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Anxiety Disorders

Anxiety is a normal reaction to stress. It helps one deal with a tense situation in the office, study harder for an exam, keep focused on an important speech. In general, it helps one cope. But when anxiety becomes an excessive, irrational dread of everyday situations, it has become a disabling disorder. 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.

Supporting Our Valued Adolescents Pilot Randomized Controlled Trial

Study Type: Interventional
Start Date: April 17, 2018
Location: Pittsburgh, Pennsylvania
Eligibility: Ages 14–19, Does Not Accept Healthy Volunteers

The purpose of this pilot study is to provide preliminary findings testing the Supporting Our Valued Adolescents (SOVA) intervention, two social media sites (one for adolescents, one for parents) aiming to address negative health beliefs, knowledge about depression or anxiety, parent-adolescent communication, in a moderated online peer community, with the goal of increasing adolescent use of mental health services.

Experiential Training for Community Therapists

Study Type: Interventional
Start Date: March 23, 2018
Location: Philadelphia, Pennsylvania
Eligibility: Ages 18 and Older, Accepts Healthy Volunteers

The primary goal of this study is to evaluate the feasibility and acceptability of employing an experiential training approach that targets community mental health therapists' attitudes toward and use of exposure therapy. In addition to assessing attitudes and use of exposure therapy, the study will evaluate the feasibility of recruitment, randomization, retention, and assessment processes, as well as the acceptability of the experiential training relative to training-as-usual. To assess these outcomes, community therapists will be randomized to experiential training or training-as-usual. A subset of therapists from each arm will also complete qualitative interviews to further assess acceptability of the training approaches. The training-as-usual condition will include a traditional one-day workshop that focuses on principles of exposure and incorporates active learning strategies. The experiential training will include a one-day workshop that teaches principles of exposure and has therapists themselves undergo a one-session phobia treatment for spiders. Therapists in both training conditions will be asked to attend weekly consultation phone calls for a three-month period following the trainings.

Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS)

Study Type: Observational
Start Date: March 20, 2018
Locations: Tucson, Arizona; Stanford, California; Wilmington, Delaware; Tampa, Florida; Bethesda, Maryland; Boston, Massachusetts; Minneapolis, Minnesota; Columbia, Missouri
Eligibility: Ages 3 and Older, Accepts Healthy Volunteers

Background:

PANS is an illness that comes on suddenly in children. The full name is Pediatric Acute-Onset Neuropsychiatric Syndrome. It can cause sudden obsessive-compulsive behaviors. It can also cause children to suddenly restricte their food intake. Researchers want to learn more about children with PANS. They also want to learn more about the illness.

Objective:

To study some disorders of behavior and emotion that start in childhood.

Eligibility:

Children 3 14 years old who have had severe obsessive-compulsive symptoms or food restriction start quickly

Design:

Parents will answer questions. The topics include:

Their child s medical history

Their child s physical and mental health

Their family history. The focus will be on neurodevelopmental and psychiatric conditions. A family tree will be drawn.

Participants will have a physical exam.

Participants may take tests on paper or computer. These will focus on thinking, memory, and behavior.

Participants and parents will give a blood sample.

Participants will have magnetic resonance imaging (MRI). A strong magnetic field and radio waves take pictures of the brain. Participants will lie on a table that slides in and out of a metal scanner.

Participants may have photos or videos taken.

Participants may have other tests. These may include heart tests, sleep tests, and lumbar puncture.

Sponsoring Institute: National Institute of Mental Health

Neuroplasticity in an Extended Amygdala Network as a Target Mechanism for Attention Bias Modification Outcome

Study Type: Interventional
Start Date: December 15, 2017
Location: Marquette, Michigan
Eligibility: Ages 18–37, Accepts Healthy Volunteers

Anxiety disorders are one of the most common psychological disorders. Underlying anxiety is an increased attentional bias to threat, which has been identified as a causal contributor in the development of anxiety. Given this causal relationship, attention bias modification was introduced as a treatment option where anxiety is reduced by training individuals to direct their attention away from threat and thereby decreasing anxiety. Over a decade of research using this approach, called attention bias modification (ABM), suggests that overall the approach is effective in reducing anxiety. Although ABM appears to be a very promising treatment option for anxiety, there are several factors limiting the effectiveness of ABM. These include the recognition of individual-level needs and a known underlying mechanism of action by which ABM is effective. Neuroimaging evidence suggests that attentional bias to visual threat is associated with a network of brain regions including the amygdala, anterior cingulate cortex, and visual cortex. In human participants, experience-dependent neuroplasticity is visible in voxel-based morphometry based measures of gray matter volume following training. Recently, voxel-based morphometry measures of gray matter volume have been linked to dendritic spine density—a known cellular mechanism for learning-related neuroplasticity. Thus, voxel-based morphometry measures are ideally suited to measure learning-related neuroplasticity following attention bias modification. In this proposal participants' level of attentional bias, anxiety, and gray matter volume will be measured before and after completing six weeks of attention bias modification training (N = 50) or attention control training (N= 50). The proposal aims to (1) establish that pre-treatment bias predicts variability in gray matter volume in the extended amygdala and anterior cingulate cortex, (2) assess the extent to which reduced extended amygdala and anterior cingulate cortex gray matter volume following ABM underlies reductions in attentional bias and anxiety, and (3) Establish pre-treatment bias as a predictor of successful ABM as measured by reduced bias, reduced anxiety, and reduced gray matter volume in the extended amygdala and anterior cingulate cortex. Consistent with the objectives of the AREA grant and NIMH's focus on identifying and validating new targets for treatment development that underlie disease mechanisms, the current proposal plans to involve students at a rural primarily undergraduate university in a research project aimed at establishing neuroplasticity in the extended amygdala and anterior cingulate cortex as a target mechanism for ABM training outcome, which could be used to objectively track training-related outcomes in anxiety treatment.

Collaborative Care for Children's Mental Health Problems

Study Type: Interventional
Start Date: August 1, 2017
Location: Tehran, Iran, Islamic Republic of
Eligibility: Ages 5–15, Does Not Accept Healthy Volunteers

Background: Mental health problems cause a disproportionate burden of disability among children and youth compared to adults. Primary care plays an important role in efforts to prevent and intervene early in the course of child and adolescent mental health problems. While research with adults has shown the feasibility of integrating mental health care into primary care settings, there have been few studies among children and youth. Evidence remains lacking that integration is feasible in diverse settings, that it improves outcomes, and that methods can be developed to address the mixed symptoms of emerging child/youth problems and their overlap with developmental and parental disorders.

Goals: The purpose of this project is to test the effectiveness of adding a child/youth mental health component into an existing collaborative care program for adult mental health problems. The work will refine a framework for efficient cultural adaption and tailoring of an existing child/youth primary care mental health intervention and then test whether the tailored intervention results in improved child and parent outcomes. The work will also provide evidence about the mechanisms by which those outcomes are achieved and what factors influence uptake of the child/youth component by general practitioners (GPs). These results should be generalizable to low and middle income countries and to underserved areas of the US where there are minimal child mental health resources and family physicians provide the bulk of medical care for children and youth.

Methods: The planned work involves the adaptation/tailoring process followed by a trial with 45 GPs already engaged in collaborative care for adults; the trial will study adding collaborative care for children ages 5-15. GPs will be randomly assigned in groups to begin 6-month control periods involving child mental health screening and referral. They will then receive child/youth training and begin second 6-month periods of screening plus ongoing coaching and booster sessions and collaborative management. Primary outcomes will be measured by recruiting and following for 6 months two cohorts of children/youth and their parents (one control, one collaborative care). Data collected from GPs, parents, youth, and the collaborative care data system will allow measurement of key factors that determine the program's success in helping children and families.

Effects of SRX246, a Vasopressin Receptor (V1a) Antagonist, on an Experimental Model of Fear and Anxiety in Humans

Study Type: Interventional
Start Date: March 3, 2017
Location: Bethesda, Maryland
Eligibility: Ages 21–50, Accepts Healthy Volunteers

Background:

Arginine vasopressin (AVP) is a hormone made in the body. It can make negative feelings stronger. The way AVP is regulated may be abnormal in people who have mood and anxiety disorders. SRX246 is a new drug that can block a receptor for AVP on brain cells. Researchers want to study how this drug affects the way people respond to threat and anxiety.

Objectives:

To see if the new drug SRX246 affects how people respond to the threat of an unpleasant shock.

Eligibility:

Healthy adults ages 21-50

Design:

Participants will be screened in another protocol.

Participants will have 4 visits over 4 weeks.

At visit 1, participants will have small electrodes taped to their arm to give shocks. Electrodes on the arm, chest, and face will measure sweat, heart rate, and blinking. Participants will hear loud noises and get test shocks for about 15 minutes.

At the other 3 visits, participants will have some or all of these tests:

- Blood and urine tests

- Heart tests

- Suicide screen

At each visit, participants will answer questions about their mood and anxiety. They will identify emotions in pictures. They will have shock testing for 40 minutes: they will hear loud sounds through headphones and get shocks.

Participants will take the study pill 2 times a day for a week after visit 1 and a week after visit 3. One week it will be SRX246. The other week it will be a placebo.

Participants may be contacted daily to remind them to take the medicine.

Participants will have either a follow-up visit or follow-up phone call.

Effects of SRX246 on an Experimental Model of Fear and Anxiety in Humans

Study Type: Interventional
Start Date: February 3, 2017
Location: Bethesda, Maryland
Eligibility: Ages 21–50, Accepts Healthy Volunteers

To determine the effects of SRX246 on fear and anxiety based on fear-potentiated startle in humans. Additionally, the effects of the compound on emotion recognition will be explored.

Effect of Transcranial Magnetic Stimulation to the Dorsolateral Prefrontal Cortex on Anxiety Potentiated Startle

Study Type: Observational
Start Date: January 12, 2017
Location: Bethesda, Maryland
Eligibility: Ages 18–50, Does Not Accept Healthy Volunteers

Background:

Researchers want to better understand brain processes related to fear and anxiety. They want to find out if transcranial magnetic stimulation (TMS), a type of brain stimulation, can reduce anxiety.

Objective:

To see how TMS affects fear and anxiety through memory and attention tasks.

Eligibility:

Healthy people ages 18-50 who are right-handed

Design:

Participants will be screened through another protocol.

Participants in the pilot study will have 1 visit. This includes:

Urine tests

Questionnaires about mood and thinking

Shock and startle workup: Electrodes are taped to the wrists or fingers. Participants will be shocked to find out what level of shock is uncomfortable but tolerable. They will hear loud, sudden noises through headphones.

TMS: A coil is held on the scalp. A magnetic field stimulates the brain. Sometimes they might receive fake TMS. This feels the same as real TMS. They will perform simple tasks. Participants in the main study will have 2 visits within 2 weeks.

The first visit includes:

Urine tests

Questionnaires about mood and thinking

MRI: Participants lie on a table that slides into a scanner. They will be in the scanner about 1 hour. A computer screen in the scanner will tell them to perform simple tasks.

The second visit includes:

Shock and startle workup

TMS

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.

A Study Examining Adolescents With Non-Suicidal Self-Injury

Study Type: Observational
Start Date: August 31, 2016
Location: Minneapolis, Minnesota
Eligibility: Females, Ages 12–16, Accepts Healthy Volunteers

This study will examine longitudinal brain development in young adolescent girls with a history of Non-Suicidal Self-Injury (NSSI). Specifically, three constructs outlined by the the Research Domains Criteria (RDoC) will be examined through self-assessment, MRI, and a cognitive battery.

Mental Health Pathways in Internet Support Groups

Study Type: Interventional
Start Date: June 30, 2016
Location: Pittsburgh, Pennsylvania
Eligibility: Ages 18 and Older, Accepts Healthy Volunteers

People facing serious health threats increasingly use Internet health support communities to obtain informational support, emotional support and other resources. This study introduces software algorithms similar to those used by social media sites to put people in touch with helpful information and social interactions. Participants from the American Cancer Society's Cancer Support Network will have access to this online support group using the default interface that orders content by broad content category and date or with a new interface that highlights communication content and people that match users' interests and needs.

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.

A Hybrid Effectiveness-Implementation Trial of Group CBT in Urban Schools

Study Type: Interventional
Start Date: February 29, 2016
Location: Philadelphia, Pennsylvania
Eligibility: Ages 8–99, Accepts Healthy Volunteers

Unresolved psychological problems, such as anxiety, affect a significant number of our students and interfere with their ability to attend, actively participate, and prosper in school. This project will expand the capacity of selected mental health agencies to provide services in the participating schools through school therapeutic services (STS). The project will provide enhanced training in evidence-based behavioral health interventions to school-based mental health providers. The services will be implemented by STS Bachelor's or Master's level therapists supervised by their mental health agency supervisors (Internal Support), who are in turn supported by the research team (Train-the-Trainer) or external consultants (Train the Trainer+).

Community Study of Outcome Monitoring for Emotional Disorders in Teens

Study Type: Interventional
Start Date: January 31, 2016
Location: West Hartford, Connecticut
Eligibility: Ages 12–18, Does Not Accept Healthy Volunteers

Emotional disorders, including an array of anxiety and depressive syndromes, are the most common psychiatric disorders among adolescents, are highly comorbid, and severely impair the lives of youth and their families. Extant evidence-based therapies target only single disorders or symptom domains, are often not adopted by community mental health center (CMHC) clinicians, and have only modest effect sizes. To improve the clinical outcomes of these youth, the proposed study tests the effectiveness of two novel interventions (a transdiagnostic intervention, the Unified Protocol for the Treatment of Emotional Disorders in Adolescents, and a measurement and feedback system, the Youth Outcomes Questionnaires) relative to usual care in CMHCs.

1/2 A Multi-site Systems Intervention for Unemployed Persons With Social Anxiety

Study Type: Interventional
Start Date: January 31, 2016
Location: Ann Arbor, Michigan
Eligibility: Ages 18–60, Does Not Accept Healthy Volunteers

Social anxiety disorder is a highly prevalent condition that interferes with employment. Prior research indicates that social anxiety disorder interferes with work attainment. This project involves a two-site randomized trial of a community-based cognitive-behavioral intervention to reduce social anxiety and improve employment outcomes among unemployed persons with social anxiety disorder.

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.

Developing a Low-Intensity Primary Care Intervention for Anxiety Disorders (AIM-PC)

Study Type: Interventional
Start Date: September 30, 2015
Location: Pawtucket, Rhode Island
Eligibility: Ages 18 and Older, Does Not Accept Healthy Volunteers

The purpose of the study is to develop a personalized, user-friendly computerized treatment for anxiety disorders linked to primary care. The computerized treatment is a type of Cognitive Bias Modification, which targets attention and interpretation biases known to maintain anxiety disorders.

Neurofunctional Predictors of Escitalopram Treatment Response in Adolescents With Anxiety

Study Type: Interventional
Start Date: May 31, 2015
Location: Cincinnati, Ohio
Eligibility: Ages 12–17, Accepts Healthy Volunteers

Neurofunctional Predictors of Escitalopram Treatment Response in Adolescents with Anxiety. To determine the effects of escitalopram on functional activation patterns during a Continuous Performance Task with Emotional and Neutral Distracters, the CPT-END. To examine baseline functional activity and functional connectivity profiles in the ventrolateral prefrontal cortex as markers of subsequent treatment response to escitalopram in adolescents with generalized anxiety disorder (GAD). To use proton magnetic resonance spectroscopy (1H MRS) to examine glutamatergic and γ-aminobutyric acid (GABA)-related abnormalities in the anterior cingulate in adolescents with GAD as compared to healthy adolescents.

Spatial Context and Fear Learning

Study Type: Observational
Start Date: April 18, 2015
Location: Bethesda, Maryland
Eligibility: Ages 18–50, Accepts Healthy Volunteers

Background:

- Fear is a normal response to a threat. Learning fear can be helpful sometimes. For people with anxiety disorders, fear can be long-lasting and too intense. Researchers want to study how people become fearful of situations. They want to understand how the brain learns when it is helpful to feel fear and when it is not.

Objective:

- To better understand brain processes related to fear and anxiety.

Eligibility:

- Right-handed adults ages 18 50 with generalized anxiety disorder, panic disorder, social anxiety disorder, or post-traumatic stress disorder.

- Right handed volunteers ages 18-50 without psychiatric disorders.

- And free of psychiatric medication for 2 weeks

Design:

- Participants will first be screened under another protocol.

- Participants will play a video game inside a magnetic resonance imaging (MRI) scanner. The scanner is a metal cylinder It is surrounded by a strong magnetic field. Participants will lie on a table that can slide in and out of the scanner. A device called a coil will be placed over the head.

- During the scan, participants may play a virtual reality video game. Game instructions will be explained before they enter the scanner.

- While playing the game, participants will wear 2 electrodes on their fingers. These measure sweat on the skin. They will also have 2 small electrodes attached to the left hand. These can give brief mild electrical shocks.

- Participants will be asked questions when playing the game during the scan.

- Before and after the scan, participants will fill out questionnaires about their emotions. They may complete questionnaires online while at the clinic.

Improving Mental Health Through Integration With Primary Care in Rural Karnataka

Study Type: Interventional
Start Date: February 28, 2015
Location: Bangalore, Karnataka, India
Eligibility: Ages 30 and Older, Does Not Accept Healthy Volunteers

This cluster Randomized Controlled Trial was designed to implement and evaluate the effects of a multi-level intervention designed to integrate mental health treatment into rural primary health clinics in South India using a collaborative care model.

Effectiveness of a Unified Transdiagnostic Treatment in Routine Care

Study Type: Interventional
Start Date: December 31, 2014
Location: Boston, Massachusetts
Eligibility: Ages 18–100, Does Not Accept Healthy Volunteers

The purpose of this study is to examine effectiveness and implementation for the Unified Protocol for the Transdiagnostic Treatment of Emotional Disorders in trauma exposed veterans.

Cognitive Bias Modification for Youth Anxiety

Study Type: Interventional
Start Date: September 30, 2014
Location: Portland, Oregon
Eligibility: Ages 12–17, Does Not Accept Healthy Volunteers

Research in the last fifteen years suggests that anxious individuals selectively attend towards threatening information. Attention modification interventions for internalizing adults have been developed to target cognition at this basic level; these programs have demonstrated initial efficacy in attention bias and anxiety symptom reduction. To date, there have been minimal published studies of attention modification in youths with clinical levels of anxiety.

This study is a large randomized efficacy-effectiveness trial (N = 498) to test the benefit of this low-cost, computerized attention modification intervention (Cognitive Bias Modification (CBM) computer application) for anxiety disorders and symptomatology in youth ages 12 to 17. This trial conducted will compare three intervention arms, all of which include underlying treatment as usual (TAU). The investigators directly test the level of clinical support ("scaffolding") needed to adequately deliver self-administered CBM to anxious youth, a finding that will be key to preparing for future deployment-focused trials. The investigators will compare an attention control version of the CBM program (Arm 1) to two active versions of the CBM intervention that have varying levels of patient clinical support: a self-administered CBM program that participants download and install on their home computers (Self-Administered CBM-only; Arm 2), and the same CBM program paired with an adherence promotion (AP) component delivered via brief telephone calls from study "coaches," including as needed, brief motivational enhancement and/or technical assistance (Self-Administered CBM+AP; Arm 3).

The investigators expect that youth receiving CBM and CBM+AP will have improvement in anxiety symptoms and functioning. The investigators will also complete a cost-effectiveness analysis to examine potential costs offset by this intervention.

Cognitive vs. Emotional Psychopharmacological Manipulations of Fear vs. Anxiety

Study Type: Interventional
Start Date: May 31, 2014
Location: Bethesda, Maryland
Eligibility: Ages 18–50, Does Not Accept Healthy Volunteers

Background:

Stress and anxiety can interfere with how well people perform tasks. But performing a task can sometimes lessen anxiety by distracting people from the stress. Researchers want to examine the interaction between attention and stress. They will use two drugs with different effects on stress and concentration.

Objective:

- To better understand how thinking and emotion affect anxiety and performance. Also, to study the effects of methylphenidate and propranolol on performance.

Eligibility:

- Adults age 18 50.

Design:

- First, participants will be screened with a test in which they hear loud, sudden noises through headphones. Sticky pad electrodes will be placed on the skin under one eye. These electrodes will tell us how sensitive participants are to the noises.

- Second, participants will complete questionnaires about their mood, thinking, and anxiety. They will give a saliva sample. For this, a cotton swab will be placed in their mouth for 2 minutes.

- Third, participants will take a single dose of one of the study pills or a placebo. They will then look at words, shapes, and letters on a computer monitor. They will answer questions about what they remember. They may receive a shock or hear loud noises during the tests.

- For the shocks, small metal disk or sticky pad electrodes will be taped to a wrist or finger. For recording bodily responses, additional electrodes will be placed on the arms, body, and under each eye.

- Blood pressure and pulse will be measured during the tests. More saliva samples will be taken.

- At the end of the study, participants will answer questions about their reaction to the study testing and about any effects they noticed from the study pill.

- After the experiment, participants will be evaluated for effects of the study pill.

Brain Imaging and Computer Games in Children With Either Bipolar Disorder, ADHD, Anxiety or Healthy Controls

Study Type: Observational
Start Date: July 31, 2007
Location: East Providence, Rhode Island
Eligibility: Ages 7–17, Accepts Healthy Volunteers

The purpose of this research is to learn more about how children with mental health problems, including bipolar disorder (BD), attention deficit hyperactivity disorder (ADHD), and generalized anxiety disorder (GAD), differ from children without these problems. The investigators want to understand how these 4 groups of children differ in brain activity, function, and structure.

Family Study of Affective and Anxiety Spectrum Disorders

Study Type: Observational
Start Date: October 30, 2003
Location: Bethesda, Maryland
Eligibility: Ages N/A–60, Accepts Healthy Volunteers

This study will examine how depression, anxiety, and migraine run in families. It will help in defining the risk factors for physical, mental, and health problems-as well as define ways that those problems may be prevented and treated.

A broad range of ages among family members will be included to evaluate the patterns of how these disorders are expressed throughout people's lives. Children of all ages will be included, and those ages 8 to 17 will be interviewed directly.

Assessments will be collected through criteria of the Diagnostic and Statistical Manual of Mental Disorders IV as well as the spectrum, or range, of mood disorders and co-existing conditions. A member of the study team will visit the participants at home or will do an interview by telephone. Participation will take approximately 3 to 4 hours. Children will complete questionnaires given by the research team as well as questionnaires that they will do by themselves. The questions will pertain to the children's health, including physical and mental health and medical history, social relationships, problems, skills, and ways of dealing with important or stressful issues in their lives. These questionnaires will take up to 1 hour to complete.

Health history gathered from adult participants will pertain to height, weight, exercise, and general function. Women will be asked about the use of oral contraceptives, estrogen, and progesterone. In addition, there will be questionnaires on personality and temperamental traits, that is, behavior and impulsiveness. Questions will also involve social intuition, family and other environmental factors, general functioning, and basic demographics such as ethnicity, race, socioeconomic status, marital status, education level, and employment history.

Families enrolled in this phase of the research will be invited to participate in the next phase. There would be follow-up to evaluate the development of mood disorders, subtypes, and syndromes across the lifespan.

The Psychobiology of Childhood Temperament

Study Type: Observational
Start Date: May 12, 2003
Locations: Bethesda, Maryland; College Park, Maryland
Eligibility: Ages N/A–25, Accepts Healthy Volunteers

The purpose of this study is to use brain imaging technology to examine brain changes that occur in children when they are exposed to various kinds of emotional tasks and to determine if these changes are related to the child's temperament.

Studies suggest that the risk for developing mood and anxiety disorders in preschool children may be linked to differences in temperament. The relationship between temperament and risk or resilience may reflect the influences of brain activity on behavior at different stages of childhood development. Behavioral inhibition and mood or anxiety disorders have been linked to disturbances in the circuitry of several areas in the brain. However, the involvement of this circuitry in temperament remains unclear. This study will use functional magnetic resonance imaging (fMRI) to examine the function of different parts of the brain in children who have previously undergone temperament studies and have had their temperaments classified.

Two sets of studies will be performed in the current protocol. A small set of pilot studies will be performed in infants, by staff at the University of Maryland. In terms of the studies among infants, these subjects will initially be contacted by staff at Maryland and then will be seen at the NIH for up to three visits lasting between 4- to 5- hours during the first year of life. These subjects also will undergo visits at the University of Maryland throughout the first year of life.

This study will comprise up to four clinic visits. At Visit 1, children and their parents will meet with study staff individually and together for psychiatric interviews. Children will undergo a physical examination, medical history, a urine drug test, and practice in an fMRI simulator. Saliva samples will be collected from the children and tests will be given to assess stage of puberty, temperament, intelligence, feelings, experiences, and behavior. Other visits include fMRI scans of the brain and other tasks.

Expectation of Unpleasant Events in Anxiety Disorders

Study Type: Observational
Start Date: February 20, 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: Observational
Start Date: October 15, 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.

Evaluation of Patients With Mood and Anxiety Disorders and Healthy Volunteers

Study Type: Observational
Start Date: September 21, 2001
Location: Bethesda, Maryland
Eligibility: Ages 3–99, Accepts 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.

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

Study Type: Observational
Start Date: June 27, 2001
Location: Bethesda, Maryland
Eligibility: Ages 8–40, Accepts Healthy Volunteers

This study uses functional magnetic resonance imaging (fMRI) to learn how the brain functions in adolescents receiving fluoxetine (Prozac) cognitive behavioral therapy (CBT) or interpersonal therapy (IPT) for anxiety or depression in children/adolescents.

All participants will receive interviews to assess how they are doing in general, including general mood, degree of nervousness and behavior. Each participant and one of his or her parents will be interviewed separately and together. Those electing the medication study will also receive a physical examination. Participants are asked to complete tasks involving problem-solving and memory that involve looking at pictures, remembering things, testing reaction times, and making simple choices.

Participants with anxiety or depression will first meet with a psychiatrist or psychologist for two weekly sessions of talk therapy.

Those who remain anxious or depressed after these 2 weeks will have the 3 options based on their choice: 1) treatment with fluoxetine daily for 8 weeks 2) cognitive-behavioral therapy or interpersonal therapy (two kinds of talk therapy) once a week for 8 weeks 3) a random assignment (50% chance) to either placebo or fluoxetine for 8 weeks. In addition, subjects also will be randomly and blindly assigned to receive either an active computer-based training task or an inactive computer-based training task, administered as part of the other,along with their medication or talk -therapy treatment. The active training is thought to help anxiety whereas the inactive training is thought to have no effect. The purpose of this part of the study is to understand the best way to help children and adolescents who are having problems with anxiety. However, more research is needed to find the best way to help such children and adolescents. During and after the 8 weeks of treatment, each participant will complete verbal and written symptom ratings. Blood samples will be drawn for laboratory tests before drug treatment and after it ends.

Those who have not improved by the end of the study will be offered other treatment for 1 to 3 months, and the clinicians will help with finding subsequent aftercare. Those who improve with treatment will continue therapy at NIH until an outside physician is able to assume responsibility for monitoring medication.

FOR MORE INFORMATION REGARDING THIS STUDY CALL THE CORE PHONE NUMBER: 301-496-5645

Effects of Arousal and Stress in Anxiety

Study Type: Observational
Start Date: June 27, 2001
Location: Bethesda, Maryland
Eligibility: Ages 18–50, Accepts Healthy Volunteers

This study has several parts. One part will examine the influence of factors such as personality and past experience on reactions to unpleasant stimuli. Others will examine the effect of personality and emotional and attentional states on learning and memory.

When confronted with fearful or unpleasant events, people can develop fear of specific cues that were associated with these events as well as to the environmental context in which the events occurred via a process called classical conditioning. Classical conditioning has been used to model anxiety disorders, but the relationship between stress and anxiety and conditioned responses remains unclear. This study will examine the relationship between cued conditioning and context conditioning . This study will also explore the acquisition and retention of different types of motor, emotional, and cognitive associative processes during various tasks that range from mildly arousing to stressful.