, Does Not Accept Healthy Volunteers
Location(s): UT Southwestern Medical Center, Dallas, Texas, United States

This project aims to examine the efficacy of ketamine, a rapidly acting medication shown to decrease suicidality in adults in as short as hours or days, as opposed to weeks.

The study design is a double-blind, randomized, active-control trial of adolescents (ages 13-18 years) with recent suicidal behaviors (suicide attempt or increased suicidal ideation). All participants must be receiving standard of care treatment which may range broadly from both outpatient and inpatient programs which include clinically indicated psychosocial and/or psychopharmacological treatments. Ketamine/midazolam treatment will occur twice weekly during the first two weeks of the study, followed by weekly assessments through week 12.


Neural-Derived Plasma Exosomal MicroRNAs As Promising Novel Biomarkers for Suicidality and Treatment Outcome in Adolescents

Study Type: Interventional
Start Date: October 1, 2022
Eligibility: 10 Years to 24 Years, Accepts Healthy Volunteers
Location(s): University of Alabama at Birmingham, Birmingham, Alabama, United States; UAB Huntsville Regional Medical Campus, Huntsville, Alabama, United States

This study is dedicated to help identify biomarkers for depression and suicide. The purpose of the study is to better understand these links to improve medical and psychiatric care in the future. This research is also to test the effects of standard treatment of depression on improvement in depressive and suicidal behavior and on biomarkers (e.g. miRNA) for these disorders.


Glutamatergic Adaptation to Stress as a Mechanism for Anhedonia and Treatment Response With Ketamine

Study Type: Interventional
Start Date: September 30, 2022
Eligibility: 18 Years to 65 Years, Accepts Healthy Volunteers
Location(s): Emory University, Atlanta, Georgia, United States

The main purpose of this study is to investigate the effects of ketamine on decision-making and emotion processing in a sample of individuals diagnosed with Major Depressive Disorder (MDD).


Brain, Emotions, and Mind-Wandering

Study Type: Interventional
Start Date: September 23, 2022
Eligibility: 11 Years to 13 Years, Does Not Accept Healthy Volunteers
Location(s): Western Psychiatric Hospital, Pittsburgh, Pennsylvania, United States

Mood lability is an important transdiagnostic problem that is associated with poor psychosocial function and suicidal thoughts, and is a predictor of mood disorder onset, especially in youth at familial risk. Thus, particularly in youth with a family history of mood disorder, an intervention to target mood lability during a key period of development could improve outcomes. This study will allow us to test neurobehavioral mechanisms of a mindfulness-based intervention to target mood lability in early adolescents at high risk for developing mood disorders. Through this randomized controlled trial, the investigators will better understand how and for whom mindfulness interventions work, which will lead to more targeted interventions to improve emotion regulation during this key developmental period.


Competitive Revision for CLARO: Collaboration Leading to Addiction Treatment and Recovery From Other Stresses

Study Type: Interventional
Start Date: August 31, 2022
Eligibility: 18 Years and Older, Does Not Accept Healthy Volunteers
Location(s): First Choice Community Healthcare - South Broadway Medical Center, Albuquerque, New Mexico, United States; First Choice Community Healthcare - Los Lunas Medical/Dental Center, Los Lunas, New Mexico, United States; First Choice Community Healthcare - Edgewood Medical/Dental Center, Edgewood, New Mexico, United States; First Choice Community Healthcare - Belen Medical Center, Belen, New Mexico, United States; First Choice Community Healthcare - Alamosa Medical Center, Albuquerque, New Mexico, United States; First Choice Community Healthcare - North Valley Medical Center, Albuquerque, New Mexico, United States; First Choice - Alameda Medical Center, Albuquerque, New Mexico, United States; First Choice Community Healthcare - South Valley Medical/Dental Center, Albuquerque, New Mexico, United States

The purpose of this study is to develop and then test an enhanced version of the parent study's collaborative care intervention for co-occurring disorders (CC-COD) to reduce the risk of suicide and overdose among individuals with opioid use disorder (OUD) in combination with PTSD/depression. The parent study is CLARO, Collaboration Leading to Addiction Treatment and Recovery from Other Stresses (NCT04559893).


Treatment Research Investigating Depression Effects on Neuroimmune Targets (TRIDENT)

Study Type: Interventional
Start Date: August 30, 2022
Eligibility: 18 Years and Older, Does Not Accept Healthy Volunteers
Location(s): University of Miami, Miami, Florida, United States

The purpose of this randomized controlled trial is to understand how a cognitive-behavioral treatment (a form of psychological treatment) for depression changes the gut microbiome (micro-organisms that regulate the health of the gut), immune system, and the brain functioning in people living with HIV.


Remote State Representation in Early Psychosis

Study Type: Interventional
Start Date: July 27, 2022
Eligibility: 18 Years to 45 Years, Does Not Accept Healthy Volunteers
Location(s): University of Minnesota, Minneapolis, Minnesota, United States

The purpose of this study is to examine state representation in individuals aged 15-40 who have been diagnosed with a psychotic illness, as well as young adults who do not have a psychiatric diagnosis. State Representation is our ability to process information about our surroundings. The investigators will complete some observational tests as well as a cognitive training clinical trial.


Caregiver Stress and Sleep Study

Study Type: Interventional
Start Date: July 15, 2022
Eligibility: 60 Years and Older, Accepts Healthy Volunteers
Location(s): UPMC Western Behavioral Health, Pittsburgh, Pennsylvania, United States

This study includes a randomized experimental component where therapists will systematically deliver an experimental behavioral probe or a supportive control condition. The aim is to evaluate effects on meaningful health-relevant measures including morning activation levels, depression symptoms, rumination, and aspects brain connectivity previously linked with depression.


Toward Understanding Drivers of Patient Engagement With Digital Mental Health Interventions - Part I

Study Type: Interventional
Start Date: July 7, 2022
Eligibility: 18 Years to 80 Years, Does Not Accept Healthy Volunteers
Location(s): Brigham and Women's Hospital, Boston, Massachusetts, United States

This pilot study is a precursor to a subsequent clinical trial that will test the impact of a set of automated motivational messages on patient engagement with a digital mental health intervention. The pilot study aims to systematically employ patient feedback to develop the automated motivational messages that will be used in the subsequent clinical trial.


Virtual Group Psychoeducational Discussions With Spanish-Speaking Mothers of Infants in Pediatric Primary Care

Study Type: Interventional
Start Date: June 9, 2022
Eligibility: Females, 16 Years to 99 Years, Accepts Healthy Volunteers
Location(s): Johns Hopkins Bayview Medical Center, Baltimore, Maryland, United States

The goal of the proposed research is to test the feasibility and acceptability of a virtual group session which is intended to be offered universally to Spanish-speaking parents of newborns/infants attending pediatric primary care. The virtual session is intended to (1) enhance patient/family education about postpartum depression (PPD) and (2) Provide an orientation to families regarding relevant clinic and community psychosocial support resources available. The investigators will conduct a single-arm, open pilot of the session, which will be co-delivered by existing clinic staff (including social work and community outreach staff). Session contents include (1) Introduction to clinic staff, contacts, and resources (2) A video-recorded testimonial of a patient with a history of perinatal depression followed by a group discussion about/reflection on the video; (3) Review of prevalence and signs of PPD; (4) Discussion of clinic PPD screening procedures and rationale for screening; (5) Discussion of self-care and mood monitoring; (6) Discussion of relevant local resources, including information about availability of primary care resources for parents (including uninsured parents) and information about resources addressing social needs. The overall aim of the project is to Develop and pilot a virtual group augmentation of standard individual well-child care to improve (1) clinic screening procedures, discussion about and initial management of maternal depressive symptoms with immigrant Latinas and (2) patient symptom recognition, symptom disclosure, and subsequent treatment engagement


Community Health Worker Training to Reduce Depression and Substance Use Stigma in TB/HIV Care in South Africa

Study Type: Interventional
Start Date: June 8, 2022
Eligibility: 18 Years and Older, Accepts Healthy Volunteers
Location(s): South African Medical Research Council, Cape Town, Western Cape, South Africa

Poor engagement in care contributes to HIV- and TB-related morbidity and mortality in South Africa (SA). Community health workers (CHWs) are frontline lay health workers who work to re-engage patients who are lost to follow-up (LTFU) in HIV/TB care. Patients with depression and substance use (SU) have a greater likelihood of being LTFU in HIV/TB care, and there is evidence that CHWs may exhibit stigma towards these patients. When CHWs have negative attitudes towards these patients, on average they spend less time with these patients, are less likely to implement evidence-based practices, and deliver less patient-centered care. Therefore, this purpose of this study is to examine the implementation and preliminary effectiveness of a brief training ("Siyakhana"). The purpose of this training is to provide CHWs with psychoeducation, skills, and support around working with HIV/TB patients with depression/SU. The investigators will assess the training's implementation and changes in CHWs' stigma towards HIV/TB patients with depression/SU.


The Feasibility of Engage Therapy With Video Support for Homebound Older Adults

Study Type: Interventional
Start Date: May 12, 2022
Eligibility: 60 Years and Older, Does Not Accept Healthy Volunteers
Location(s): Weill Cornell Medicine, New York, New York, United States

The primary aim in this pilot project is to test the feasibility, acceptability and impact (decreased depressive symptoms) of a brief behavioral treatment for depression (Engage) combined with video social support (PRISM 2.0) among socially isolated/lonely case management clients who endorse depressive symptoms. Eligible participants will be offered the combination of Engage and Prism 2.0, called Engage-Prism. The investigators hypothesize that the intervention (Engage Therapy With Video Support) will be accepted by participants, improve depressive symptom, and be feasible to complete.


Evaluation of MoodRing on Improving the Quality of Depression Management in Adolescents

Study Type: Interventional
Start Date: May 12, 2022
Eligibility: 12 Years to 18 Years, Does Not Accept Healthy Volunteers
Location(s): Center for Adolescent and Young Adult Health, Pittsburgh, Pennsylvania, United States

The MoodRing intervention is a mobile application for adolescents, parents, and an accompanying web-based clinician portal which enables adolescents to monitor their mood through the use of passively collected smartphone data. This randomized controlled trial will evaluate whether MoodRing as compared to usual care improves the quality of depression management.


Addressing Intimate Partner Violence, Mental Health, and HIV in Antenatal Care

Study Type: Interventional
Start Date: April 26, 2022
Eligibility: Females, 18 Years and Older, Does Not Accept Healthy Volunteers
Location(s): Malvern Clinic, Johannesburg, Gauteng, South Africa

This quasi-experimental feasibility study recruit n=40 participants from each of two public antenatal clinics in Johannesburg, South Africa. Using the Bowen et al. approach, key feasibility study questions will be those around acceptability, implementation, and promising effects on intermediate variable. While this pilot trial is not powered to determine efficacy, it can help establish whether intervention targets the appropriate intermediate mechanisms (i.e. primary endpoints of IPV exposure and depressive symptoms) and moves intended outcomes in the right direction (i.e. towards better adherence as measured by self-reported adherence).


WellPATH-PREVENT: A Mobile Intervention for Middle-Aged and Older Adults Hospitalized for Suicidal Ideation or Attempt

Study Type: Interventional
Start Date: April 22, 2022
Eligibility: 50 Years to 90 Years, Does Not Accept Healthy Volunteers
Location(s): Weill Cornell Institute of Geriatric Psychiatry, Weill Cornell Medicine, White Plains, New York, United States

The goal of this project is to test whether WellPATH-PREVENT (a novel, mobile psychosocial intervention) improves a specific aspect of emotion regulation, i.e., cognitive reappraisal ability, and reduces suicide risk in middle-aged and older adults (50-90 years old) who have been discharged after a suicide-related hospitalization (i.e. for suicidal ideation or suicide attempt).


Sequential Bilateral Accelerated Theta Burst Stimulation in Adolescents With Suicidal Ideation

Study Type: Interventional
Start Date: April 4, 2022
Eligibility: 12 Years to 18 Years, Does Not Accept Healthy Volunteers
Location(s): Mayo Clinic in Rochester, Rochester, Minnesota, United States

The purpose of this study is to gather information regarding the use of a new type of transcranial magnetic stimulation (TMS) called theta burst stimulation (TBS) for suicidal ideation in adolescents with Major Depressive Disorder (MDD). The investigators hope to learn if this TMS treatment improves suicidal ideation over 10 days and clinical outcomes over 1 year of follow-up.


Examining the Effects of Estradiol on Neural and Molecular Response to Reward

Study Type: Interventional
Start Date: April 1, 2022
Eligibility: Females, 44 Years to 55 Years, Does Not Accept Healthy Volunteers
Location(s): University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States

This proposal will examine the effects of estradiol administration on perimenopausal-onset (PO) anhedonia and psychosis symptoms as well as on brain function using simultaneous positron emission tomography and functional magnetic resonance imaging (PET-MR).


Model-based Electrical Brain Stimulation

Study Type: Interventional
Start Date: February 8, 2022
Eligibility: 18 Years and Older, Does Not Accept Healthy Volunteers
Location(s): University of California, San Francisco, San Francisco, California, United States; University of Southern California, Los Angeles, California, United States

Neuropsychiatric disorders are a leading cause of disability worldwide with depressive disorders being one of the most disabling among them. Also, millions of patients do not respond to current medications or psychotherapy, which makes it critical to find an alternative therapy. Applying electrical stimulation at various brain targets has shown promise but there is a critical need to improve efficacy.

Given inter- and intra-subject variabilities in neuropsychiatric disorders, this study aims to enable personalizing the stimulation therapy via i) tracking a patient's own symptoms based on their neural activity, and ii) a model of how their neural activity responds to stimulation therapy. The study will develop the modeling elements needed to realize a model-based personalized closed-loop system for electrical brain stimulation to achieve this aim.

The study will provide proof-of-concept demonstration in epilepsy patients who already have intracranial electroencephalography (iEEG) electrodes implanted for their standard clinical monitoring unrelated to this study, and who consent to being part of the study.


The PATHway Study: Primary Care Based Depression Prevention in Adolescents

Study Type: Interventional
Start Date: December 1, 2021
Eligibility: 13 Years to 18 Years, Accepts Healthy Volunteers
Location(s): Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, United States; UT Southwestern Medical Center, Dallas, Texas, United States; Advocate Aurora Health, Park Ridge, Illinois, United States; Northshore University HealthSystem, Glenview, Illinois, United States; UI Health, Chicago, Illinois, United States

Prevention of depressive disorders has become a key priority for the NIMH, but the investigators have no widely available public health strategy to reduce morbidity and mortality. To address this need, the investigators developed and evaluated the primary care based-technology "behavioral vaccine," Competent Adulthood Transition with Cognitive-Behavioral Humanistic and Interpersonal Therapy (CATCH-IT). The investigators will engage N=4 health systems representative of the United States health care system, and conduct a factorial design study to optimize the intervention in preparation for an implementation study and eventual dissemination.


Behavioral Activation and Medication Optimization for Perioperative Mental Health

Study Type: Interventional
Start Date: November 17, 2021
Eligibility: 60 Years and Older, Does Not Accept Healthy Volunteers
Location(s): Washington University School of Medicine, Saint Louis, Missouri, United States

Inadequate management of preoperative mental health disorders often contributes to poor postoperative outcomes, including increased rates of readmission, delirium, falls, and mortality. However, very little work has been done to improve perioperative mental health. In particular, there have been limited systematic efforts that identify evidence-based behavioral and pharmacological strategies that were originally developed for depression and anxiety in otherwise medically well psychiatric patients. A mental health intervention bundle, composed of behavioral and pharmacological strategies, can mitigate anxiety and depression symptoms during the perioperative period. However, lacking is conclusive evidence on effectiveness of such an intervention bundle focused on the delivery of perioperative mental health care in older surgical patients. Towards this end, the investigators will develop and test an intervention bundle that encompasses: (1) behavioral activation, and (2) medication optimization.


Investigating the Causal Role of Prefrontal Control in Decision-making in Patients With Anhedonia

Study Type: Interventional
Start Date: November 2, 2021
Eligibility: 18 Years to 65 Years, Does Not Accept Healthy Volunteers
Location(s): University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States

Investigating whether delta-beta cross-frequency transcranial alternating current stimulation can increase goal-directed behavior in participants with major depressive disorder and elevated symptoms of anhedonia.


XEN1101 for Major Depressive Disorder

Study Type: Interventional
Start Date: October 19, 2021
Eligibility: 18 Years to 65 Years, Does Not Accept Healthy Volunteers
Location(s): Baylor College of Medicine, Houston, Texas, United States; Icahn School of Medicine at Mount Sinai, New York, New York, United States

This project is designed to examine the neuronal KCNQ2/3 potassium (K+) channel subtype as a novel treatment target for mood disorders through the administration of the KCNQ-selective channel opener XEN1101 (Xenon Pharmaceuticals).


First choIce Antidepressants: General Practitioner's Treatment Approach in the Czech Republic

Study Type: Observational [Patient Registry]
Start Date: October 15, 2021
Eligibility: 18 Years and Older, Does Not Accept Healthy Volunteers
Location(s): Poliklinika Prosek, Praha, Czechia; MUDr. František Rolinek, s.r.o., Brno, Czechia

According to the local guidelines (Recommendation for General Practitioners), the first choice Anti-Depressant (AD) in Major Depressive Disorder (MDD) in primary care should be selective serotonin reuptake inhibitors (SSRI), e.g. citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, in depression with anxiety and insomnia is preferable trazodone and in severer disorders mirtazapine. Despite all these molecules have a very good antidepressant effect, there are differences in side effect scale and tolerability.

The aim of this Study is describing of real treatment practice and MDD management in primary care - aimed to evaluate effectiveness of the treatments in depression and related symptoms: insomnia, anxiety, anhedonia and sexual dysfunction.

The primary objective of the Study is to describe the diagnostic process and treatment patterns in MDD- treatment of choice (pharmacologic with details of first choice antidepressant) in the office of GP's.

The secondary objective is to evaluate efficiency of the treatments in depression and related symptoms: insomnia, anxiety, anhedonia and sexual dysfunction and to monitor the type of side effects and comedication during the 8-weeks treatment.


Using Transcranial Magnetic Stimulation (TMS) to Understand Hallucinations in Schizophrenia

Study Type: Interventional
Start Date: October 13, 2021
Eligibility: 18 Years to 55 Years, Does Not Accept Healthy Volunteers
Location(s): McLean Hospital, Belmont, Massachusetts, United States

This study uses a noninvasive technique called transcranial magnetic stimulation (TMS) to study how hallucinations work in schizophrenia.

TMS is a noninvasive way of stimulating the brain, using a magnetic field to change activity in the brain. The magnetic field is produced by a coil that is held next to the scalp. In this study the investigators will be stimulating the brain to learn more about how TMS might improve these symptoms of schizophrenia.


Invasive Decoding and Stimulation of Altered Reward Computations in Depression

Study Type: Interventional
Start Date: October 6, 2021
Eligibility: 18 Years to 80 Years, Does Not Accept Healthy Volunteers
Location(s): Icahn School of Medicine at Mount Sinai, New York, New York, United States

Novel invasive neurostimulation stimulation strategies through neurosurgical interventions are emerging as a promising therapeutical strategy for major depressive disorder. These have been applied mostly to the anterior cingulate cortex, but other limbic brain regions have shown promise as anatomical targets for new neurostimulation strategies. The researchers seek to study neural activity in limbic brain areas implicated in decision behavior and mood regulation to identify novel targets for treatment through electrical stimulation. To do this, the study team will record local field potentials (LFPs) from the orbitofrontal cortex, hippocampus and amygdala of epilepsy participants undergoing invasive monitoring (intracranial encephalography, iEEG) during choice behavior. Leveraging the high co-morbidity of depression and intractable epilepsy (33-50%), neural responses will be compared to reward across depression status to identify abnormal responses in depression. Finally, the researchers will use these as biomarkers to guide development of neurostimulation strategies for the treatment of depression.


Predictors of Cognitive Outcomes in Geriatric Depression

Study Type: Interventional
Start Date: September 28, 2021
Eligibility: 60 Years and Older, Does Not Accept Healthy Volunteers
Location(s): UConn Health, Farmington, Connecticut, United States

This study will focus on examining effects of stress on long-term mood and cognitive outcomes of late-life depression. It will also example the neural underpinnings of these changes using structural and functional brain imaging. Understanding how effects of stress in older depressed adults, as well as factors that might minimize those effects, lead to particular mood and cognitive outcomes will inform future development of novel prevention strategies.


Accelerating Implementation of Mindful Mood Balance for Moms

Study Type: Interventional
Start Date: September 27, 2021
Eligibility: Females, 18 Years and Older, Accepts Healthy Volunteers
Location(s): Kaiser Permanente Colorado, Denver, Colorado, United States; HealthPartners, Bloomington, Minnesota, United States; Kaiser Permanente Georgia, Atlanta, Georgia, United States; Kaiser Permanente Southern California, San Diego, California, United States

The Mindful Mood Balance for Moms (MMBFM) study examines whether using an internet program called Mindful Mood Balance for Moms to deliver Mindfulness Based Cognitive Therapy (MBCT) over an 8-week time period, is effective for reducing depression symptoms among pregnant women with a history of prior depression, and studies the effects of implementation strategies on the reach of the MMBFM program. This study will enroll 470 women from Kaiser Permanente Colorado, Southern California, Georgia.

The investigators will compare clinical outcomes between those that receive mental health clinician coaching and those that receive peer coaching throughout the 8-week program. Survey data will be collected at 4 time points throughout the study (baseline, 12 weeks, 3rd trimester, and 3 months postpartum). The cost-effectiveness of both the clinical and peer coaching models at each health care system will be evaluated.

For the implementation portion of the study, 30 OB clinics across the 4 health systems will be randomized in equal numbers to provide clinician facing implementation strategies (e.g., recruitment flyers, script pads, electronic medical record prompts) to encourage engagement in the MMBFM program or to usual care where women are only recruited by the study team with no clinician involvement. The primary outcome for testing clinician facing implementation strategies is reach, the percentage of women outreached who initially engage in the MMBFM program.


Testing THRIVE 365 for Black Sexual Minority Men (On The Daily)

Study Type: Interventional
Start Date: September 14, 2021
Eligibility: Males, 16 Years and Older, Accepts Healthy Volunteers
Location(s): Devin English, Newark, New Jersey, United States

The primary goal of this study is to test a minority stress model of psychological health outcomes for Black sexual minority men (BSMM) while using and not using a novel intervention named THRIVE 365. THRIVE 365 combines mHealth and institutional support elements to provide four areas of support for BSMM: 1) Promote HIV and psychological health knowledge and motivation; 2) Foster a sense of community and positive social connections among BSMM; 3) Connect clients to BSMM-affirming healthcare, including HIV treatment and mental healthcare; 4) Provide resources for housing, transportation, and other economic empowerment. To examine the effects of the intervention, we will utilize a 14-day daily diary study to capture daily intervention engagement, HIV and psychological health outcomes, coping, and experiences of racial and sexual minority stressors. We will first examine main associations between intervention engagement and HIV (antiretroviral [ART] use) and psychological health (depressive symptoms, anxiety symptoms, emotion regulation difficulties outcomes) outcomes, then consider how intervention engagement affects coping and attenuates the impacts of racial and sexual minority stressors during the 14 day period.


Biomarker-guided rTMS for Treatment Resistant Depression

Study Type: Interventional
Start Date: September 1, 2021
Eligibility: 22 Years to 65 Years, Does Not Accept Healthy Volunteers
Location(s): Weill Cornell Medicine, New York, New York, United States

Repetitive transcranial magnetic stimulation (rTMS) is a treatment for depression. The investigators are continuing to learn how to optimize outcomes from rTMS treatment. The purpose of this research project is to use brain network connectivity patterns as measured by resting state functional magnetic resonance imaging (fMRI) to confirm a way to optimize the use of rTMS to treat depression. In addition, the study aims to gain a better understanding of how rTMS influences brain networks.


Fitness for Brain Optimization for Late-Life Depression

Study Type: Interventional
Start Date: August 4, 2021
Eligibility: 60 Years and Older, Does Not Accept Healthy Volunteers
Location(s): UPMC Western Psychiatric Hospital, Pittsburgh, Pennsylvania, United States

Cognitive impairment and brain abnormalities are common and persist after depression remission in those with Late Life Depression (LLD), compounding dementia risk in both individuals with acute and remitted LLD (rLLD). In this study, investigators will examine systemic neural and cognitive benefits of aerobic exercise training in older adults with remitted LLD. This will generate preliminary data regarding neural targets of aerobic exercise training that may translate to cognitive benefits in those with rLLD, a population who remains at high risk for dementia despite successful treatment of depression.


Depression Screening in Black Churches

Study Type: Interventional
Start Date: August 1, 2021
Eligibility: 18 Years and Older, Accepts Healthy Volunteers
Location(s): Columbia University Irving Medical Center Center, New York, New York, United States

The overall aim of this study is to employ Community Health Workers (CHWs) to screen for depression in 30 Black churches and compare the effectiveness of Screening, Brief Intervention, and Referral to Treatment (SBIRT) (Intervention arm) to Referral As Usual (Control arm) on treatment engagement for depression. The investigators will assess patient-level outcomes (Mental-Health Related Quality of Life and depressive symptoms) at 3- and 6-months post-screening and conduct a mixed-methods process evaluation to assess multi-level facilitators and barriers of screening uptake.


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

Study Type: Interventional
Start Date: July 20, 2021
Eligibility: 18 Years to 70 Years, Accepts Healthy Volunteers
Location(s): National Institutes of Health Clinical Center, Bethesda, Maryland, United States

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:

the relationship between peripheral markers of inflammation and COX binding 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:

Dynamic 3D PET brain scan on PET/CT. One venous line for radioligand injection. Arterial line for blood sampling. Transmission (CT) scan will be performed to measure and correct for attenuation. Injection of 20 mCi of [11C]MC1 or [11C]PS13. 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. 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. 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:

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

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). C-reactive protein (CRP) will be measured in the pre-PET blood sample to assess overall inflammatory status in periphery. 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). 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). 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. 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
Eligibility: Females, 18 Years and Older, Does Not Accept Healthy Volunteers
Location(s): University of Michigan, Ann Arbor, Michigan, United States

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.


Antidepressant Effects of TS-161 in Treatment-Resistant Depression

Study Type: Interventional
Start Date: June 10, 2021
Eligibility: 18 Years to 65 Years, Does Not Accept Healthy Volunteers
Location(s): National Institutes of Health Clinical Center, Bethesda, Maryland, United States

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....


A Mobile Health Solution for Homework During CBT

Study Type: Interventional
Start Date: June 10, 2021
Eligibility: 7 Years to 17 Years, Does Not Accept Healthy Volunteers
Location(s): University of South Florida, Tampa, Florida, United States

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.


Life Experiences in Adolescents and the Development of Skills

Study Type: Interventional
Start Date: May 19, 2021
Eligibility: 12 Years to 15 Years, Does Not Accept Healthy Volunteers
Location(s): Western Psychiatric Institute and Clinic, Pittsburgh, Pennsylvania, United States

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
Eligibility: 18 Years to 60 Years, Does Not Accept Healthy Volunteers
Location(s): Massachusetts General Hospital, Boston, Massachusetts, United States

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
Eligibility: 15 Years and Older, Does Not Accept Healthy Volunteers
Location(s): Dartmouth-Hitchcock Clinic, Lebanon, New Hampshire, United States

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.


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

Study Type: Interventional
Start Date: March 5, 2021
Eligibility: 18 Years to 65 Years, Does Not Accept Healthy Volunteers
Location(s): Emory University, Atlanta, Georgia, United States; Yale University, New Haven, Connecticut, United States

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.


Electroconvulsive Therapy Amplitude Titration

Study Type: Interventional
Start Date: March 1, 2021
Eligibility: 50 Years to 80 Years, Does Not Accept Healthy Volunteers
Location(s): University of New Mexico, Albuquerque, New Mexico, United States

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.


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

Study Type: Interventional
Start Date: March 1, 2021
Eligibility: 18 Years and Older, Does Not Accept Healthy Volunteers
Location(s): Universidad Cooperativa de Colombia, Medellín, Colombia; Universidad Nacional Autonoma de México, Mexico City, Mexico

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.


MicroRNA Correlates of Childhood Maltreatment and Suicidality

Study Type: Observational
Start Date: February 26, 2021
Eligibility: 18 Years to 60 Years, Accepts Healthy Volunteers
Location(s): UAB Huntsville Regional Medical Campus, Huntsville, Alabama, United States; University of Alabama at Birmingham, Birmingham, Alabama, United States

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.


Neuroinflammation and Modulating Factors in Depression and HIV

Study Type: Interventional
Start Date: February 1, 2021
Eligibility: 18 Years to 65 Years, Does Not Accept Healthy Volunteers
Location(s): Infectious Diseases Institute, Kampala, Uganda

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.


Online System for Identifying and Addressing Teen Depression in Primary Care

Study Type: Observational
Start Date: February 1, 2021
Eligibility: 12 Years to 99 Years, Accepts Healthy Volunteers
Location(s): Total Child Health, Baltimore, Maryland, United States

A novel web-based module (Teen Depression Module or TDM)has been created for assisting primary care providers (PCPs) in screening for and addressing and referring teens with depression. This is a cluster randomized Quality Improvement study to determine if use of the TDM that includes collecting information on strengths and goals as part of well child care will improve detection of depression, referral success, and teen's use of alternative helping strategies with resulting improvement in depression symptoms.


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

Study Type: Interventional
Start Date: January 29, 2021
Eligibility: 50 Years to 65 Years, Does Not Accept Healthy Volunteers
Location(s): Massachusetts General Hospital, Charlestown, Massachusetts, United States

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.


DTA (Dopaminergic Therapy for Anhedonia) Study

Study Type: Interventional
Start Date: January 29, 2021
Eligibility: 25 Years to 55 Years, Does Not Accept Healthy Volunteers
Location(s): Emory University Hospital, Atlanta, Georgia, United States

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.


Lay-Delivered Behavioral Activation in Senior Centers

Study Type: Interventional
Start Date: January 27, 2021
Eligibility: 60 Years and Older, Does Not Accept Healthy Volunteers
Location(s): Goddard Riverside Community Center and NORC, New York, New York, United States; Progress Village Senior Center, Tampa, Florida, United States; Oaks at Riverview Senior Center, Tampa, Florida, United States; JL Young Apartments (Senior Housing), Tampa, Florida, United States; Brandon Senior Center, Brandon, Florida, United States; SAGE Center Brooklyn at Stonewall House, New York, New York, United States; GenPride Senior Center, Seattle, Washington, United States; West Seattle Senior Center, Seattle, Washington, United States

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.


Slow Wave Induction by Propofol to Eliminate Depression (SWIPED)

Study Type: Interventional
Start Date: January 14, 2021
Eligibility: 60 Years and Older, Does Not Accept Healthy Volunteers
Location(s): Washington University School of Medicine/Barnes-Jewish Hospital, Saint Louis, Missouri, United States

Our overall hypothesis is that sleep slow-wave potentiation by propofol is a therapeutic pathway for enhancing slow wave sleep and alleviating treatment-resistant depression (TRD).


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

Study Type: Interventional
Start Date: January 11, 2021
Eligibility: 18 Years to 65 Years, Accepts Healthy Volunteers
Location(s): Duke Early Phase Clinical Research, Durham, North Carolina, United States

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 2-cohort multiple ascending dose (MAD) study will be conducted. Doses will be administered on days 1, 4, 8, and 11. Standard safety parameters will be monitored, and PK will be evaluated at all dose levels. Finally, a 2-cohort group with received a single dose by slow-infusion IV and have PK samples collected from both blood and cerebrospinal fluid (CSF).


IM Ketamine vs Midazolam for Suicidal ER Patients

Study Type: Interventional
Start Date: January 2, 2021
Eligibility: 18 Years to 65 Years, Does Not Accept Healthy Volunteers
Location(s): Comprehensive Psychiatric Emergency Department of Columbia University Medical Center, New York, New York, United States

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.


Recurrence Markers, Cognitive Burden and Neurobiological Homeostasis in Late-Life Depression

Study Type: Observational
Start Date: December 14, 2020
Eligibility: 60 Years and Older, Accepts Healthy Volunteers
Location(s): University of Illinois at Chicago, Chicago, Illinois, United States

Late-life depression (LLD) is associated with disability, increased risk for cognitive decline and dementia, elevated suicide risk, and greater all-cause mortality. These outcomes are related to depression being a recurrent disorder, with repeated episodes over a patient's lifetime. Recurrence rates (defined as including both relapse and recurrence) are high in LLD.

The goals of this study are to identify neurobiological factors that predict recurrence risk, and examine how cognitive performance changes are both influenced by these neurobiological factors and also predict recurrence risk.


Transcranial Direct Current Stimulation (tDCS) Therapy in Major Depression

Study Type: Interventional
Start Date: December 1, 2020
Eligibility: 18 Years to 65 Years, Does Not Accept Healthy Volunteers
Location(s): University of California, Los Angeles (UCLA), Los Angeles, California, United States

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
Eligibility: Females, 16 Years to 45 Years, Does Not Accept Healthy Volunteers
Location(s): My Khanh Commune Health Center, Cần Thơ, Vietnam; Tan Thoi Commune Health Center, Cần Thơ, Vietnam

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
Eligibility: 18 Years to 65 Years, Does Not Accept Healthy Volunteers
Location(s): New York State Psychiatric Institute, New York, New York, United States

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.


In-person vs. Remote Wellness Support

Study Type: Interventional
Start Date: November 24, 2020
Eligibility: 18 Years to 65 Years, Does Not Accept Healthy Volunteers
Location(s): University of Texas Health Science Center - Department of Psychiatry, San Antonio, Texas, United States

The study team will use components of the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework to compare Cognitive Adaptation Training (CAT) to Remotely delivered Cognitive Adaptation Training (R-CAT) 1-9 within a managed care organization (MCO), targeting members with serious mental illness (SMI) needing assistance with the regular taking of medication.


Cognitive Fitness for Depression in Older Adults

Study Type: Interventional
Start Date: November 15, 2020
Eligibility: 60 Years and Older, Does Not Accept Healthy Volunteers
Location(s): UConn Health, Farmington, Connecticut, United States

This research is being done to determine if computerized administered cognitive fitness activities will improve thinking and depression in older depressed adults who are being treated with antidepressants. The investigators are also interested in whether participating in the treatment will result in changes to brain activity measured with magnetic resonance imaging (MRI).


Depression Prevention in Older Spousally-bereaved Adults

Study Type: Interventional
Start Date: October 20, 2020
Eligibility: 60 Years and Older, Does Not Accept Healthy Volunteers
Location(s): UPMC: WPIC- Bellefield Towers, Pittsburgh, Pennsylvania, United States

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
Eligibility: 50 Years to 85 Years, Does Not Accept Healthy Volunteers
Location(s): Weill Cornell Medicine, New York, New York, United States

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.


PEERS Plus mHealth Enhanced Peer Support

Study Type: Interventional
Start Date: October 15, 2020
Eligibility: 50 Years and Older, Does Not Accept Healthy Volunteers
Location(s): Massachusetts General Hospital, Boston, Massachusetts, United States

The goal of this intervention study is to design and learn whether peer support that is delivered through video chats and texting can decrease depression among older adults. Participants will be assigned to a peer support program where they will receive 8 video chats with a peer mentor who provide social support and supportive texts over 8 weeks.


Text 2 Connect- Texting Intervention for Mental Health Treatment Utilization

Study Type: Interventional
Start Date: October 1, 2020
Eligibility: 18 Years and Older, Does Not Accept Healthy Volunteers
Location(s): Children's Community Pediatrics (CCP- Waterdam) of Children's Hospital of Pittsburgh UPMC, McMurray, Pennsylvania, United States; Child and Adolescent Bipolar Spectrum Services (CABS) Center, Pittsburgh, Pennsylvania, United States; STAR Center, Pittsburgh, Pennsylvania, United States

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
Eligibility: 25 Years to 55 Years, Does Not Accept Healthy Volunteers
Location(s): Emory Clinic, Atlanta, Georgia, United States

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
Eligibility: 18 Years and Older, Does Not Accept Healthy Volunteers
Location(s): Trinity Lutheran Church, Hillsdale, Michigan, United States; Jonesville First Presbyterian Church, Jonesville, Michigan, United States

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
Eligibility: 25 Years to 50 Years, Accepts Healthy Volunteers
Location(s): University of Illinois at Chicago, Chicago, Illinois, United States

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
Eligibility: 18 Years to 65 Years, Does Not Accept Healthy Volunteers
Location(s): Laureate Institute for Brain Research, Tulsa, Oklahoma, United States

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. In addition, by including peripheral blood draws and measures of grace matter volume, the project will also accomplish the following aims: (1) Determine whether kynrenine metabolites measures peripherally may be beneficial as a biomarker of treatment response and (2) determine whether there is an association between change in kynurenine metabolites and changes in gray matter volume with treatment.

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.


Designing an Implementation Strategy for Delivering Routine Mental Health Screening and Treatment

Study Type: Interventional
Start Date: August 12, 2020
Eligibility: 16 Years to 30 Years, Does Not Accept Healthy Volunteers
Location(s): University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States

African Americans living with chronic health conditions are more likely to experience depression and other mental health disorders than their healthy counterparts, and are more likely to experience severe depression than whites, but less likely to be diagnosed or receive treatment. One especially vulnerable group is patients with sickle cell disease (SCD), a genetic blood disorder that primarily affects people of African descent, many of whom live in disadvantaged circumstances and are cared for in under-resourced settings. SCD causes severe acute and chronic pain, end-organ damage, and early mortality. Patients transitioning from adolescence to adulthood (ages16-30) are at high risk for mental health disorders and suicide.

Using mobile technology, the investigators can provide high-quality, evidence-based behavioral mental health treatment that reaches patients in different settings. Digital cognitive behavioral therapy (CBT) is effective for treating depression and anxiety and can be brought to scale at low cost. Despite the promise of digital CBT, there are barriers to its widespread use, particularly in low-resource settings serving minorities. Qualitative data show that cultural factors-lack of relatability, representation, and perceived stigma regarding mental health treatment-limit engagement with digital CBT programs. Population-and setting-specific adaptations to interventions can lead to their successful implementation and wider use. The investigators will work with a digital CBT program to decrease stigma and make it more relatable and relevant to young adults with SCD, by devising changes to advertising and promotion, and tailoring communication with an integrated health coach, Aim 1: Use implementation science (ImS) and human-centered design methods to define the barriers to delivering routine mental health screening and digital CBT to adolescents and young adults with SCD. Aim 2: Rapidly iterate, test, and evaluate adaptations to the implementation strategy for a coach-enhanced digital mental health service. Aim 3: Demonstrate that a population-specific implementation strategy improves engagement with a digital CBT-based mental health service.

The investigators will capitalize on our mobile technology tools, interdisciplinary expertise, and community-based partnerships to investigate the implementation of digital CBT into low-resource clinics and community-based organizations serving adolescents and adults with sickle cell disease.


Trial to Test Effectiveness of Depression Intervention for Mistreated Older Adults

Study Type: Interventional
Start Date: July 15, 2020
Eligibility: 55 Years to 100 Years, Does Not Accept Healthy Volunteers
Location(s): Weill Cornell Medicine, New York, New York, United States

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.


Models of Auditory Hallucination

Study Type: Interventional
Start Date: February 27, 2020
Eligibility: 18 Years to 45 Years, Does Not Accept Healthy Volunteers
Location(s): Connecticut Mental Health Center (CMHC), New Haven, Connecticut, United States

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.


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
Eligibility: 18 Years to 70 Years, Does Not Accept Healthy Volunteers
Location(s): National Institutes of Health Clinical Center, Bethesda, Maryland, United States

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.


Multi-modal Assessment of Gamma-aminobutyric Acid (GABA) Function in Psychosis

Study Type: Interventional
Start Date: January 16, 2020
Eligibility: 16 Years to 60 Years, Accepts Healthy Volunteers
Location(s): University of Michigan, Ann Arbor, Michigan, United States

The purpose of this study is to better understand mental illness and will test the hypotheses that while viewing affective stimuli, patient groups will show increased blood oxygenation level dependent (BOLD) signal by fMRI after lorazepam.

This study will enroll participants between the ages of 16 and 60, who have a psychotic illness (such as psychosis which includes conditions like schizophrenia, schizoaffective disorder, and mood disorders). The study will also enroll eligible participants without any psychiatric illness, to compare their brains.

The study will require participants to have 3-4 sessions over a few weeks. The initial assessments (may be over two visits) will include a diagnostic interview and several questionnaires (qols) to assess eligibility. Subsequently, there will will be two separate functional magnetic resonance imaging (fMRI) sessions in which lorazepam or placebo will be given prior to the MRI. During the fMRI the participants will also be asked to answer questions. Additionally, the participants will have their blood drawn, women of child bearing potential will have a urine pregnancy test, vital signs taken, and asked to complete more qols.


Adolescent Attention to Emotion Study

Study Type: Interventional
Start Date: October 16, 2019
Eligibility: Females, 13 Years to 15 Years, Accepts Healthy Volunteers
Location(s): Western Psychiatric Institute and Clinic, Pittsburgh, Pennsylvania, United States

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
Eligibility: 18 Years and Older, Does Not Accept Healthy Volunteers
Location(s): Pine Rest Christian Mental Health Services, Grand Rapids, Michigan, United States

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.


Development of a Novel Transdiagnostic Intervention for Anhedonia - R33 Phase

Study Type: Interventional
Start Date: August 1, 2019
Eligibility: 18 Years to 50 Years, Does Not Accept Healthy Volunteers
Location(s): UNC-Chapel Hill School of Medicine, Chapel Hill, North Carolina, United States

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
Eligibility: 18 Years and Older, Does Not Accept Healthy Volunteers
Location(s): Marondera Provincial Hospital, Marondera, Mashonaland East, Zimbabwe

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.


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
Eligibility: Females, 45 Years to 65 Years, Does Not Accept Healthy Volunteers
Location(s): National Institutes of Health Clinical Center, Bethesda, Maryland, United States

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.


Mechanisms of Rumination Change in Adolescent Depression

Study Type: Interventional
Start Date: May 1, 2019
Eligibility: 14 Years to 17 Years, Does Not Accept Healthy Volunteers
Location(s): University of Utah, Salt Lake City, Utah, United States

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.


Reward Function and Therapy for Late-Life Depression

Study Type: Interventional
Start Date: March 14, 2019
Eligibility: 60 Years and Older, Does Not Accept Healthy Volunteers
Location(s): Weill Cornell Medicine, White Plains, New York, United States

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).


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

Study Type: Interventional
Start Date: September 24, 2018
Eligibility: 12 Years to 18 Years, Does Not Accept Healthy Volunteers
Location(s): Mayo Clinic in Rochester, Rochester, Minnesota, United States

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
Eligibility: 18 Years and Older, Does Not Accept Healthy Volunteers
Location(s): University of Texas Southwestern Medical Center, Dallas, Texas, United States; Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, Ontario, Canada

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
Eligibility: 18 Years to 65 Years, Does Not Accept Healthy Volunteers
Location(s): National Institutes of Health Clinical Center, Bethesda, Maryland, United States

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.


An Adaptive Algorithm-Based Approach to Treatment for Adolescent Depression

Study Type: Interventional
Start Date: February 26, 2018
Eligibility: 12 Years to 18 Years, Does Not Accept Healthy Volunteers
Location(s): Institute for Translational Research in Children's Mental Health, Minneapolis, Minnesota, United States

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.


Characterization and Treatment of Adolescent Depression

Study Type: Observational
Start Date: December 28, 2017
Eligibility: 11 Years to 25 Years, Accepts Healthy Volunteers
Location(s): National Institutes of Health Clinical Center, Bethesda, Maryland, United States

This research study seeks to find causes and treatments of depression in teenagers. The study goals are to increase our knowledge of treatments for depression and understand how the brain changes when teenagers have depression. The study will also compare teenagers with depression to those without mental health diagnoses.

This outpatient study is recruiting participants ages 11-17 who are depressed. They must have a pediatrician or other medical provider, be medically healthy, and able to perform research tasks. They may not currently be hospitalized, psychotic or actively suicidal. Teenagers with depression are eligible even if they are taking medication.

The study begins with an evaluation that includes clinical assessment, interviews, and questionnaires.

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

All clinical evaluations, research tasks and visits are free of cost. Participants are compensated for research activities. Parents and teenager must agree to the teenager s participation in research.

The study is conducted at the NIH in Bethesda, Maryland and enrolls participants from the Washington DC Metro region within 50 miles of NIH. Transportation expenses are reimbursed by NIMH.


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

Study Type: Interventional
Start Date: October 1, 2017
Eligibility: 18 Years to 60 Years, Does Not Accept Healthy Volunteers
Location(s): University of Minnesota, Minneapolis, Minnesota, United States

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
Eligibility: Females, 18 Years and Older, Does Not Accept Healthy Volunteers
Location(s): University of Denver, Denver, Colorado, United States

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


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

Study Type: Interventional
Start Date: May 25, 2017
Eligibility: 18 Years to 65 Years, Accepts Healthy Volunteers
Location(s): National Institutes of Health Clinical Center, Bethesda, Maryland, United States

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
Eligibility: 60 Years and Older, Does Not Accept Healthy Volunteers
Location(s): University of Pittsburgh, Pittsburgh, Pennsylvania, United States

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
Eligibility: 21 Years to 65 Years, Does Not Accept Healthy Volunteers
Location(s): Emory University, Atlanta, Georgia, United States

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

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


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

Study Type: Interventional
Start Date: April 1, 2017
Eligibility: Females, 18 Years to 50 Years, Does Not Accept Healthy Volunteers
Location(s): Awf, Swac, Dhaka, Bangladesh

Background (brief):

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

Objectives:

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

Methods:

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

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

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

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

Outcome measures/variables:

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

Acceptability, Adaptability, Demands, Practicality, Implementation, Integration

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


Neurobiology of Suicide

Study Type: Interventional
Start Date: December 1, 2015
Eligibility: 18 Years to 70 Years, Accepts Healthy Volunteers
Location(s): National Institutes of Health Clinical Center, Bethesda, Maryland, United States

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.


Ketamine Alcohol (in Treatment-Resistant Depression)

Study Type: Interventional
Start Date: April 23, 2014
Eligibility: 21 Years to 65 Years, Does Not Accept Healthy Volunteers
Location(s): University of Iowa Health Care, Iowa City, Iowa, United States

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


Cellular Aging and Neurobiology of Depression Study

Study Type: Interventional
Start Date: December 31, 2010
Eligibility: 21 Years to 60 Years, Accepts Healthy Volunteers
Location(s): University of California San Francisco, San Francisco, California, United States

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

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


Cognitive Behavior Therapy for Depression

Study Type: Interventional
Start Date: July 31, 2009
Eligibility: 18 Years to 65 Years, Does Not Accept Healthy Volunteers
Location(s): New York State Psychiatric Institute, New York, New York, United States

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
Eligibility: 18 Years to 65 Years, Accepts Healthy Volunteers
Location(s): National Institutes of Health Clinical Center, Bethesda, Maryland, United States

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:

"<TAB>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.

"<TAB>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
Eligibility: 7 Years and Older, Accepts Healthy Volunteers
Location(s): National Institutes of Health Clinical Center, Bethesda, Maryland, United States

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
Eligibility: 2 Months to 30 Years, Accepts Healthy Volunteers
Location(s): National Institutes of Health Clinical Center, Bethesda, Maryland, United States

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
Eligibility: 7 Years to 60 Years, Does Not Accept Healthy Volunteers
Location(s): National Institutes of Health Clinical Center, Bethesda, Maryland, United States

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
Eligibility: 8 Years to 65 Years, Accepts Healthy Volunteers
Location(s): National Institutes of Health Clinical Center, Bethesda, Maryland, United States

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
Eligibility: 3 Years to 99 Years, Accepts Healthy Volunteers
Location(s): National Institutes of Health Clinical Center, Bethesda, Maryland, United States

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
Eligibility: Females, 18 Years to 50 Years, Accepts Healthy Volunteers
Location(s): National Institutes of Health Clinical Center, Bethesda, Maryland, United States

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
Eligibility: 18 Years and Older, Accepts Healthy Volunteers
Location(s): National Institutes of Health Clinical Center, Bethesda, Maryland, United States

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: January 25, 1993
Eligibility: Females, 40 Years to 65 Years, Accepts Healthy Volunteers
Location(s): National Institutes of Health Clinical Center, Bethesda, Maryland, United States

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
Eligibility: Females, 18 Years to 50 Years, Accepts Healthy Volunteers
Location(s): National Institutes of Health Clinical Center, Bethesda, Maryland, United States

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.