Clinical trials

Background: PDE4D is a protein found in the brain. It helps control chemical signals that affect mood, memory, and thinking. Problems with PDE4D may play a role in depression and Alzheimer's disease. Being able to measure PDE4D levels in the body would help doctors identify and manage these diseases. Researchers want to find out if a new tracer (a radioactive substance injected during imaging scans) can help them see PDE4D in people more effectively. Objective: To test a new tracer (\[11C\]JMJ-129-d2) 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 01M0254 or 17M0181. Design: All participants will give samples of blood and urine. They will have a test of their heart function. A plastic tube will be inserted into a vein in their arm; the new tracer will be given through this tube. Some participants will have 1 positron emission tomography (PET)/computed tomography (CT) scan of their whole body. They will lie on a padded bed that slides into a doughnut-shaped machine; the machine uses x-rays to create images of the inside of the body. Some participants will have 1 or 2 PET/CT scans of their brain only. Their head will be supported to keep it still during the scan. They will also have a magnetic resonance imaging (MRI) scan of the brain. MRI uses magnetic fields to capture images of the inside of the body. The MRI scan may require a second visit. All participants will receive a follow-up call to check on their well-being 1 to 3 business days after their scans.

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: 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....

Background: Anxiety disorders are becoming more common among children and teenagers. Anxiety can lead to long-term physical and mental problems, such as depression. Treatments for anxiety disorders include medications as well as cognitive behavioral therapy (CBT); CBT is a form of talking therapy. Both approaches work in only about 50 percent of cases. A new approach, called gaze-contingent music reward therapy (GCMRT), may help. Objective: To find out whether GCMRT combined with CBT is more effective than CBT alone. Eligibility: Children aged 8 to 17 years with separation anxiety disorder; generalized anxiety disorder; or social anxiety disorder. They must be enrolled in protocol 01-M-0192. Design: Participants will come to the clinic once a week for 4 weeks for CBT. Sometimes the participant will meet with the doctor alone; sometimes their parent may be present. They will do some computer-based tasks: They may be asked to push a button when a target appears; they may look at pictures of faces while the computer tracks their eye movements. Participants will take questionnaires each week. They will answer questions about their anxiety symptoms, feelings, and behavior. For the next 8 weeks, participants will participate in both CBT and 1 of 2 types of GCMRT. GCMRT is a computer-based task. Participants will look at pictures with many faces in them; while they do this, pleasant music will play and stop playing over a 12-minute period. Participants will have a final visit in week 13. They will take questionnaires. They will do final research tasks. Each visit lasts about 2 hours....

Background: Children with attention deficit hyperactivity disorder (ADHD) often have cognitive problems. It may be hard for them to control their behaviors, concentrate for long periods, or make decisions. This can affect their education, friendships, and daily life. Virtual reality-based games may help improve cognitive skills in children with ADHD. It may also help change how the brain functions. Objective: To see if virtual reality-based games help improve thinking skills and brain function in children with ADHD. Eligibility: Children aged 8 to 16 years with ADHD. Design: We will first do a pilot study, meaning that everyone will receive the games. If this is successful, we will then conduct a randomized controlled trial, meaning that some participants will be randomly assigned to the full version of the games and some will be randomly assigned to a limited version. Participants will be screened. Their physical and mental health, medical and family history, and intellectual and emotional development will be evaluated. They will have tests of their mood, memory, attention, thinking, and behavior. Participants may have an MRI scan of the brain. They may also have magnetoencephalography (MEG) and electroencephalography (EEG) scans, which record brain activity using sensors placed near or on the head. These scans are optional. Participants will receive a set of virtual reality games. The set includes 3 different games all played using a virtual reality headset. The participant will play the games for 20 minutes 5 days a week for 4 weeks. The parent or caregiver will start each game using an iPad. Each of the games is designed to help the participant practice specific cognitive skills. These include inhibition control, processing speed, and working memory. Participants will have interviews each week. They will answer questions about motion sickness, eye strain, headache, and any other side effects, as well as number of game sessions played. The brain scans may be repeated after the last game session. For the pilot, participants will have a final interview at the study end. For the full trial, a 1-month follow-up visit will be done by telehealth.

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: When children have severe irritability and temper outbursts, they can be so cranky or angry that it leads to problems at home, in school, and with friends. This is called Disruptive Mood Dysregulation Disorder (DMDD) and there have been no psychological treatments developed specifically for children with this problem. Researchers think two forms of therapy, Cognitive Behavioral Therapy (CBT) and Interpretation Bias Training (IBT), might help children with DMDD. Objective: To test two whether IBT and CBT can decrease severe irritability in children and youth. Eligibility: Children 8-17 years old with DMDD. Their symptoms must have started before age 10. Design: Participants will be screened with a review of their symptoms. Parents and participants will answer questions. Participants can do only one or both of these treatments if they wish. Those who wish to do both will start with IBT. Participants who do CBT will have 12-16 weekly meetings of research talk therapy. A parent will participate in part of the sessions. Participants will talk about what makes them irritable and how it affects them. They may be put in situations that might make them annoyed or irritable. Participants will rate how intense their irritability is. Parents and participants will complete rating scales, questionnaires, and interviews. Participants will do practice activities at home. Participants doing IBT will have up to 14 sessions over 10 weeks. Participants will view 15 faces, one at a time, on a computer. They will choose if the face looks happy or angry on a computer. Sometimes the computer gives feedback. Participants will complete some sessions at the NIH and some at home. Participants and parents answer questions about their progress.

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.

This study will use magnetic resonance spectroscopy (MRS) to measure in the brain the transfer of \[13\]C as it is naturally metabolized from glucose to specific chemical transmitters. From this method, we can measure the rate of production of an important excitatory neurotransmitter (glutamate) as well as an inhibitory neurotransmitter (GABA)....

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: Making decisions during daily life is a complicated behavior. Even simple choices can be affected by a range of emotions, stresses, and moods. Mental health issues such as depression and anxiety can lead people to make decisions that have negative effects on their lives. Learning how changes in feeling affect a person's decisions may help researchers find ways to help them make more positive choices. Objective: To learn how changes in a person's feelings and emotions affect their decisions. Eligibility: People aged 18 to 55 years who are healthy or who have some level of depressive, anxiety, substance-related, or addictive disorders. Design: All study activities can be done remotely; participants may use a smartphone app, a website, or telehealth. Participants will have a baseline visit. They will complete tasks that require decisions; these tasks are like games they play on their phone. They will also answer questions about their habits, how they feel, their sleep quality, and any problem behaviors. They may wear a smartwatch during the study; it will record data such as their movements and heart rate. For 12 weeks, a study app will prompt participants to respond. They will be asked to answer questions about how they are feeling, any problematic behaviors, or big life events; they will be asked to complete tasks that require making decisions. They may record a video or audio clip describing their day and how they feel. For 3 of the 12 weeks, participants will get prompts up to 6 times per day. For 9 weeks, they will get up to 3 prompts per day. They will have an end-of-study visit to discuss their experiences.

Background: Mood disorders, such as bipolar disorder, can have serious effects on a person s life. People with bipolar disorder are more likely to have heart disease and abuse substances. In this natural history study, researchers would like to learn more about the connection between exercise and mental health in people with and without mood disorders. Objective: To better understand relationships among physical activity, sleep, and mental health. Eligibility: People aged 8 to 60 years with a history of a mood disorder. Healthy spouses and relatives with no mood disorders are also needed. Design: Participants will be in the study up to 2 years. For up to 20 days in a row, at 4 times during the study, participants will: Complete an electronic diary on their smartphone. Participants will answer questions about their mood, health, sleep, and daily activities. Wear an activity monitor, like a wristwatch, that records how much they move. Wear a light sensor, as a necklace, to record the amount of light in their environment. Some participants will do additional tests. Twice during the study, for 3 days in a row, they will: Wear monitors to record their temperature, heart rate, and sleep. Provide saliva samples. Complete cognitive tasks on their smartphone. Participants will visit the NIH clinic 2 times. They will have a physical exam, with blood and urine tests. They will wear a heart monitor. They will ride a stationary bike for 30 minutes. They may have an imaging scan. Some participants will stay overnight. They will go to sleep wearing a cap to measure their brain activity.

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: 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: Major depressive disorder (MDD) is a serious mental illness that can put people at risk of self-harm and death. Many drugs are used to treat MDD, but it can take a long time for them to be effective. Researchers want to know if a faster-acting drug, (2R,6R)-hydroxynorketamine (HNK), can better treat the symptoms of MDD. Objective: To test a study drug (HNK) in people with MDD. Eligibility: People aged 18 to 70 years with MDD. They must have had a screening assessment under protocol 01-M-0254. Design: Participants will be tapered off their current MDD drugs over 2 to 5 weeks. They will stay off of the drugs for up to 2 weeks prior to starting the study medication and procedures. They will have a physical exam with blood tests. They will have tests of their heart function, mood, and thinking. They will answer questions about their symptoms. They may choose to have imaging scans and scans of their brain activity. HNK is given through a tube attached to a needle inserted into a vein. Participants will receive infusions on this schedule: They will receive 4 infusions over 2 weeks. They will stay in the clinical center overnight after each infusion or for the duration of the study. They will receive no drugs for 2 to 3 weeks. They will have 4 more infusions over 2 weeks, with overnight stays after each or for the duration of the study. One set of 4 infusions will be the HNK. The other set of 4 infusions will be a placebo. A placebo looks just like the real drug but contains no medicine. Participants will not know when they are getting the HNK or placebo. ...

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 18-70 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, 3-6 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: \- Little is known about how the brain changes during childhood and adolescence, how genes affect this process, or how the brains of people with 7q11.23 genetic variation change during this period. Researchers are interested in using magnetic resonance imaging to study how the brain changes in healthy children and children with 7q11.23 genetic variation, including Williams syndrome and 7q11.23 duplication syndrome. Objectives: \- To study developmental changes in the brains of healthy children and children who have been diagnosed with Williams syndrome,7q11.23 duplication syndrome, or other 7q11.23 genetic variation. Eligibility: * Healthy children and adolescents between 5 and 17 years of age. * Children and adolescents between 5 and 17 years of age who have been diagnosed with Williams syndrome, 7q11.23 duplication syndrome, or have other 7q11.23 genetic variation. Design: * Participants will have a brief physical examination and tests of memory, attention, concentration, and thinking. Parents will be asked about their child s personality, behavior characteristics, and social interaction and communication skills. * Both participants and their parents may be asked to complete additional questionnaires or take various tests as required for the study. * Participants will have approximately 10 hours of magnetic resonance imaging (MRI) scanning, usually over 4 to 5 days, within a one month period. Some of these tests will require the participants to do specific tasks while inside the MRI scanner. * Participants will be asked to return to the National Institutes of Health clinical center to repeat these procedures every 2 years thereafter until age 18.

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 volunteers and individuals with major depressive disorder may be eligible for this study. Participants undergo magnetic resonance imaging (MRI) and neuropsychological testing. : Individuals will be asked to participate in an MRI study on one of several scanners. The scanner used will measure blood flow in the brain, concentrations of certain chemicals in the brain, or magnetic properties of the brain. The scan may involve They watching a screen presenting images or doing a task in which they respond to pictures or sounds. Participants may be asked to return for additional scans. The study also involves neuropsychological tests, which assess 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.

Background: Negative emotional states can affect a person s behavior as they make decisions. For example, hunger may make people more impatient; they may then make riskier choices. Other negative emotional states that can change behavior include stress, pain, and sadness. By learning more about how emotions affect thinking and behavior in healthy people, researchers hope to better understand how to identify and treat people with mental disorders. Objective: To learn how negative emotions affect the brain and decision-making behavior. Eligibility: Healthy people aged 18 to 55 years. Design: Participants will have 3 clinic visits in 3 weeks. Participants will fill out questionnaires. They will be asked about their personal history, their personality, and state of mind. For 2 visits, participants will be assigned to different groups. Each group will experience 1 type of emotional stressor: Some participants will watch a video. Some will have to do arithmetic problems. Some will have heat applied to an arm or leg. Some will experience cold by immersing their hand in ice water. For a snack craving test, some will be tempted by food after a 4-hour fast. During these tests, participants will have sensors attached to their bodies. They will be videotaped. Saliva samples will be collected. After the stressors, participants will do tasks on a computer. They will need to make choices. Some participants will perform these decision-making tasks while lying in a brain scanner for functional magnetic resonance imaging. The brain scan involves lying on a table that slides into a cylinder that takes images of the brain. ...

Background: -The brain has two systems for recognizing objects. One system recognizes what an object is, and the other system recognizes where the object is located. However, there is much about how the brain handles and interprets the information from these two systems that is still unclear. Researchers want to study the parts of the brain that are involved in how vision is processed. They will use magnetic resonance imaging (MRI) and transcranial magnetic stimulation (TMS) or transcranial electrical stimulation (tES) on the brain. MRI measures what parts of the brain become more active when tasks are performed. TMS uses magnetic pulses to temporarily change the activity in parts of the brain. tES uses electrical current to temporarily change brain function. Objectives: -To better understand how people visually recognize different types of objects. Eligibility: -Healthy volunteers between 18 and 50 years of age, who only speak English. Design: * This study includes many different experiments on vision. Each experiment may combine visual tasks, MRI scans, and TMS or tES. Participants may be asked to have several different tests. Each test will require a separate visit to the National Institutes of Health. * Participants will be screened with a physical exam and medical history. They will have a baseline brain scan at the first visit. * Participants may do visual tasks alone, with MRI only, with TMS or tES only, or with MRI and TMS or tES combined. For the visual tasks, they will look at pictures of objects on a computer screen. Sometimes the images will appear very briefly (less than one-tenth of a second). Sometimes they will appear for up to 5 seconds. These images will be of things like faces, bodies, tools, and scenes. Participants will be asked to respond in different ways to the pictures. They may respond by typing on a computer keyboard or by pressing a button. Participants will have time to practice the tasks before the experiment. * Participants will remain on the study for up to 3 years.

Despite the clear importance of adolescence in the emergence of a number of disease states and processes, there is surprisingly little known about how the endocrine and metabolic events accompanying puberty in humans impact normal developmental neurobiology. Epidemiologic studies have identified sexual dimorphisms in the prevalence of several neuropsychiatric disorders, including depression, schizophrenia, and substance abuse. Many of these sex differences emerge during or shortly after puberty and are maintained until the 5th-6th decade of life. For example, the two-fold greater risk of unipolar depression in women compared with men does not appear until adolescence, and prior to puberty girls are not at increased risk relative to boys. Puberty is a structured, transitional process that can be influenced by both nutritional factors and environmental stressors; nonetheless, the variability in the timing and duration of puberty is largely determined by oligogenic inheritance. Basic neuroscience research has demonstrated that hormonal events accompanying puberty impact on many of the physiologic systems involved in the regulation of brain function (e.g., the appearance of new neurons in a brain-region specific pattern, neuronal remodeling, and the pruning of cortical connectivity). Additionally, not only does stress during puberty increase the risk of disturbances in affective adaptation during adulthood, but the events accompanying puberty modify stress responsivity (e.g., alterations in the duration and peak response of hypothalamic-pituitary-adrenal \[HPA\] axis hormones to stressors). Moreover, animal work has demonstrated that neural connectivity differs in a brain regional specific manner according to the stage of puberty (i.e., early versus late). In humans, puberty also occurs in stages, and although the endocrinology of puberty, surprisingly, has not been fully characterized with longitudinal data, studies have documented that the physical changes measured by Tanner stages I to V are accompanied by progressive increases in the secretions of both gonadal and adrenal steroids. Nonetheless, there remains considerable variability in the timing and duration of this otherwise highly structured reproductive transition. We propose to perform a longitudinal, naturalistic study examining changes in brain structure and function, behavior, and stress responsivity in boys and girls across the pubertal transition. Because the pubertal transition is defined by a complex series of physiologic events that emerge sequentially over several years and involve changes in multiple endocrine and growth systems, and because there is also considerable variability in the timing of these events reflecting the influence of both genetic and environmental factors, puberty cannot by delineated by age of the participants as has been done in most imaging and other neurobiological studies of adolescence. The present study will formally bridge this gap by defining pubertal events per se in participants. Participants will include healthy boys and girls whose pubertal status will be assessed, and in whom endocrine, metabolic, and brain imaging measures will be evaluated at eight - ten month intervals from age eight years (pre-puberty) until age 17 years (post-puberty). Reproductive endocrine, metabolic, and physical measures will be employed to characterize the stage and duration of pubertal development. Outcome measures will be derived via multimodal neuroimaging techniques, cognitive/behavioral assessments, metabolic measurements, and evaluations of HPA axis function. Additionally, the impact of genetic variation on the developmental trajectory of these parameters (both reproductive and CNS) will be determined. This cross-institute proposal will employ a multidisciplinary approach to evaluating the effects on CNS function of the process of puberty in both boys and girls. This work will not only serve to inform research on the mechanisms by which sexual dimorphisms in neuropsychiatric disorders develop, it will also have important implications for the prevention and treatment of these disorders.

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.

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.

Mood disorders, such as depression and bipolar disorder, are difficult to treat. One reason is that there are no objective ways to measure how these disorders affect the body and respond to different treatments. In this study, researchers want to perform tests on people undergoing clinical care for mood disorders. The purpose is to understand the experience of receiving treatment for depression, bipolar disorder, and suicide risk. We also hope that this study will help us to predict which medications will improve thoughts of suicide. People 18 years or older who are receiving treatment for depression, bipolar disorder, or suicide risk may take part in this study. Participants must have also been enrolled in protocol 01-M-0254. This study will be conducted at the NIH Clinical Center in Bethesda, MD. The study typically lasts up to 12 weeks, but may last longer if a participant s treatment continues past that time. Participants will have weekly interviews and questionnaires while they are being treated for their mood disorder. Other tests are optional and include psychological testing, blood draws, sleep tests, and imaging scans. These will be done at the start and the end of research participation.