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Transforming the understanding
and treatment of mental illnesses.

Anxiety Disorders

Feelings of anxiety are an expected part of life that can occur in a variety of contexts, such as when we’re dealing with a problem at work, preparing for a test, or grappling with an important decision. However, when people experience anxiety that lasts for an extended period or worsens over time, they may have an anxiety disorder. The symptoms of an anxiety disorder can interfere with daily activities such as job performance, schoolwork, and relationships. Anxiety disorders include generalized anxiety disorder, panic disorder, social anxiety disorder, and phobia-related disorders. Learn more about anxiety disorders.

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Featured Studies

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

Identifying Decision Making Parameters and Their Neural Correlates, Using Human Neuroimaging, in Healthy Volunteers (HV) and Anxiety Patients (AD).

Study Type: Interventional
Start Date: December 6, 2021
Location: Bethesda, Maryland
Eligibility: Ages 18–50, Accepts Healthy Volunteers

Study Description:

This study has two goals: (1) to identify parameters of interest in decision making in the context of anxiety disorders, using theoretical models (2) and to identify neural correlates of these parameters, using human neuroimaging in healthy volunteers (HV) and anxiety patients (AD). Participants are asked to complete a decision-making task, namely the Multi-armed Bandit Task. The study includes 2 arms: Clinic, Scanner.

Clinic: Participants (HV and AD) are asked to fill out questionnaires and complete the Multi-armed Bandit Task. An electric shock is used as the aversive stimulus. Monetary reward is used as the reward stimulus. Additionally, physiological signals (Heart rate, skin conductance activity, startle) are collected during the course of the task.

In addition, in a pilot study, participants startle responses for varying shock parameters are recorded and analyzed.

Scanner: Participants (HV) are asked to fill out questionnaires and complete the Multi-armed Bandit Task. An electric shock is used as the aversive stimulus. Monetary reward is used as the reward stimulus. Additionally, physiological signals (Heart rate, breathing rate) are collected during the course of the task.


The primary objective of this study is to use theoretical models in healthy volunteers (HV) and patients with an anxiety disorder (AD) to better understand how changes in anxiety are associated with changes in decision making. The neural correlates of these decision-making parameters will be identified using functional imaging. In addition, this study will ascertain whether decision making parameters correlate with certain behavioral measures such as trait and state anxiety using (i) questionnaires, (ii) physiological measures.


The primary endpoint of this study is a significant difference in model derived parameters between experimental manipulations (conditions) and/or population groups. The parameters of interest include: 1) Learning Rate, 2) Exploration parameter, 3) Discount rate, 4) Loss aversion, 5) Inverse Temperature.

The neural correlates of these decision-making parameters will be identified using functional imaging parametric modulation.

The secondary endpoints are a significant correlation between functions of model derived parameters and behavioral and/or physiological measures of anxiety including:

Questionnaire scores Startle Skin conductance

Study Population:

Participants will be males and females, 18 years and older. They must be English-speaking. The study population will include patient and volunteer participants. Number of participants:


Multi-arm Bandit task: 80 (40 HV, 40 AD)

Pilot: 20 HV

TOTAL for clinic study: 100


Multi-arm Bandit task: 40 HV

TOTAL for fMRI: 40 HV


Description of Sites/Facilities Enrolling Participants:

Single-site study at National Institutes of Health

Description of Study Intervention:

Multi-arm Bandit task.

Electric shocks: Electric shocks are used as aversive stimuli. Electric shocks are one of the most efficient ways to induce anxiety in the laboratory. The shocks will be delivered through two disk electrodes located on the forearm or on two fingers

Auditory startle: The startle reflex will be elicited with a 102 dB white noise (40-ms duration) delivered binaurally via headphones.

fMRI: A high-resolution T1-weighted anatomical scan of the whole brain using a magnetization prepared gradient echo sequence (MPRAGE) and the functional scans will be acquired. Participants will be scanned in the 7-Tesla fMRI scanner.

Study Duration:

12 months

Participant Duration:

One outpatient visit

Behavioral Activation and Medication Optimization for Perioperative Mental Health

Study Type: Interventional
Start Date: November 17, 2021
Location: Saint Louis, Missouri
Eligibility: Ages 65 and Older, Does Not Accept Healthy Volunteers

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

Online Training for Addressing Perinatal Depression

Study Type: Interventional
Start Date: August 17, 2021
Location: Leominster, Massachusetts
Eligibility: Ages 18 and Older, Accepts Healthy Volunteers

The study team is developing an e-learning course to train obstetric providers to address perinatal mood and anxiety disorders. The study team will conduct a formative evaluation of the e-learning course with 10 obstetric providers and revise/refine the course based on feedback and then conduct a summative evaluation using a cluster Randomized Controlled Trial (RCT). The three-arm cluster RCT will evaluate the effectiveness of 1) a virtual implementation protocol and e-learning/toolkit as compared to 2) e-learning/toolkit alone as compared to 3) treatment-as-usual. Effectiveness will be evaluated based on rates and quality of care for perinatal mood and anxiety disorders. Using 2:2:1 randomization, the study team will randomize a minimum of 15 to a maximum of 25 obstetric practices into three groups: (1) virtual implementation protocol plus e-learning/toolkit (n=6 to 10); (2) e-learning/toolkit alone (n=6 to 10); and (3) treatment-as-usual (n=3 to 5), which will yield a maximum of 1000 patient charts evaluated for care received from obstetric providers in the randomized practices. Charts from 40 patients per practice will be evaluated at 3 different time points.

Modulating Anxious Coping

Study Type: Interventional
Start Date: July 13, 2021
Location: Charleston, South Carolina
Eligibility: Ages 18–65, Does Not Accept Healthy Volunteers

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.

Kidpower Camp - Structured Games or Playgroup

Study Type: Interventional
Start Date: July 7, 2021
Locations: Ann Arbor, Michigan; East Lansing, Michigan
Eligibility: Ages 48 Months and Older, Does Not Accept Healthy Volunteers

Clinically significant anxiety affects 20% of preschoolers and can become chronic, leading to depression, substance abuse, school-drop out and even suicide. To reduce anxiety and prevent its sequelae, clinically affected children must be effectively treated early. Available interventions for clinically anxious preschoolers are effective for some, but not all children, with as many as 50% of 4-7 year olds continuing to meet criteria for an anxiety disorder after treatment.

This trial aims to help learn how Camp Kidpower, trainings using either structured games or a playgroup, may lower anxiety in preschool age children. Playing these games and learning that kids can do it, can teach kids how to keep going when they are feeling anxious. To find out if Kidpower works by helping kids stay in charge of their behaviors and emotions, the study will look at parts of the brain as well as behaviors related to effortful control and fear, before and after training.

The study hypothesizes that Kidpower will produce greater increases in Error-related negativity (ERN), Interchannel Phase Synchrony (ICPS) and effortful control (EC) behaviors than in the Playgroup control.

A Mobile Health Solution for Homework During CBT

Study Type: Interventional
Start Date: June 10, 2021
Location: Tampa, Florida
Eligibility: Ages 7–17, Does Not Accept Healthy Volunteers

The purpose of this study is to preliminarily evaluate a web-based app to improve provider implementation and patient engagement in homework (i.e., between-session practice of skills learned during therapy) during child mental health treatment by conducting a small-scale feasibility trial in community practice settings comparing Cognitive Behavioral Therapy (CBT) to CBT enhanced with the app.

Parent Key Opinion Leaders to Increase Demand of Effective Treatments for Youth Anxiety

Study Type: Interventional
Start Date: May 3, 2021
Location: Philadelphia, Pennsylvania
Eligibility: Ages 18 and Older, Accepts Healthy Volunteers

Despite research identifying effective treatments for youth anxiety, parents (and other primary caregivers) are unaware that some treatments are more effective than others. This study investigates whether having a local parent key opinion leader co-facilitate an educational outreach presentation on effective treatment for youth anxiety will increase parent demand for evidence-based practices (EBPs). It is hypothesized that participants who receive a presentation co-presented by a key opinion leader will be more likely to have sought cognitive behavioral therapy for their child at the three-month follow up, relative to participants who receive a presentation presented by two researchers.

Stay Connected: Testing an Intervention to Combat COVID-19 Related Social Isolation Among Seattle-area Older Adults

Study Type: Interventional
Start Date: April 6, 2021
Location: Seattle, Washington
Eligibility: Ages 60 and Older, Does Not Accept Healthy Volunteers

This study will use the University of Washington's ALACRITY Center's (UWAC) Discover, Design, Build, & Test (DDBT) method to develop and test an intervention to address the MH health needs of older adults in senior housing who are forced to not only shelter-in-place but cannot have family or other visitors during this time. Older people (those over 60 years in age) are especially vulnerable and are more likely to have severe - even deadly - coronavirus infection than other age groups. These facts led to the need to have older adults socially isolate in order to protect their health; visits with family and friends are limited, and in senior housing (independent, supported and assisted care residences) have limited such visits by family to one person a day. This necessary practice of social distancing, while addressing an important public health crisis, unintentionally creates social isolation and loneliness, another deadly epidemic amongst the older population. Even before COVID-19, social isolation and loneliness was a prominent mental health and social problem in the aged, one that is associated with increases in other chronic conditions, dementia and suicide. Effective interventions for social isolation exist but are difficult to access and may not address all the concerns older adults have about this particular period of social isolation. The purpose of this proposed study is to deploy an adaptation of Behavioral Activation Therapy called Stay Connected to treat depression in older adults. The adaptation will allow activity directors and staff in these settings and senior centers to deliver the therapeutic elements of the intervention (behavioral activation) in the context of social distancing/shelter-in-place policies. Social workers in these settings will oversee the activity director and staff delivery of the intervention. The investigators are working with a variety of senior housing types (HUD certified and private systems) and senior centers in Skagit (rural) and King (urban) counties of WA so that the resulting intervention is not tied to economic levels or access to digital technology.

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

Study Type: Interventional
Start Date: March 1, 2021
Locations: Medellín, $location.state, Colombia; Mexico City, $location.state, Mexico
Eligibility: Ages 18 and Older, Does Not Accept Healthy Volunteers

The aim is to evaluate short term and longer term treatment effects of internet-delivered cognitive behavioral therapy compared to treatment as usual for college students with anxiety and/or depression in low-middle income countries of Latin America.

Assessing Visual Processing in High Anxiety

Study Type: Interventional
Start Date: March 1, 2021
Location: Pittsburgh, Pennsylvania
Eligibility: Ages 18–30, Accepts Healthy Volunteers

High trait anxiety, a stable personality trait, is a risk factor for psychiatric disorders. Individuals with high trait anxiety have difficulty differentiating safety from threat, including visual information like emotional faces. This study aims to characterize visual system function in high trait anxiety. A portion of this study involves an intervention. For the intervention portion, a subset of participants will be asked to return for a lab visit upon completing the first portion of the study (multimodal magnetic resonance imaging (MRI) scan). During this follow up visit, participants will complete a computer task that involves looking at faces and identifying emotions. Participants will complete this task either six months or twelve months after their MRI scan visit. Results from this research have the potential to inform novel therapies that target the visual system in individuals at risk for the development of psychiatric disorders.

BRITEPath- Phase 2

Study Type: Interventional
Start Date: November 5, 2020
Location: Seattle, Washington
Eligibility: Ages 12–26, Does Not Accept Healthy Volunteers

BRITEPath (BP) aims to support co-located mental health clinicians in the development of a high quality, effective, and personalized safety plan for referred patients who screen positive for depression and/or suicidal ideation.

BRITEPath utilizes BRITE, a safety planning and emotion regulation app that is loaded on the patient's smart phone and has previously been shown to be well accepted and to reduce suicide attempts compared to usual care in psychiatric inpatients (HR = 0.49). To support mental health clinicians in the development of effective safety plans, study investigators will develop Guide2Brite (G2B), which provides step-by-step instructions for the mental health clinician on how to populate BRITE onto the patient's smartphone and BRITEBoard, a clinician dashboard that tracks patient symptoms, app use, and rating on helpfulness of different interventions assessed through BRITE.

Happy Mother - Healthy Baby: Supplement Study on Biological Processes Underlying Anxiety During Pregnancy

Study Type: Interventional
Start Date: October 20, 2020
Location: Rawalpindi, $location.state, Pakistan
Eligibility: Ages 18 and Older, Accepts Healthy Volunteers

As a supplement to the ongoing randomized evaluation of the Cognitive Behavioral Therapy (CBT) anxiety prevention intervention in Pakistan (R01-MH111859), the investigators propose to explore potential biological mechanisms (related to inflammation and endocrine functioning) of antenatal anxiety through additional data collection with 300 pregnant women.

Targeting the ERN Computerized Intervention Targeting the Error-related Negativity in Young Children

Study Type: Interventional
Start Date: September 1, 2020
Location: Tallahassee, Florida
Eligibility: Ages 5–7, Accepts Healthy Volunteers

Anxiety disorders are the most common form of psychopathology, frequently begin in childhood, and are often associated with substantial lifelong impairment2. Thus, there is a critical need and opportunity to identify neural markers of risk that distinguish anxious from healthy trajectories early in development that may serve as novel targets for intervention - especially if they are evident before symptoms have become impairing. One promising neural marker of anxiety is increased brain activity in response to mistakes, as reflected by the error-related negativity (ERN). Considering that the ERN is elevated before anxiety symptoms become impairing, it is critical to identify environmental factors that may shape the ERN early in life - so that those factors can be manipulated to reduce the ERN and potentially mitigate risk. In a sample of 295 six-year old children, the investigators found that both observational and self-report measures of harsh parenting style related to an increased ERN in offspring. A similar pattern of results was reported by another lab among 4 year-old children. Moreover, results suggested that the ERN mediated the relationship between harsh parenting and child anxiety disorders.

Based on these data, the investigators propose to develop a novel psychosocial intervention to be administered to both parents and children, which aims to normalize the ERN in children (i.e., reduce over-reactivity to making errors). The proposed Mentored Career Development Award (K01) is designed to extend the investigator's previous work on the ERN, parenting, and risk for anxiety in young children to test the extent to which the ERN can be modulated. Specifically, the investigators will recruit 100 parent/child dyads, high in error sensitivity, and randomize 75 to an intervention condition and 25 to an active control condition. The investigators will measure the ERN in children pre and post intervention, as well as baseline anxiety symptoms. At a six-month follow-up, the investigators will assess children's ERN, as well as anxiety symptoms, to examine to what extent intervention-related changes in the ERN relate to decreases in anxiety symptoms. Moreover, this training plan builds on the investigator's expertise on the ERN and anxiety, and integrates expertise in the design and implementation of computerized interventions, as well as advanced statistical analyses related to intervention outcomes.

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

Study Type: Interventional
Start Date: August 12, 2020
Location: Pittsburgh, Pennsylvania
Eligibility: Ages 16–30, Does Not Accept Healthy Volunteers

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

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

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

Trial to Test Effectiveness of Depression Intervention for Mistreated Older Adults

Study Type: Interventional
Start Date: July 15, 2020
Location: New York, New York
Eligibility: Ages 55–100, Does Not Accept Healthy Volunteers

The investigators developed EM/PROTECT, a behavioral intervention for depressed EM (elderly mistreatment) victims, to work in synergy with EM mistreatment resolution services that provide safety planning, support services, and links to legal services. PROTECT is built on a model which postulates that chronic stress promotes dysfunction of the cognitive control (CCN) and reward networks, impairing the victims' ability to flexibly respond to the environment and limits their reward activities. PROTECT therapists work with victims to develop action plans to reduce stress, and to increase rewarding experiences. EM/PROTECT has been designed in an iterative process with community EM providers of the New York City (NYC) Department for the Aging (DFTA) to use agencies' routine PHQ-9 depression screening and referral for service. In the current study, the investigators will compare the effectiveness of EM/PROTECT with EM enriched with staff training in linking EM victims to community mental health services (EM/MH). The investigators intend to enroll 50 subjects that will participate in the study for approximately 12 weeks.

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

Study Type: Interventional
Start Date: June 20, 2020
Location: Denver, Colorado
Eligibility: Ages 10–17, Does Not Accept Healthy Volunteers

Anxiety is the most common mental health problem in children and adolescents. This two-phased study will test the effects of an experimental computerized intervention aimed at reducing threat-based thinking (i.e., interpretation bias) in anxious youth. Participants in both the R61 (N=46) and R33 (N=72) trials will be youth ages 10 to 17 with a primary anxiety disorder (Separation, Social, Generalized). In the R61 trial, youth will be randomly assigned to receive 16 sessions over 4 weeks of either a personalized cognitive bias modification program for interpretation bias (CBM-I) or a computerized control condition (ICC). If CBM-I reduces interpretation bias significantly more than the ICC, the R33 trial will commence. In the R33, youth will be randomly assigned to either CBM-I or an equal amount of time in a cognitive restructuring intervention, which also aims to reduce threat-based thinking in anxiety.

Transcranial Direct Current Stimulation and Fear Extinction

Study Type: Interventional
Start Date: April 9, 2019
Location: Lexington, Kentucky
Eligibility: Ages 18–55, Accepts Healthy Volunteers

Psychiatric disorders characterized by pathological fear and anxiety are common and often disabling. Despite their limitations, exposure therapies are among the most efficacious treatments for these disorders. Extinction learning is thought to be a core mechanism of therapeutic exposure. Extinction learning is mediated by a well-defined circuit encompassing the medial prefrontal cortex (mPFC), amygdala, and hippocampus. This raises the exciting possibility that direct engagement of this circuitry might enhance the response to therapeutic exposure. Transcranial direct current stimulation (tDCS) is a neuromodulation technology that can augment brain plasticity, learning, and memory. The proposed study will evaluate whether tDCS can engage extinction circuitry, and improve extinction learning and memory.

This study will enroll psychiatrically healthy volunteers to test whether tDCS applied to the mPFC can augment spontaneous mPFC activity, engagement of extinction circuitry during extinction learning and recall, and classically-conditioned extinction learning and memory. Healthy volunteers will complete a standardized, three-day fear conditioning and extinction learning and memory task. On day 1, participants will complete a fear conditioning task. On day 2, participants will receive sham (placebo) or active tDCS prior to completing a fear extinction learning task. On day 3, participants will complete an extinction recall task. Electrodermal activity and heart rate will be continuously monitored during the conditioning and extinction procedures to assess autonomic arousal. All procedures will be completed in a magnetic resonance imaging (MRI) scanner; imaging data will be collected before and after tDCS and during all conditioning and extinction procedures.

Dimensional Brain Behavior Predictors of CBT Outcomes in Pediatric Anxiety

Study Type: Interventional
Start Date: December 31, 2016
Location: Ann Arbor, Michigan
Eligibility: Ages 7–17, Accepts Healthy Volunteers

Anxiety is among the most prevalent, costly and disabling illnesses and tends emerge early in childhood. Cognitive behavioral therapy (CBT) is the first-line treatment for early life anxiety, but as many as 40% of young patients who receive CBT fail to get better. The proposed study will examine brain changes marking positive response to CBT for anxiety and how these changes may differ in children compared adolescents. By helping us to understand how CBT works, this study will pave the way for new treatments to stop anxiety early.

Approach-Avoidance Conflict-a Multi-level Predictor for Therapy Response

Study Type: Interventional
Start Date: June 30, 2016
Location: Tulsa, Oklahoma
Eligibility: Ages 18–55, Does Not Accept Healthy Volunteers

This project aims to identify brain and behavioral characteristics of individuals experiencing symptoms of generalized anxiety disorder that will predict the effectiveness of Exposure-based therapy versus Behavioral Activation Therapy. Brain imaging aspects of the study will use functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). Behavioral assessments will include self-report questionnaires, computer-based and observational tasks, and interviews. Assessments will focus on how individuals process positive information (such as reward) and negative information (such as distressing images), as well as how people make decisions. These assessments will be conducted across 2-3 in-person sessions prior to beginning the treatment, and will be repeated across 2-3 in-person sessions after completing treatment. A blood draw will also be conducted pre- and post- treatment. Both the Exposure-based and Behavior Activation therapy will consist of 10, 90-minute weekly therapy sessions conducted in small groups.

Mechanism of Antidepressant-Related Dysfunctional Arousal in High-Risk Youth

Study Type: Interventional
Start Date: December 31, 2015
Locations: Stanford, California; Cincinnati, Ohio
Eligibility: Ages 12–17, Accepts Healthy Volunteers

A 16-week double blind, placebo-controlled investigation of escitalopram in adolescents with depression and/or anxiety with a family history of Bipolar Disorder. Subjects will be evaluated using semi-structured diagnostic interviews and symptom ratings, participate in a MRI scan and then randomized to treatment. Following randomization, high-risk youth will have visits every week for the first 4 weeks of treatment then biweekly up to 16 weeks during which time tolerability and ratings will be performed. MRI scan will be repeated at week 4.

Neural Basis of Meal Related Interoceptive Dysfunction in Anorexia Nervosa

Study Type: Interventional
Start Date: October 31, 2015
Location: Tulsa, Oklahoma
Eligibility: Ages 18–55, Accepts Healthy Volunteers

This study aims to identify the brain regions responsible for encoding cardiorespiratory 'interoceptive' sensations and determine whether they are dysfunctional in individuals affected by eating disorders, anxiety, depression, or brain injury. By evaluating the same interoceptive sensations across different human illnesses, the investigators hope to provide convergent evidence resulting in identification of core underlying neural processes, and to discern relative contributions in each condition.

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

Study Type: Observational
Start Date: December 6, 2006
Location: Bethesda, Maryland
Eligibility: Ages 18–65, Accepts Healthy Volunteers

This study is intended to help develop new MRI imaging techniques for studying mood and anxiety disorders. Researchers believe that depression and anxiety disorders may cause structural and functional changes in the brain. This study will optimize the way MRI scans are collected to look at brain structure and examine how the brain behaves while subjects perform particular tasks.

Healthy normal subjects between 18 and 50 years of age who have never had a major psychiatric disorder and who have no first-degree relatives with mood disorders may be eligible for this study. Candidates are screened by phone with questions about their psychiatric and medical history, current emotional state and sleep pattern, and family history of psychiatric disorders. Candidates who pass the preliminary screening then undergo additional screening interviews and laboratory tests.

Participants undergo magnetic resonance imaging (MRI) and neuropsychological testing, as follows:

" MRI scans: Subjects are asked to participate in an MRI study on one of several scanners to measure blood flow in the brain, concentrations of certain chemicals in the brain, or magnetic properties of the brain. MRI uses a strong magnet and radio waves to obtain pictures of the brain. The subject lies still on a narrow bed with a metal coil close to the head. For this study, subjects may be asked to wear a special coil on the neck to help measure blood flow. They may be asked to watch a screen presenting images or to do a task in which they respond to pictures or sounds and may be asked to return for additional scans.

" Neuropsychological testing: Subjects may undergo tests of cognitive performance. Often, people with mood disorders have subtle changes in performance on these tests that allow researchers to pinpoint where brain abnormalities occur. Before the tests can be used in patients, they must be validated by using healthy subjects. These tests are presented either orally, in written form, or on a computer.

Expectation of Unpleasant Events in Anxiety Disorders

Study Type: Interventional
Start Date: March 24, 2003
Location: Bethesda, Maryland
Eligibility: Ages 18–50, Accepts Healthy Volunteers

Fear and anxiety are normal responses to a threat. However, anxiety is considered abnormal when the response to the threat is excessive or inappropriate. This study will examine changes in the body and brain that occur during unpleasant learning experiences in healthy volunteers with high, moderate, and low levels of anxiety.

A high degree of generalized anxiety is a component of many anxiety disorders and is regarded as a marker of vulnerability for these disorders. People with anxiety disorders and individuals with high degrees of anxiety have inappropriate expectations of unpleasant events. This study will investigate the development of expecting unpleasant events in healthy volunteers with varying degrees of anxiety using aversive conditioning models. A later phase of the study will enroll participants with anxiety disorders and compare their responses to those of healthy volunteers.

Patients who meet criteria for an anxiety disorder, and healthy volunteers who have no history of psychiatric or major medical illness will be enrolled in this study. Volunteers will come to the NIH Clinical Center three times for outpatient testing.

Brain Changes in Fear

Study Type: Interventional
Start Date: November 4, 2002
Location: Bethesda, Maryland
Eligibility: Ages 18–50, Accepts Healthy Volunteers

The purpose of this study is to use brain imaging technology to investigate brain changes in people exposed to predictable versus unpredictable unpleasant stimuli. Unpleasant events that can be predicted evoke a response of fear, whereas unpredictable, unpleasant stimuli cause chronic anxiety not associated with a specific event. Information gained from this study may help in the development of more effective treatments for anxiety disorders.

When confronted with fearful events, people eventually develop fear of specific cues that were associated with these events as well as to the environmental context in which the fearful event occurred. Evidence suggests that cued fear and contextual fear model different aspects of anxiety. However, studies that examine the way the brain affects expression of contextual fear have not been conducted. This study will use magnetic resonance imaging (MRI) or Magneto-encephalography (MEG) to compare the brain activity underlying fear brought on by predictable and unpredictable aversive stimuli.

Clinical Trial of Fluoxetine in Anxiety and Depression in Children, and Associated Brain Changes

Study Type: Interventional
Start Date: October 2, 2001
Location: Bethesda, Maryland
Eligibility: Ages 8–50, Accepts Healthy Volunteers

Objective: This protocol uses functional magnetic resonance imaging (fMRI) to examine neuro-cognitive correlates of pediatric and adult mood and anxiety disorders. The primary goal of the project is to document, in pediatric anxiety disorders and major depression, perturbations in brain systems mediating attention biases, fear conditioning, emotional memory, and response to various forms of motivational stimuli. As one secondary goal, the project measures the relationship between these factors and treatment response to either fluoxetine, a specific serotonin reuptake inhibitor (SSRI), cognitive behavioral therapy (CBT), or interpersonal psychotherapy (IPT). Another secondary goal examines similar associations in adults.

Study Population: A total of 2530 children, adolescents, and adults will be recruited. Most subjects will not be able to complete all procedures. We seek to comprehensively study 150 juveniles with only a current anxiety disorder, 60 juveniles with current major depression, 150 juveniles with no psychiatric disorder, 100 adults with major depression, 60 adults with an anxiety disorder, and 150 adults with no psychiatric disorder. To achieve this, we are recruiting 2530 individuals.

Design: Subjects will be tested using fMRI paradigms designed to examine brain regions engaged when processing motivationally salient stimuli, as assessed during attention, memory, social interaction, reward, and fear-conditioning paradigms. After these initial fMRI tests, subjects with depression or an anxiety disorder receive treatment. Treatment will comprise open treatment with either fluoxetine or CBT, augmented with computer-based attention retraining, delivered in a randomized-controlled design, with random assignment to either active or placebo attentiontraining regimens. Adolescent subjects then will be re-tested after eight-weeks using only the attention, memory, and conditioning paradigms.

Outcome Measures: Prior imaging studies note that tasks requiring attention modulation, emotional memory, social interchange, and fear conditioning engage brain regions previously implicated in adult mood and anxiety disorders. These regions include most consistently the amygdala and ventral prefrontal cortex. Moreover, imaging studies of reward function implicate the striatum and prefrontal cortex in adult mood disorders. As a result, we hypothesize that attention, memory, social interaction, reward, and conditioning paradigms will engage the amygdala, ventral prefrontal cortex and striatum in both psychiatrically healthy and impaired subjects. Moreover, we hypothesize that these healthy and psychiatrically impaired groups will differ in the degree of engagement.

Juvenile subjects also will be treated for eight-weeks, and a subset will be re-tested with fMRI. We predict that pre-treatment abnormalities in neural circuitry will predict response to treatment, such that increased amygdala and prefrontal activation will occur in individuals who show the strongest response to treatment. Moreover, we hypothesize that effective treatment will normalize abnormalities in attention and emotional memory, as manifest in fMRI.