Clinical Research Directory

Study of Neuro-Cognitive Correlates of Pediatric Anxiety Disorders

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. ...

Development of Magnetic Resonance Imaging Techniques for Studying Mood and Anxiety Disorders

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....

Pramipexole to Enhance Social Connections

This study seeks to understand if the medication pramipexole improves social connectedness and functioning in adults (ages 18-50) who experience anxiety or depression. The study plans to enroll 108 participants total across two sites (University of California San Diego and New York State Psychiatric Institute). Pramipexole will be given in a 6-week randomized, double-blind, placebo-controlled trial. Social reward processing will be assessed using measures of brain function (fMRI), behavior, and self-report at baseline and week 6. Knowledge gained from this study will help determine the therapeutic potential of targeting the dopamine system to remediate social disconnection as an anxiety and depression intervention.

Gaze-Contingent Music Therapy Augmentation of CBT for Pediatric Anxiety

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.

Group Transdiagnostic Cognitive Behavioural Therapy for Intolerance of Uncertainty Versus Applied Relaxation

Many people find uncertainty distressing, but for some, it may become overwhelming and drive persistent anxiety, worry, and avoidance. This tendency is called intolerance of uncertainty (IU), and appears across many mental health conditions, including generalised anxiety, social anxiety, depression, and obsessive-compulsive disorder, which is why researchers describe it as a transdiagnostic feature. A type of therapy called Cognitive Behavioural Therapy for Intolerance of Uncertainty (CBT-IU) has been shown to reduce anxiety in previous trials. What remains to be known is how uncertainty changes when targeted directly, and whether the same mechanism applies across diagnoses. IU has mostly been measured using questionnaires, which indicate whether people find uncertainty difficult, but not what is actually happening when they encounter it. Recent research suggests that IU is not a single trait but a set of differences in how people estimate different kinds of uncertainty. Therefore, in addition to standard questionnaires, computer-based tasks will be used to explore an "uncertainty fingerprint" for each participant, capturing different aspects of uncertainty processing in a way that self-report measures cannot. In this study, the investigators are comparing CBT-IU, adapted to work across disorders, against Applied Relaxation. Applied relaxation is a well-established therapy that teaches people to notice and release physical tension but does not focus on uncertainty. Adults with high IU and anxiety symptoms (regardless of formal diagnosis) will be randomly allocated to one of the two 12-session group therapies. The investigators will measure anxiety and IU using standard questionnaires as the primary outcomes. Additionally, cognitive tasks will be used to measure the uncertainty fingerprint before therapy, immediately after, and three months later. The aim is to test whether reductions in IU are specific to CBT-IU rather than shared with an equally credible therapy that does not target uncertainty. Going beyond self-reports, the trial will then begin to resolve which specific aspects of uncertainty processing change, so that future treatments can be more precisely targeted and better matched to each person.

Online Parent Education for Child Anxiety

The investigators are doing this research to test whether parents of children ages 2-7 can better manage their child's anxiety by completing a brief, online, self-guided parent education program. One way to provide anxiety management skills to more children, and to potentially prevent worsening outcomes, is to offer online and self-guided educational programs that parents can complete without a clinician. This randomized trial will evaluate the effects of two brief, online, self-guided parent education programs designed to improve parents' understanding of anxiety and teach parents way to help their children cope with anxiety. Parents will be randomly assigned to one of the three programs. The main aim of the study is to examine whether the parent programs, compared to an educational control reduce parental accommodation of anxiety across a 1-, 4-, and 8-month follow-up period. As a secondary aim, the investigators will explore whether the parent programs reduce children's anxiety symptoms over the 8-month follow-up period. Results will inform the development of a scalable, low-cost model for promoting access to evidence-based treatment to young children.

Quantifying Multi-step Avoidance in Anxiety

This study aims to learn more about avoidance behavior in people with anxiety, using mathematical models of decision-making processes and decoded neural signals of threat imminence. Researchers are investigating anxiety-related behavior and brain function in people with and without anxiety. Investigators are also looking at how behavior and brain function during tasks in the lab relate to avoidance in their daily lives. The investigators will also test whether changing how people avoid things in a behavioral task affects how people avoid things in their everyday life.

Evaluation of Patients With Mood and Anxiety Disorders and Healthy Volunteers

The purpose of this protocol is to allow for the careful screening of patients and healthy volunteers for participation in research protocols in the Experimental Therapeutics and Pathophysiology Lab (ETPB) at the National Institute of Mental Health (NIMH) and for the collection of natural history data. In addition the protocol will allow clinicians to gain more experience in the use of a variety of polysomnographic and high-density EEG recordings. Subjects in this protocol will undergo an evaluation which may include: a psychiatric interview; a diagnostic interview; rating scales; a medical history; a physical exam; brain magnetic resonance imaging (MRI); electroencephalography (EEG); electrocardiography (EKG), magnetoencephalography (MEG); blood, saliva and urine laboratory evaluation; and a request for medical records. Subjects may also be asked to complete questionnaires about attitudes towards research and motivation for research participation. The data collected may also be linked with data from other mood and anxiety disorder protocols (e.g., brain imaging, DNA, psychophysiology tests, treatment studies, etc) for the purposes of better understanding the diagnosis, pathophysiology, and treatment response of patients with mood disorders. Parents of minors will be interviewed. Upon conclusion of the screening process, subjects will either be offered participation in a research protocol and will sign the appropriate informed consent, or will be considered not appropriate for participation in research and will be referred back into the community. The current protocol thus serves as an entry point for individuals with mood or anxiety disorders or healthy volunteers to enter NIMH IRB approved ETPB protocols.

Internet-delivered Cognitive-Behavioral Therapy for Adolescents With Autism and Anxiety

Anxiety is very common in autistic youth. Cognitive behavioral therapy (CBT) is the recommended treatment for both autistic and typically-developing (TD) youth with anxiety, yet most families cannot access CBT due to cost, practicalities of attending in-person treatment sessions, and a shortage of trained providers, especially in rural areas. The goal of this project is to increase access to care for families of autistic adolescents with anxiety through an internet-based treatment model.

Modulating Anxious Coping

This is a study to find out if a device that temporarily alters brain activity (repetitive transcranial magnetic stimulation, rTMS) might be used to change how people with anxiety or related concerns cope with feared or anxiety-producing situations. The study is recruiting people who recently started treatment for anxiety or a related concern. The study involves 3 visits to the Medical University of South Carolina. At the first visit, participants do interviews and surveys asking about anxiety and related concerns, and they also do tasks where they see and react to emotional pictures while their brain activation is measured. At the next two visits, participants receive rTMS, which works by rapidly turning a focused magnetic field on and off repeatedly over the head in a way that passes directly through the hair, scalp, and skull and onto the brain and can temporarily increase brain activity under the magnetic field. After rTMS, participants do two tasks where they see and react to emotional situations while wearing sensors on their hand, arms, face, and head. Each visit in this study is expected to last between 2 - 4 hours. This is not a treatment study, but the study is being conducted with the hope that it will help improve treatment in the future.

Intergenerational Study of War-Affected Youth

War-related violence is a leading driver of mental disorders and illness affecting children in low- and middle-income countries (LMICs). Parents exposed early in life to war-related violence and loss are at risk for mental health problems and may pass risks to their offspring. The study posits that war-related trauma alters the stress-response circuitry in ways that endure into adulthood and affect the next generation. This will be the first investigation in a 20-year longitudinal study to examine mechanisms that link parental war-related trauma exposure and subsequent mental health problems to risk for mental disorders in offspring. This study will extend the first intergenerational study of war in Sub-Saharan Africa (R01HD073349) to focus on children (aged 7-24) born to war-affected parents. Assessments of behavioral and biological indicators of the Research Domain Criteria (RDoC)-linked constructs of self-regulation and stress reactivity will be collected, including autonomic nervous system reactivity, inflammation, and telomere length as well as sophisticated observations of parent-child interactions and synchrony. These measures will be utilized to identify potentially modifiable risk and protective processes both to inform the development of screening tools to identify families at risk for poor child mental health and to be deployed as active ingredients of interventions to reduce transmission of mental health problems to children of war-affected parents. This follow-up study involves the following activities: 1. Pilot to assess measure performance and field test study protocols. 1. Translation and adaptation of newly selected measures 2. Pilot study of new child and adult measures with 36 caregivers and 60 children in a district of Sierra Leone unlinked to participants to test the feasibility and validity of new tools. 2. Fifth wave of data collection from war-affected youth who are now parents and their children aged 7-24. 1. Household tracking and re-enrollment of 145 households that were formerly enrolled in the Longitudinal Study of War-Affected Youth (LSWAY; T1: 2002, T2: 2004, T3: 2008, T4: 2016). 2. Quantitative (full sample) and qualitative (subsample) data collection with 145 households who were enrolled in T4 LSWAY, including war-affected youth who are now parents, their intimate partners, and their children aged 7-24. Through these activities, the investigators will test three overarching hypotheses: 1. Childhood war-related trauma exposure will be associated with mental difficulties (anxiety, depression, post-traumatic stress, disruptions of emotion regulation). 2. Poor mental health in war-affected parents will be associated with emotional and behavioral disruptions in biological offspring. 3. Risk and protective factors across the social ecology may serve as intervention targets to mitigate the effects of parental war-related trauma on behavioral disruptions and stress physiology, both within and across generations.

Resilience in Adolescent Development

RAD is a 10-year natural history, longitudinal, prospective assessment study of a cohort of 2,500 participants (ages 10-24 years) that will help uncover the socio-demographic, lifestyle, clinical, psychological, and neurobiological factors that contribute to resilience among children, adolescents, and young adults at-risk for mood and anxiety disorders. As this is an exploratory study, we will assess a comprehensive panel of carefully selected participant specific parameters, including socio-demographic, life habits, clinical, biological, behavioral, neurophysiological, and neuroimaging. The study is designed to observe and collect factors associated with resilience in a non-invasive fashion; no interventions or treatments will be conducted during the project. Assessments will be conducted up to 4 times per year for up to 10 years, as well as a baseline visit. Study visits will be conducted in person whenever feasible but may be completed by phone/mail/computer, if an in-person visit is not possible.

Threat Interpretation Bias as Cognitive Marker and Treatment Target in Pediatric Anxiety: R33 Phase

Anxiety is chronic, debilitating, and the most common mental health problem across development, costing the U.S. over $42 billion annually. This phased innovation grant will test a symptom-personalized cognitive bias modification for interpretation bias (CBM-I) as a mechanistic intervention to reduce interpretation bias and, subsequently, anxiety, in clinically anxious youth. In this R33 trial, participants will be youth ages 10 to 17 (N=72) with a primary "big three" anxiety disorder (i.e., Generalized, Separation, Social). Youth will be randomly assigned to receive either 16 sessions of personalized CBM-I (the optimal dose identified in the R61 Phase of this study) or equivalent time (four one-hour sessions) over four weeks of a cognitive restructuring (CR), intervention. Both interventions aim to modify threat-focused thinking. Please note that the first phase of the trial (R61: NCT04245501 under NIMH award R61MH121552) has been completed and currently this record summary only reflects the R33 phase.

MOCHA: Embedded Inpatient Mental Health Care for High-Risk Perinatal Patients

Pregnant and postpartum patients hospitalized for medical complications experience high rates of depression, anxiety, and trauma-related symptoms, yet access to timely psychiatric care during obstetric hospitalization is limited. Project MOCHA integrates early mental health screening, trauma-informed psychotherapy, and structured follow-up into routine inpatient maternity care for individuals at elevated clinical risk. This single-arm implementation study examines the feasibility, acceptability, and fidelity of delivering a Collaborative Mental Health Care Program within a high-risk obstetric inpatient setting. The program includes brief inpatient psychotherapy, symptom monitoring, and post-discharge follow-up over three months. Preliminary changes in depression, anxiety, attention-deficit hyperactivity disorder, and posttraumatic stress symptoms will be assessed to inform future effectiveness trials and broader health system integration.

Initial Assessment of the Feasibility and Efficacy of a Scalable Digital CBT for Generalized Anxiety and Associated Health Behaviors in a Cardiovascular Disease Population

The treatment of generalized anxiety disorder (GAD) in an accessible manner represents an unmet need for those with cardiovascular disease (CVD), given that patients with CVD experience numerous barriers for in-person treatment engagement. The research plan for the proposed pilot project will entail: (1) open study of the acceptability of the digital intervention (N=5), followed by (2) recruitment and randomization of 90 individuals with a history of acute CVD events and clinical levels of GAD symptoms to dCBT or a waitlist (Control) condition, using a 1.5:1 allocation (dCBT:Control).

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

This study is a clinical trial that evaluates what drives patient engagement and tests the impact of two strategies-automated motivational push messaging and coach support-to improve engagement with an evidence-based mobile app intervention for depression and/or anxiety.

Therapeutic Writing for Adults Suffering From Chronic Pain and Comorbid Mental Health Disorders

The goal of this observational study is to understand the effects and experiences of therapeutic writing interventions in adult women with chronic pain and co-occurring mental health conditions. The main questions it aims to answer are: Can therapeutic writing help relieve chronic pain and emotional distress? How does writing support emotional processing, regulation, and meaning-making during rehabilitation? Participants will take part in a two-part writing intervention involving: Guided writing exercises that focus on emotional processing, emotion regulation, and creating meaning. Individual interviews after the writing sessions to explore their experiences. The study uses qualitative analysis methods-phenomenology and logotherapy-to better understand how these writing interventions may support recovery, improve well-being, and offer non-pharmacological tools for managing chronic pain and mental health challenges.

Qigong and Multicomponent Exercise in Panic Disorder

Panic disorder is a psychiatric disease characterized by recurrent panic attacks that occur in expected or unexpected situations and create feelings of intense fear, restlessness and discomfort. Panic disorder often has a chronic course, its frequency and severity can be irregular, various physical, mental, and behavioral symptoms can develop, and the quality of life of individuals can decrease significantly. Evidence-based psychotherapy and pharmacotherapy are effective in reducing the symptoms of panic disorder and managing the disorder. However, both of these treatment methods have certain limitations, and approximately one-third of patients do not respond to therapy or the response is not sufficiently effective. Delaying treatment of the disease results in a poor prognosis and more established symptoms. Exercise can be viewed as a low-cost, supportive treatment for relieving symptoms with comparable efficacy to medication and other psychological interventions. Although exercise is recommended for patients with anxiety-panic disorder, there remains uncertainty about whether its effects are sustainable, the type and intensity of exercise required for effective treatment, and thus the effects of qigong and multicomponent exercise on multiple health outcomes in panic disorder. The aim of this study is to examine the effects of Qigong exercise training and multicomponent exercise training on anxiety-panic, balance, mobility, walking, functional strength, physical activity, sleep quality, fatigue, chronic musculoskeletal pain, quality of life and cognition.

Better Sleep in Psychiatric Care - Depression, Anxiety and PTSD

Cognitive Behavioral Therapy (CBT) is treatment of choice for insomnia. Many patients in psychiatric care have sleep problems including insomnia, but are rarely given the choice to participate in CBT to improve their sleep. Patients with PTSD, Anxiety disorders and Depression display high levels of sleep difficulties. Sleep problems are often general, such as insomnia and sleep phase problems. In a previous pilot study, the investigators of the current study developed a CBT protocol that would target sleep problems in this mixed psychiatric population. The basis was CBT for insomnia (CBT-i), but also including techniques that would alleviate sleep phase problems (e.g. the systematic use of light and darkness), and techniques to target more general sleep related problems (e.g. difficulties waking up in the morning), that are also common in psychiatric patients. This treatment was well tolerated and gave large withing-group effects on insomnia severity in the pilot study. In a naturalistic randomized controlled trial, the investigators now evaluate the effects of this psychological treatment on sleep and anxiety and depressive symptoms in patients at the units for Anxiety and Affective disorders and Trauma, Southwest Psychiatry and Northern Stockholm Psychiatry, Stockholm County Council, Sweden.

Managing Anxiety in Pediatric Primary Care (MAPP)

The goal of this clinical trial is to conduct a randomized controlled trial to enhance the capacity of pediatric primary care providers to assist their patients who struggle with anxiety. The study aims to refine and assess the feasibility of the Anxiety Action Plan (AxAP), a brief intervention to reduce pediatric anxiety, delivered by primary care providers (PCPs) in community pediatric primary care clinics. The goal of the AxAP is to enhance the capacity of PCPs to identify and intervene with anxious youth, which will enhance access to care in general and especially in locations with few mental health specialists. PCPs participating in this study will attend a training, administer the intervention to enrolled youth assigned to the MAPP condition, participate in coaching sessions, and fill out study questionnaires. Families participating in this study will complete evaluations with the study team, receive the intervention from their PCP (if assigned to the MAPP condition), and fill out study questionnaires. Researchers will compare the MAPP intervention to Enhanced Usual Care (EUC; consisting of videos, handouts, and other resources for anxiety reduction) to see the differences, if any, in child outcomes.

Transitioning Emotionally and Academically to Middle School Successfully (TEAMSS)

Excessive anxiety is a common problem that severely impairs short and long term academic functioning. The transition to middle school (MS) results in increases in anxiety and decreases in academic functioning. Students with anxiety in particular, due to their vulnerability to school-based stressors, are at risk for social, emotional and academic failure during the transition to MS. Unfortunately, the majority of these students do not get identified. Reducing student anxiety has been associated with improvement in academic functioning. Because the transition to MS is inevitable, targeting students with excessive anxiety will help their adjustment to their new school setting, reducing the need for special education and mental health counseling. No interventions exist to help these students with this transition. This study aims to: (1) develop and assess the feasibility of a brief, multi-component intervention, referred to as TEAMSS, Transitioning Emotionally and Academically to Middle School Successfully, to reduce anxiety and improve academic functioning through the transition to MS using an iterative development process (i.e., expert review, two open trials, and small randomized controlled trial (RCT)); (2) conduct a pilot RCT comparing the preliminary impact of TEAMSS, relative to enhanced usual care (EUC), in improving students' social, behavioral, and academic functioning through the transition to MS; and (3) examine theory-based mediators, predictors, and moderators of TEAMSS and assess intervention costs.

SKY Breath Intervention

Depression is highly debilitating and prevalent among adolescents. Adolescent-onset depression is associated with long, severe, and recurrent episodes that are often not responsive to treatment. There is a dire need to develop novel treatments that are efficient, cost-effective, and tolerant for this population. Sudarshan Kriya Yoga (SKY) is a breath-based meditative practice that entails a sequence of specific breathing techniques to help practitioners achieve a state of calm alertness. It has offered benefits as a therapeutic option for mild-to-moderate depression and anxiety disorders and as an adjunctive treatment in patients with major depressive disorder, but the neurological mechanism of SKY breath intervention is still not fully understood. The goal of this study is to determine the efficacy of SKY breath intervention in treating depressed adolescents and to understand its mechanisms. In this study, thirty depressed adolescents and thirty healthy controls will be recruited to evaluate the efficacy of the 8-week SKY intervention. Assessment for depression and anxiety, salivary cortisol, resting heart rate, blood pressure, and neuroimaging will be collected at the baseline, 4 weeks into SKY intervention (questionnaires only), and post-intervention. This will be the first study to evaluate the potential benefits of of SKY breath intervention as a treatment option for depressed adolescents.

Creating Health Course Study for People With Rheumatological Conditions and Mood Disorders

The goal of this project is to critically evaluate the effectiveness of an online health program designed to improve diet and self-care in patients with rheumatological conditions, including rheumatoid arthritis (RA), Sjogren's syndrome (SS), systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), psoriatic arthritis (PsA), anxiety disorders, depressive disorders and moderate depression. Additionally, investigators will assess the program's effectiveness, as well as the challenges and facilitators involved in using an online wellness program to reduce fatigue and enhance the quality of life in patients suffering from these conditions.

Mindful Self-Compassion for Anxiety Disorders and Depression

The study will compare 8-week Mindful Self-Compassion training, compared to a control group that does not receive the intervention, on anxiety and depression symptom severity in patients with diagnosed anxiety disorders (generalized anxiety disorder, social anxiety disorder, and panic disorder) or major depressive disorder.