Clinical trials

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: \- 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: 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 12 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.

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.

Study Description: This study examines relations between neurocognitive and clinical features of pediatric anxiety disorders. The study uses neuro-cognitive tasks, functional magnetic resonance imaging (fMRI), as well as magneto- and electro-encephalography (M/EEG). Patients will be studied over one year, before and after receiving either one of two standard-of-care treatments: cognitive behavioral therapy (CBT) or fluoxetine, a serotonin reuptake inhibitor (SSRI). Healthy comparisons will be studied at comparable time points. Primary Objectives: To compare healthy youth and symptomatic, medication-free pediatric patients studied prior to receipt of treatment. The study seeks to detect relations between clinical features of anxiety disorders at baseline and a wide range of neurocognitive features associated with attention, memory, and response to motivational stimuli. Secondary Objectives: 1. To document relations between baseline neurocognitive features and response to Cognitive Behavioral Therapy (CBT) or fluoxetine, as defined by the Pediatric Anxiety Rating Scale (PARS) and Clinical Global Improvement (CGI) Scale. 2. To document relations between post-treatment changes in neurocognitive features and anxiety symptoms on the PARS following treatment with Cognitive Behavioral Therapy (CBT) or fluoxetine. 3. To document relations among broad arrays of clinical, cognitive, and neural measures Primary Endpoints: Indices of percent-signal change in hypothesized brain regions, comprising amygdala, striatum, and prefrontal cortex (PFC) for each fMRI and MEG paradigm. Secondary Endpoints: 1. Treatment-response as defined by a continuous measure, the Pediatric Anxiety Rating Scale score (PARS), and a categorial measure, the Clinical Global Improvement (CGI) score. 2. Levels of symptoms and behaviors evoked by tasks that engage attention, memory, and elicit responses to motivational stimuli.

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....

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.

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: 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: 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: 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 12 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....

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: 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

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.

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: 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: 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.

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.

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 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.

Study Description: This study examines relations between neurocognitive and clinical features of pediatric anxiety disorders. The study uses neuro-cognitive tasks, functional magnetic resonance imaging (fMRI), as well as magneto- and electro-encephalography (M/EEG). Patients will be studied over one year, before and after receiving either one of two standard-of-care treatments: cognitive behavioral therapy (CBT) or fluoxetine, a serotonin reuptake inhibitor (SSRI). Healthy comparisons will be studied at comparable time points. Primary Objectives: To compare healthy youth and symptomatic, medication-free pediatric patients studied prior to receipt of treatment. The study seeks to detect relations between clinical features of anxiety disorders at baseline and a wide range of neurocognitive features associated with attention, memory, and response to motivational stimuli. Secondary Objectives: 1. To document relations between baseline neurocognitive features and response to Cognitive Behavioral Therapy (CBT) or fluoxetine, as defined by the Pediatric Anxiety Rating Scale (PARS) and Clinical Global Improvement (CGI) Scale. 2. To document relations between post-treatment changes in neurocognitive features and anxiety symptoms on the PARS following treatment with Cognitive Behavioral Therapy (CBT) or fluoxetine. 3. To document relations among broad arrays of clinical, cognitive, and neural measures Primary Endpoints: Indices of percent-signal change in hypothesized brain regions, comprising amygdala, striatum, and prefrontal cortex (PFC) for each fMRI and MEG paradigm. Secondary Endpoints: 1. Treatment-response as defined by a continuous measure, the Pediatric Anxiety Rating Scale score (PARS), and a categorial measure, the Clinical Global Improvement (CGI) score. 2. Levels of symptoms and behaviors evoked by tasks that engage attention, memory, and elicit responses to motivational stimuli.

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.

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.

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.