Clinical trials

Background: Pediatric disruptive behavior disorders (DBDs) are characterized by severe irritability, anger, and temper outbursts. The primary way to treat children with DBDs is parent management training (PMT). PMT teaches parents how to reward desired behaviors and not to reward undesired ones. Researchers want to find out if a smartphone app can help parents apply these skills more effectively. Objective: To test a smartphone app to enhance PMT. Eligibility: Children aged 8 to 13 years with DBDs. A parent or guardian is also needed. Design: Parents will have 12 weekly sessions of PMT. PMT teaches them how to manage their child s mood and behaviors. Parents will learn to actively ignore, praise, set limits, and handle temper outbursts. PMT can be either in person or via video. Sessions last 30 to 60 minutes. They will be video and audio recorded. Parents will be divided into 2 groups. Only 1 group will download a smartphone app. The app helps parents practice PMT skills. It offers videos, a resource library, and alerts when a child may be at risk for various behaviors. All parents will be prompted every day to answer questions about their child s mood and their own behavior. These will continue until 12 weeks after their last PMT session. Children will also answer questions on their phone daily for 1 week at a time. They will do this on 3 different weeks, each about 2 months apart. They will also have check-ins by phone every 2 weeks for up to 6 months. Parents will have follow-up calls 3, 6, and 12 months after they finish PMT.

Background: Irritability is defined as proneness to anger that may impair a person's ability to function. It is a common reason for why some children need mental health care. Yet no therapies have been developed just to target irritability. Researchers want to compare different types of therapy for irritability. Objective: To test different types of therapy for children and teens with severe irritability. Eligibility: People aged 8 to 16.5 years with severe irritability. Their parents are also needed. Design: Participants will have 28 study visits in 18 months. They will have a baseline visit. They will answer questions about their mood, behavior, and daily life. All parents and children will have 12 therapy sessions. Sessions will be once a week; they will last 30 to 60 minutes. Some of the child sessions may be done by telehealth. Each parent and child will have 1 of 3 therapy types: Exposure therapy (child). Participants will face things that make them angry. A therapist will help them practice managing their anger. Management therapy (parent). Therapists will coach parents on ways to manage their child s behaviors. Psychoeducation/supportive psychotherapy (child and/or parent). Participants will talk with therapists about their or their child s feelings and behaviors. They will list their problems and goals; build coping skills; learn to relax; improve communication; and work on managing stress. Sessions may be videotaped. Participants may opt out of being recorded. Participants will have phone calls every 2 weeks during therapy. They will answer questions about how they are doing. Follow-up calls will continue for 1 year after therapy.

Background: Attention deficit hyperactivity disorder (ADHD) is common in children. It can cause problems with attention and the ability to control actions and impulses. Obsessive compulsive disorder (OCD) is less common in children but not rare. It involves ongoing thoughts, urges, impulses, and repeated behaviors. Researchers want to study differences in brain activity between healthy children, those with ADHD, and those with OCD. Objective: To learn more about how the brain controls thinking and behavior. Eligibility: People aged 10 to 17 years with ADHD, OCD, or neither. Design: Participants will have 3 to 10 clinic visits in up to 1 year. Each visit will last 2 to 3 hours. Three visits are required: Behavioral. Participants will complete a computer task. Their mood, memory, attention, and thinking skills will be tested. EEG. Participants will undergo electroencephalography (EEG) to measure signals in their brain. Small electrodes will be placed on the scalp. A cap will be stretched over the head. Signals will be recorded while participants rest or do tasks on a computer. MRI. Participants will have a magnetic resonance imaging scan (MRI). They will lie on a table that rolls into a tube. The MRI will take pictures of their brain while they do tasks on a computer. Seven more visits are optional. These include 2 more EEG visits and 2 more MRI visits. Three will be magnetoencephalography (MEG) visits: MEG measures small magnetic field changes in the brain. A helmet with sensors will be placed on the head. Brain changes will be recorded while participants rest or do tasks on a computer.

Background: About 5 million adults in the United States have age-related brain disorders. These include Alzheimer disease (AD), mild cognitive impairment (MCI), and other dementias. The number of people with these disorders will likely increase as the population ages and life span increases. Inflammation is thought to play a role in AD and MCI. Researchers want to know if an enzyme called PDE4B increases inflammation in people with AD or MCI. Objective: To test whether medical imaging using a new radiotracer (\[18F\]PF-06445974) can measure PDE4B in the brains of people with AD or MCI. Eligibility: People aged 50 years and older with AD or MCI. Healthy volunteers are also needed. Design: Participants will have up to 5 clinic visits with 3 imaging scans of the brain. They will have be screened. They will have a physical exam with blood tests. This will include tests of their heart and nerve function, including memory. Participants will have 2 positron emission tomography (PET) scans. One will use a standard radiotracer. The other will use the study radiotracer. They will receive each tracer through a tube attached to a needle inserted into a vein. During the scan with the study tracer, participants will have a second tube inserted into a vein in the wrist; this tube will be used to draw blood during the scan. Participants will lie on a bed that slides into a doughnut-shaped machine. These visits will take about 6 hours each. Participants will have 1 magnetic resonance imaging (MRI) scan. They will lie on a bed that slides into a cylinder. This visit will take up to 2 hours....

The purpose of this study is to use brain imaging technology to measure changes in blood flow to areas in the brain as individuals perform intellectual tasks. This study will use functional magnetic resonance imaging (fMRI) to examine blood flow to areas of the brain as participants engage in tasks associated with visual perception, visual recognition, and memory....

Background: \- Previous studies have shown that people with certain types of brain damage may have particular problems paying attention and processing things that they see. Researchers are interested in comparing how people with brain damage and without brain damage process visual images. Objectives: \- To better understand the areas of the brain involved in paying attention to things that are seen. Eligibility: \- Individuals at least 18 years of age who either have had damage to one or both sides of specific parts of the brain (e.g., stroke, injury, certain neurosurgery procedures) or are healthy volunteers. Design: * The study involves 4 to 10 visits to the NIH Clinical Center over 1 to 2 years. Each visit will last approximately 2 hours. * Participants will be screened with a medical history and physical examination, and may have the cognitive testing described below during the same visit. * On the first visit and for at least one visit thereafter, participants will have cognitive testing to evaluate thinking and memory. These tests will be either written tests or computer-based tests. * Some participants will qualify for functional magnetic resonance imaging (fMRI) as part of the study. This part will involve a decision-making task that will be performed on a computer during the fMRI scan. Additional scans may be required as directed by the study doctors. * Some randomly selected participants will be asked to have magnetoencephalography (MEG), a procedure to record very small magnetic field changes produced by brain activity. * During the behavioral training, or fMRI or MEG scanning, participants may be monitored with equipment to track eye movements.

Background: Researchers have developed a new radioactive tracer (11C-ARMI). A tracer is a drug that attaches itself to other chemicals in the body and lights up so that the chemicals can be seen in imaging scans. The new tracer may be able to help them with many diseases, such as Alzheimer s disease and Parkinson s disease. Researchers want to test the new tracer in healthy people. Objective: To test a new tracer (11C-ARMI) during imaging scans of the brain and body in healthy people. Eligibility: Healthy people aged 18 years and older. They must have been screened under protocols 01-M-0254 or 17M0181. Design: All participants will have a positron emission tomography (PET)/computed tomography (CT) scan. Before the scan, they will have blood and urine tests and a test of their heart function. The tracer will be given through a tube attached to a needle inserted into a vein in the arm. They will lie on a padded bed that fits inside a doughnut-shaped machine; the machine uses x-rays to create images of the inside of the body. Some participants will have a PET/CT scan of their whole body. They will need only 1 visit. Some participants will have a PET/CT scan of only their brain. They will have up to 2 visits. On the second visit, they will have a magnetic resonance imaging (MRI) scan of the brain. For the MRI, they will lie on a table that slides into a cylinder. The MRI uses magnetic fields to create images of the inside of the body. Participants will receive a follow-up call to check on their well-being after their PET/CT scans.

Background: Impulsivity is acting 'without thinking.' Compulsivity is being overly inflexible. People vary in how impulsive or compulsive they are. Extreme versions of these behaviors play a role in mental disorders. Researchers want to study changes in the brain to learn more about these behaviors. Differences in genes may also play a role. Objective: To learn about genetic \& brain features that explain why levels of impulsivity and compulsivity vary across people. Eligibility: People ages 6 - 80 Design: Participants will be screened with a medical history and medical record review. Participants will talk about their mental and behavioral development. They may discuss topics like drug use and sexual activity. They will complete surveys about their compulsivity and impulsivity. Parents of child participants may also complete these surveys. Participants may take memory, attention, and thinking tests. They may give blood or saliva samples for gene studies and they may give blood to make induced pluripotent stem cells. Participants may have their face and irises photographs taken. Participants may have a magnetic resonance imaging scan. It will take pictures of their brain. The scanner is shaped like a cylinder. Participants will lie on a table that slides in and out of the scanner. A coil will be placed over their head. They will lie still, watch a movie, and play a game. Participants may ask family members to join the study. Researchers are particularly interested in recruiting twin pairs to the study. Participants under age 25 may repeat these tests every 1-2 years until they turn 25 or until the study ends. For those over age 25, participation will last less than 1 month.

Background: SARS-CoV-2 is the virus that causes COVID-19. Some people who recover from COVID-19 have long-term symptoms that affect the brain. These include headaches; loss of taste and smell; sleep problems; thinking problems; depression; and anxiety. Researchers want to know if a tracer (a substance that is injected into a person s body before an imaging scan) can help identify inflammation in people with these brain disorders. Objective: To see if a radioactive tracer (\[11C\]PS13) can highlight brain inflammation in those who had COVID-19 but still have symptoms that affect the brain. Eligibility: Adults aged 18 to 70 years with post COVID-19 brain disorders who are enrolled in protocol 000089 or 000711. Healthy volunteers are also needed. Design: Participants will have up to 5 clinic visits. Participants will be screened. They will have blood tests and a test of their heart function. They will have imaging scans: Magnetic resonance imaging (MRI): They will lie on a table that slides into a metal tube. Pictures will be taken of the brain. Positron emission tomography (PET): A needle attached to a thin tube will be inserted into a vein in the arm. The tracer will be injected through the tube. Another needle attached to a thin tube will be inserted into the wrist or inside of the elbow of the other arm to draw blood. They will lie still on a bed while a machine captures images of their brain. The scan will last about 2 hours. Study involvement is 11 to 14 weeks....

Background: PDE4D is a protein in the body that plays a role in thinking and depression. This protein may play a major role in disorders such as Alzheimer disease or major depressive disorder. To learn more about these disorders, researchers want to be able to detect levels of PDE4D in the brain. 11C-JMJ-129 is a new radiotracer (a radioactive substance that highlights parts of the body during imaging scans) that was developed to attach only to PDE4D. However, early human studies showed that the tracer may break down in the body and create byproducts that interfere with the brain signal, making the results harder to interpret. This study will test whether a medication called disulfiram can improve PET imaging with 11C-JMJ-129. Disulfiram blocks an enzyme in the body that may be responsible for breaking down the tracer. By reducing this breakdown, the study aims to improve the quality and accuracy of brain images. The results may help researchers better measure PDE4D in the brain and support future studies of brain disorders. Objective: To test the new radiotracer 11C-JMJ-129, with and/or without disulfiram pretreatment during imaging scans in healthy volunteers. Eligibility: Healthy people aged 18 years and older who had a screening assessment under protocol 01-M-0254. Design: Participants will have 1 to 4 clinic visits. Participants will be screened. They will have a physical exam. They will have blood tests and a test of their heart function. Participants will undergo 1 or more of these scans: A positron emission tomography (PET) scan of the whole body. The radiotracer will be injected through a tube placed in a vein in the arm. Participants will lie on a table while a donut-shaped machine passes over them. Blood will be drawn from the arm during this scan. In Phase 5, disulfiram (500 mg orally) will be administered approximately 20 hours before the post-disulfiram PET scan A magnetic resonance imaging (MRI) scan of the brain. Participants will lie on a table that slides into a tube. A PET scan of the brain. These participants will be injected with the radiotracer. They will lie on a table with their head in the scanner. Participants will be called within 3 days after each PET scan for a check on their health.

Background: People with alcohol use disorder (AUD) also often have bouts of depression called major depressive episodes (MDEs). People having MDEs have been found to have low levels of a protein called PDE4B in the brain. Researchers want to find out if people with AUD also have low levels of PDE4B. This research may help lead to better treatments for AUD. Objective: To find out (1) if PDE4B levels are lower in people who are withdrawing from AUD and (2) if their PDE4B levels go up after they abstain from alcohol for 3 to 4 weeks. Eligibility: Adults aged 18 to 70 years with AUD. They must be enrolled in protocol 14-AA-0181. Design: Participants enrolled in protocol 14-AA-0181 will stay in the clinic for 3 to 4 weeks for alcohol withdrawal. During this stay, they will have some added procedures for the current study. Within the first week, participants will have a positron emission tomography (PET) scan of the brain. A needle will be used to guide a thin plastic tube (catheter) into a vein in one arm. An experimental substance called a radioactive tracer will be injected through the catheter. This tracer binds to PDE4B and makes it easier to see the protein in the brain. For the scan, participants will lie on a table that slides into a doughnut-shaped machine. Participants will have a second PET scan toward the end of their stay in the clinic. Participants may also have a magnetic resonance imaging (MRI) scan of the brain. They will lie on a bed that slides into a tube....

Background: Irritability can be defined as an unusually strong response to frustration; these responses may include severe temper outbursts and a constant grumpy mood. Irritability is a common symptom of many mental health disorders. Little is known about how the brain responds to frustration, and few treatments are available for this problem. Researchers want to know more about how the brain responds to frustration. Objective: To learn how the brain responds to frustration. Eligibility: Healthy adults aged 18 to 55 years. They must have been screened through studies 01-M-0254 or 17-M-0181. Design: Participants will have up to 3 study visits in 2 months. Each visit will last up to 4 hours. Visit 1: Participants will be screened. They will have a physical exam. They will complete questionnaires about how often and how easily they get angry or grumpy. They will be trained to use a device that measures hand grip. Visit 2: Participants will have a magnetic resonance imaging (MRI) scan. They will lie on a table that slides into a tube. Padding will hold their head still. Visit 3: Participants will undergo magnetoencephalography (MEG). A cone with detectors will be lowered over their head while they are seated. The MEG will measure the magnetic fields in the participant s brain both while they are resting and while they are doing the frustration task. For the task, they will hold a grip device in each hand. They will use the devices to pick 1 of 2 doors on a computer screen. The task has 3 parts. The participant s face will be filmed during this task.

Background: Brain activity produces magnetic fields. These fields can be measured outside the head. Existing technology, called MEG, measures these fields. Researchers are testing a new type of magnetic field sensor called OPM. They hope it can help pinpoint with very high accuracy where brain activity is generated. Objective: To develop and test a new type of sensor for measuring the magnetic fields produced by brain activity. Eligibility: Healthy people ages 18-65 who had a magnetic resonance imaging (MRI) scan under protocol 17-M-0181. Design: Participants may be asked to complete sessions on both the traditional MEG instrument and the OPM array. For the MEG, 3 small coils will be placed on the participant s face with tape. Their head will be positioned inside the MEG device. For the OPM, sensors are housed in a 3d printed array. The sensors will be attached to a cap placed on the participant s head. For both scans, participants will be seated in a chair inside a magnetically shielded room. They may complete several tasks. In one task, plastic cells will be placed on their fingers. Puffs of air will be sent to these cells, which will stimulate the sense of touch. Other tasks may include the following stimuli: visual (such as checkerboards), auditory (such as beeps and tones), or language (words and letters). Researchers may also obtain recordings while they stimulate the nerve in the participant s forearm using electrical current in small electrodes. Participation is expected to last for 1 day. Additional optional scans may be offered for up to 1 year....

Background: Researchers developed \[11C\]MC1, a radioligand for cyclooxygenase-2 (COX-2). COX-2 is an enzyme induced in the brain during inflammation. Researchers want to see the levels of COX-1 (measured as distribution volume VT) are elevated in the brain of two groups of mood disorders patients undergoing MDE relative to the control group. Objective: To determine whether COX-1 and COX-2 are detectable in the brains of individuals with MDD experiencing a major depressive episode (MDE). Eligibility: People aged 18-70 years with MDD and Healthy Volunteers aged 18 70 years. Design: Group A: MDD participants will be studied with the same dose of \[11C\]MC1 before and after administration of 600 mg celecoxib; the study is neither randomized nor placebo-controlled. Group B: MDD participants, both medicated and unmedicated, will be studied with \[11C\]PS13 and compared to healthy volunteers.. https://nimhcontent.nimh.nih.gov/start/surveys/?s=TJW4RA4WN3LDD988

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....

Background: \- Magnetic resonance imaging (MRI) is a widely used scanning technique to obtain images of the human body and evaluate activity in the brain. A particular MRI method called magnetic resonance spectroscopy (MRS) can be used to study brain chemistry as well, which may help researchers who are studying new treatments for psychiatric illnesses. Researchers are interested in improving current MRI and MRS techniques, as well as developing new MRI and MRS techniques to view and measure brain chemicals and brain activity. Objectives: \- To implement, develop, and optimize brain chemistry imaging techniques using magnetic resonance imaging and magnetic resonance spectroscopy. Eligibility: \- Healthy individuals between 18 and 65 years of age. Design: * This study will involve a screening visit and a scanning visit at the National Institutes of Health Clinical Center. * Participants will be screened with a full medical and physical examination, blood and urine tests, and neurological testing. * During the second visit, participants will have an MRI scan of the brain. (Participants who have received an MRI within the past year will not need to have a second one; the images of the previous scan will be used for this study.) All participants will then have an MRS scan using the same scanning equipment....

The purpose of this protocol is to allow for the careful evaluation of healthy volunteers and individuals with risk for psychiatric disorders or neurodevelopmental disorders, such as autism spectrum disorder for specific protocols at NIH....

Background: PDE4B is a protein in cells that helps turn off certain chemical signals after they ve done their job. It controls inflammation, immune responses, and some brain signaling. Measuring PDE4B levels in the body can help doctors manage a disease or know if a treatment is working. Researchers want to find out if a new tracer (a radioactive substance injected during imaging scans) can help them measure PDE4B in people more effectively. Objective: To test a new tracer (\[11C\]ZTP-1) during imaging scans of the brain and body in healthy people. Eligibility: Healthy people aged 18 and older. They must have been screened under protocols 01M-0254 or 17M0181. Design: Participants will have either 1 or 2 clinic visits. During their first visit, all participants will have a positron emission tomography (PET)/computed tomography (CT) scan. Prior to the scan, they will have blood and urine tests and a test of their heart function. The study tracer will be given through a tube attached to a needle inserted into a vein in the arm. They will lie on a padded bed that fits inside a doughnut-shaped machine; the machine uses x-rays to create images of the inside of the body. Some participants will have a PET/CT scan of their whole body. They will need only 1 visit. The visit will last up to about 8 hours. Some participants will have a PET/CT scan of only their brain. They will also have a magnetic resonance imaging (MRI) scan of the brain. They may need to return for a second visit for the MRI scan. Participants will receive a follow-up call to check on their well-being after their PET/CT scans.

Background: Phosphodiesterase-4B (PDE4B) is a protein in the brain that may play a role in several mental health disorders. Researchers want to know if drinking alcohol increases the binding of a radioactive tracer to PDE4B in the brain because of increased activity and/or amount of the protein. This knowledge may help create new ways to treat people with alcohol use disorder (AUD). Objective: To learn if alcohol increases PDE4B activity in the brain. Eligibility: Healthy people aged 21 to 70 years who drink socially but do not have AUD. They must be enrolled in protocol 14-AA-0181"NIAAA Natural History Protocol". Design: Participants will have up to 4 clinic visits with up to 3 imaging scans of the brain; these will include 1 or 2 positron emission tomography (PET) scans and 1 magnetic resonance imaging (MRI) scan. The first PET scan will be a baseline. Participants will receive a radioactive tracer through a tube inserted into a vein. A second tube will be inserted so that blood can be drawn during the scan. Participants will lie on a bed that slides into a doughnut-shaped machine. This visit will take about 6 hours. For the next PET scan, participants will receive alcohol (ethanol) through a tube in a vein until they have a blood alcohol concentration that is equal to the legal driving limit. This is the same as 4 or 5 drinks for most people. After the scan, participants must remain at the clinic for a few hours until their blood alcohol drops. This visit will take 14 to 16 hours. The MRI scan of the brain will take up to 2 hours in a separate clinic visit.

Background: Major depressive disorder (MDD) is a psychiatric condition. People with MDD have occasional bouts of depressive symptoms; these bouts are called major depressive episodes (MDEs). Researchers want to know if people having MDEs have lower levels of an enzyme called PDE4B in their brains. Primary Objective: To determine whether PDE4B is reduced in the brains of individuals with MDD experiencing a major depressive episode (MDE). Secondary Objectives: To determine the optimal length of scanning and the retest variability and reliability of \[18F\]PF-06445974, and whether PDE4B binding correlates with clinical rating scales. To measure if PDE4B radioligand binding can be blocked by taking apremilast. Eligibility: People aged 18-70 years with MDD. Healthy volunteers are also needed. Design: Participants will have up to 5 clinic visits. Participants will be screened. They will have a physical exam with blood tests. They will have a test of their heart function. Some participants may have a psychiatric assessment; they will answer questions about their state of mind and related topics. Participants will have magnetic resonance imaging (MRI) of the brain. They will lie on a table that slides into a metal cylinder. Participants will have a positron emission tomography (PET) scan. A needle will be used to guide a thin plastic tube (catheter) into a vein in one arm. An experimental substance called a radioactive tracer (\[18F\]PF-06445974) will be injected through the catheter. Participants will lie on a table that slides into a doughnut-shaped machine. The scan will last up to 4 hours with a 15-minute break. Participants blood pressure, heart rate, and breathing will be monitored before, during, and after the PET scan. A second catheter will be inserted in the artery of the wrist so blood can be drawn during the scan. Some participants may return for a second PET scan; have a lung scan or receive apremilast. https://nimhcontent.nimh.nih.gov/start/surveys/?s=KE88DXXPLDFHHTF8

Background: About 5 million adults in the U.S. have Alzheimer s disease or another adult-onset neurodegenerative disorder. Many studies have found that inflammation in the brain contributes to these diseases. Researchers want to find a better way to measure this inflammation. Objective: To learn whether COX-1 and/or COX-2 is elevated in the brains of individuals with neurodegenerative brain disease compared to healthy volunteers. Eligibility: Adults age 18 years and older in good general health who have an adult-onset neurodegenerative dementia, such as AD, FTD, corticobasal syndrome, Huntington s disease, or MCI, ALS and healthy adult volunteers enrolled in protocols 01-M-0254 or 17-M-0181. Design: Participants will be screened with medical history, physical exam with vital signs, and lab tests. They will have a neuropsychological testing. Their heart function will be measured. Participants will have a magnetic resonance imaging (MRI) scan. The MRI scanner is a metal tube surrounded by a strong magnetic field. Participants will lie on a table that slides in and out of the tube. The machine makes noise. Participants will get earplugs. Participants will have 2 PET scans. They will be injected with the study drugs through an intravenous catheter placed in an arm vein. The PET scanner is shaped like a doughnut. Participants will lie on a bed that slides in and out of the scanner. A plastic mask will be molded to their head to keep them from moving. A thin plastic tube will be put into an artery at the wrist or elbow crease area. This will be used to draw blood during the scan. Participants will have 2-5 study visits. Participation lasts 1 week to 4 months, depending on scheduling.

Objective: To screen and create a list of adult volunteers in good health for participation in research studies conducted at the National Institutes of Health (NIH) in Bethesda, Maryland. Develop a normative set of structural and functional brain MRI scans that are linked to healthy research volunteer characteristics. Maximize scientific impact of data from volunteers by broadly sharing with other researchers. Study Population: Adult males and females in general good health who are 18 years of age and older. Design: Adult individuals who are interested in participating in NIMH IRP clinical studies as a healthy research volunteer can directly visit or be directed to visit the study website where they will first consent electronically and then complete a set of online self-report measures. Items may include: demographic information, mental health symptoms, disability status, substance use patterns, handedness and clinical/family history. Individuals who are flagged based on predetermined responses to survey items will be further screened by a member of the study clinical team. If found to be ineligible for the study because of a clinically significant or unstable medical or mental health condition, these individuals will be referred back to the community and/or given information about NIMH clinical studies for which they may be eligible. Respondents with no flags or who pass through additional screening will be scheduled for an in-person assessment. During the outpatient appointment and after in-person informed consent, participants will receive a brief clinical interview to screen for current medical and mental conditions, and risk for self-harm. They will complete assessments of psychological, emotional, physiologic, biological and cognitive functioning. Participants will undergo a physical exam and be asked to provide blood and urine samples for routine clinical labs. Participants can separately consent for an optional baseline brain magnetic resonance imaging (MRI) scan and an optional magnetoencephalography (MEG) exam. All consent forms will explicitly inform participants that if enrolled in the study, their de-identified data will be broadly and publicly shared through NIH-approved data repositories. Participants in this recruitment and characterization study will then be placed on a list of healthy research volunteers from which other NIMH IRP studies may recruit according to the inclusion and exclusion criteria in their respective IRB-approved protocols. Outcome Measures: Outcome measures may include demographic data, mental and medical history and symptoms, results of psychological, emotional, physiologic, biological, and cognitive testing, physical exam and MRI findings....

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

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. ...

Background: \- Many psychiatric, behavioral, and developmental disorders are genetic. This means that they tend to run in families. Some begin in childhood, while others do not appear until adulthood. Researchers want to look at people of all ages who have these disorders that started in childhood. They will also look at relatives of people with these disorders. This information will allow doctors to learn more about childhood behavioral problems and how they are inherited. It may also help doctors treat those disorders. Objectives: \- To study the onset and treatment of childhood behavioral, psychiatric, and developmental disorders. Eligibility: * Individuals of any age who have a psychiatric, autism spectrum, or developmental disorder, or other behavioral problems. * Family members of individuals with the above disorders. This group may include parents, grandparents, siblings, aunts/uncles, cousins, and children. Design: \- Participants will be screened with a medical history and physical exam. They may have a psychiatric history with tests of thinking, judgment, and behavior....