Anxiety Disorders

The primary goal of this clinical trial is to evaluate the unique neural and behavioral effects of a one-session training combining emotion regulation skills training, with excitatory repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (dlPFC). The secondary aim is to identify key changes in the emotion regulation neural network following the combined intervention versus each of the components alone. The third aim is to explore personalized biomarkers for response to emotion regulation training.

Participants will undergo brain imaging while engaging in an emotional regulation task. Participants will be randomly assigned to learn one of two emotion regulation skills. Participants will be reminded of recent stressors and will undergo different types of neurostimulation, targeted using fMRI (functional MRI) results. Participants who may practice their emotion regulation skills during neurostimulation in a one-time session. Following this training, participants will undergo another fMRI and an exit interview to assess for immediate neural and behavioral changes. Measures of emotion regulation will be assessed at a one week and a one month follow up visit.

Digital mental health interventions are a cost-effective and efficient approach to expanding the accessibility and impact of psychological treatments; however, little guidance exists for selecting the most effective program for a given individual. In the proposed study, decision rules will develop for selecting the digital program that is most likely to be the optimal intervention for each user. These treatment recommendations can be implemented in the context of large healthcare delivery systems to improve the delivery of digital mental health interventions at scale.

The overarching aim of the current study is to better understand for whom and how leading digital interventions work in a large healthcare setting. The study builds on the existing literature and follows expert recommendations by using machine learning (ML) methods to develop precision treatment rules (PTRs) for three leading digital interventions for emotional disorders (e.g., anxiety, depression, and related mental health disorders). Specifically, ML methods will be used to develop PTRs to optimize clinical outcomes and associated intervention engagement. This study will leverage a unique partnership between Boston University (BU), SilverCloud Health (SC)--a leading provider of digital mental health care--and Kaiser Permanente (KP)--one of America's leading health care providers.

A clinical trial (RCT) will be conducted to evaluate the relative effectiveness of three distinct empirically supported digital mental health interventions (from SC's existing library of programs) in a sample recruited from KP primary care and other clinical settings. Data from this trial will be used to develop theoretically and empirically informed, reliable selection algorithms for managing treatment delivery decisions. Algorithms will be validated in a separate "holdout" dataset by examining whether allocation to predicted optimal treatment is associated with superior outcomes compared to allocation to a non-optimal treatment. The role of user engagement will be determined, and other mechanisms in treatment outcome.

Using a Hybrid Type 1 Effectiveness-Implementation randomized control trial (RCT) design, the investigators will test the effectiveness of a bundled behavioral activation and medication optimization in reducing symptoms of depression and anxiety in older adults undergoing oncologic surgery (compared with usual care), while examining implementation outcomes.

This study is being conducted together by researchers at the University of Pennsylvania and Lyssn.io, Inc., ("Lyssn"), a technology start-up developing digital tools to support evidence-based psychotherapies (EBPs) for mental health disorders and addiction. This study will implement a technology to assess and enhance the quality of EBPs like Cognitive Behavioral Therapy (CBT) that includes a user interface geared to clinical, supervision, and administrative workflows and needs, and then assess this technology for effectiveness in comparison to usual care.

There is a tremendous global burden of mental illness: Over 50 million American adults have a diagnosable mental health disorder, and major depression on its own is the leading cause of disability worldwide. In the face of this burden, clinical research has documented a variety of effective EBPs (e.g. CBT), and these psychotherapies are utilized on a massive scale. Systems have invested over $2 billion in training providers in specific EBPs. Once trained, however, therapists' adherence to the EBP, also called fidelity, is both crucial for effectiveness and difficult to assess. There is no scalable method to assess the fidelity and quality of EBPs in community practice settings. This is a foundational problem for healthcare systems.

Advances in speech processing and machine learning make technology a promising solution to this problem. The use of technology - instead of humans - to evaluate EBPs means that objective, performance-based feedback can be provided quickly, efficiently, cost-effectively, and without human error. If successful, the present research will be among the first examples of a method for building, monitoring, and assessing the quality of therapy that can scale up to large, real-world healthcare settings.

In this study, the investigators will implement an existing, fully-functional prototype (LyssnCBT) that includes a user interface geared to community mental health (CMH) clinical, supervision, and administrative workflows and needs, and then assess for effectiveness of psychotherapy supported by LyssnCBT in comparison to usual care.

This study will implement LyssnCBT in 5 community mental health agencies, beginning with a single-arm pilot field trial to identify and address any specific barriers to implementing the tool in a community mental health context. The study team will then conduct a larger study in community mental health agencies comparing LyssnCBT to services as usual.

The purpose of this research is to better understand how emotion processing unfolds in the brain using stereoelectroencephalography (sEEG) and direct brain stimulation. This study will use standard behavioral emotion processing tasks combined with neural recording and direct brain stimulation to assess different aspects of emotion processing. Stimulation pulses during pre and post-test periods will assess the effects of stimulation before and after conditioning, the results of which will be combined with results from the activity of each electrode during the emotion tasks to inform us of the nature of emotion processing in the brain and allow us to devise brain modulation protocols in the future.

This Hybrid 1 Study will test the effectiveness of a bundled intervention comprised of behavioral activation and medication optimization in reducing symptoms of depression and anxiety in older adults undergoing Orthopedic surgery (compared with usual care), while examining implementation outcomes.

This study will identify components for inclusion in a coping intervention package to reduce mental health problems among children exposed to high interparental conflict after parental separation/divorce. Reappraisal, distraction, and relaxation coping strategies are related to fewer mental health problems among children, making intervention components based on these strategies key candidates for inclusion in an optimized coping intervention. The primary aim is to experimentally assess the main and interactive effects of three digital intervention coping components (reappraisal, distraction, relaxation) on children's coping efficacy, emotional security, and internalizing and externalizing problems. Secondary aims are to assess indirect effects of the intervention components on children's coping efficacy, emotional security, and internalizing and externalizing problems through their cognitive, emotional, and behavioral reactions to post-separation/divorce interparental conflict events.

The overall aim of this program of research is to improve the mental health of people who identify as LGBTQ+ by increasing their social support through a brief intervention. The purpose of the proposed project is to establish the effectiveness of our empirically-supported, brief acceptance-based behavioral therapy (ABBT). To achieve the specific aims, the investigators will conduct a fully-powered, randomized clinical trial (n=240) with two treatment arms: treatment-as-usual (TAU) vs. ABBT.

Approximately 200 Participants with mild-to-moderate, untreated depression and/or anxiety will be randomly assigned (by chance, like flipping a coin) to 1 of 3 study groups: Lumen Coached Problem-Solving Treatment (PST) (n=100), Human Coached PST (n=50), and optional (delayed) Lumen Coached PST as waitlist control (n=50) to improve emotional health. All participants will complete assessments at baseline and at 18 weeks post randomization.

Depending on the group assignment the PST program will be delivered by Lumen, a virtual voice-based coach on a study iPad, or by a human coach in person for the first session and then via videoconference or phone for the remaining 7 sessions. Participants assigned to the waitlist control group can receive the Lumen coached PST on a study iPad after completing their 18-week follow-up assessment.

Participants will receive 8 coaching sessions to learn problem-solving skills and work on unresolved problems in daily living that may be interfering with their emotional well-being and contributing to depression and anxiety symptoms.

Meru Health Inc. seeks to further validate the Meru Health Program (MHP) as a single solution to screening, referral, and treatment in primary care as compared to treatment as usual using a Randomized Controlled Trial (RCT) study design. The goal of this study is to determine the feasibility, effectiveness, and implementability of this digital mental health (DMH) solution.

If proven effective and implementable, more widely integrating the MHP into primary care has the potential to improve the systems of screening, referral, and treatment for depression nationwide. This, in turn, will serve as a solution to improve access to effective care for the millions of Americans currently suffering from depression, ultimately reducing its public health burden.

This Hybrid 1 Study will test the effectiveness of a bundled intervention comprised of behavioral activation and medication optimization in reducing symptoms of depression and anxiety in older adults undergoing cardiac surgery (compared with usual care), while examining implementation outcomes.

Anxiety-, obsessive-compulsive and trauma- and stressor-related disorders reflect a significant public health problem. This study is designed to evaluate the predictive power of a novel biomarker based on a CO2 challenge, thus addressing the central question "can this easy-to-administer assay aid clinicians in deciding whether or not to initiate exposure-based therapy?"

Anxiety disorders are the most common form of psychopathology, and frequently begin in childhood, resulting in lifelong impairment. Increased brain activity after making mistakes, as reflected by the error-related negativity (ERN), is observed in people with anxiety disorders, even before disorder onset. The ERN is therefore of great interest as a potentially modifiable risk factor for anxiety. However, methodological issues can make the ERN difficult to measure.

Increased brain activity in response to a balance disturbance, as reflected by the balance N1, resembles the ERN, but does not share its methodological issues. The investigators' preliminary data demonstrate that the balance N1 and the ERN are associated in amplitude in adults, suggesting they may depend on the same brain processes. The balance N1 has never been investigated in individuals with anxiety disorders, but it increases in amplitude within individuals under anxiety-inducing environmental contexts. Further, balance and anxiety are related in terms of brain anatomy, daily behavior, disorder presentation, and response to treatment.

The present investigation will measure the ERN and the balance N1 in children (ages 9-12) with anxiety disorders, and further, how these brain activity measures change in response to a brief, 45-minute, computerized psychosocial intervention that was developed to reduce reactivity to errors, and has been shown to reduce the ERN. The investigators will recruit approximately 80 children with anxiety disorders, half of whom will be randomly assigned to the active intervention condition. The other half will be assigned to an active control condition, consisting of a different 45-minute computerized presentation. Participants assigned to the control condition can access the computerized intervention after participation in the study.

The purpose of this investigation is to test the hypothesis that the balance N1 and the ERN will be reduced to a similar extent after the intervention, to demonstrate that these brain responses arise from shared brain processes. Transfer of the effect of the psycho-social intervention to the balance N1 would provide insight into prior work demonstrating that balance training can alleviate anxiety in young children, and well-documented benefits of psychotherapy to balance disorders. Collectively, these data may guide the development of multidisciplinary interventions for the prevention and treatment of anxiety disorders in children.

The purpose of this study is to expand Adhere.ly- a simple, HIPAA-compliant, web-based platform to help therapists engage clients in practicing therapeutic skills between sessions (homework) during mental health treatment by conducting a trial comparing standard therapy to therapy enhanced with Adhere.ly.

This study will compare two behavioral interventions for hoarding disorder in older adults.

The purpose of this research study is to test how a medication called nabilone (Cesamet) affects neurocognitive processes involved in obsessive-compulsive disorder (OCD), including threat response, processing of fear signals, and habitual behavior. OCD is a disabling illness that affects around 2% of the population and involves recurrent intrusive thoughts (obsessions) and repetitive behaviors (compulsions) that lead to distress and/or impaired functioning. Nabilone is a synthetic form of delta-9-tetrahydrocannabinol (THC, the primary psychoactive component of the cannabis plant). It acts on the brain's endocannabinoid system, which has been hypothesized to play a role in OCD symptoms. Nabilone is approved by the FDA for the treatment of chemotherapy-induced nausea and vomiting. It is not FDA-approved for treating OCD.

In this study, 60 adults with OCD will receive a single dose of either nabilone or placebo. Participants will then complete a series of assessments including neuroimaging, psychophysiology (e.g., skin conductance recording), computerized behavioral tasks, and self-report measures. The information gained from this study could contribute to the development of new treatments for people with OCD and related disorders.

University of California, Los Angeles researchers will recruit healthy participants and anxious participants (those diagnosed with social anxiety disorder) age 18-55 years old to participate in a study examining whether the ability of social support figure reminders to prevent the acquisition of fear in healthy participants extends to those with anxiety disorders.

After being recruited from the UCLA community (healthy participants, n = 50) or referred by treatment providers at the Anxiety and Depression Research Center at UCLA (anxious participants, n =50) and undergoing a telephone screening and in-person screening, 100 participants will be enrolled in the study. During the experiment, all participants will undergo the same procedures: undergoing fear acquisition procedures--the repeated pairing of a neutral image with a mild electric shock that ultimately leads to the association of threat of shock with the image--in the presence of an image of a social support figure (provided by participants) and an image of a smiling stranger.

University of California, Los Angeles researchers will recruit healthy participants and anxious participants (those diagnosed with social anxiety disorder) age 18-55 years old to participate in a study examining whether the ability of social support figure reminders to enhance the extinction of fear in healthy participants extends to those with anxiety disorders.

After being recruited from the UCLA community (healthy participants, n = 50) or referred by treatment providers at the Anxiety and Depression Research Center at UCLA (anxious participants, n = 50) and undergoing a telephone screening and in-person screening, 100 participants will be enrolled in the study, with an expected recruited 150 to reach this number. During the experiment, all participants will undergo the same procedures: undergoing a fear extinction procedure in which threatening cues--cues that predict electric shock--will be paired with either an image of a social support figure (provided by participants) or an image of a smiling stranger. These pairings will be presented repeatedly in the absence of shock in order for fear extinction to occur. Participants will return for a follow-up test to determine if fear extinction was successful.

According to the local guidelines (Recommendation for General Practitioners), the first choice Anti-Depressant (AD) in Major Depressive Disorder (MDD) in primary care should be selective serotonin reuptake inhibitors (SSRI), e.g. citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, in depression with anxiety and insomnia is preferable trazodone and in severer disorders mirtazapine. Despite all these molecules have a very good antidepressant effect, there are differences in side effect scale and tolerability.

The aim of this Study is describing of real treatment practice and MDD management in primary care - aimed to evaluate effectiveness of the treatments in depression and related symptoms: insomnia, anxiety, anhedonia and sexual dysfunction.

The primary objective of the Study is to describe the diagnostic process and treatment patterns in MDD- treatment of choice (pharmacologic with details of first choice antidepressant) in the office of GP's.

The secondary objective is to evaluate efficiency of the treatments in depression and related symptoms: insomnia, anxiety, anhedonia and sexual dysfunction and to monitor the type of side effects and comedication during the 8-weeks treatment.

Deep brain stimulation (DBS) is an effective treatment for people suffering from severe obsessive-compulsive disorder (OCD) whose symptoms have failed to improve after years and multiple methods of intervention. An effective DBS target for OCD is the anterior limb of the internal capsule (ALIC) brain region. On average 60% of all OCD patients have a clinically significant response to ALIC DBS. However, ALIC DBS may become even more effective with the ability to predict which specific ALIC connections in the brain need to be stimulated for each individual OCD patient. This study therefore investigates personalized stimulation to the ALIC that allows for precise modulation of brain circuits associated with individual OCD symptoms. The study aims to specify the ideal anatomical target for ALIC DBS for maximum therapeutic benefit in each patient.

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.

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.

Several lines of evidence suggest that unhealthy sleep patterns contribute to depressive symptoms through disruption of brain networks that regulate emotional functions. However, we do not yet know to what degree the emotion regulation brain network is modified by the restoration of sleep, or whether the degree to which a sleep intervention modifies these neural targets mediates reductions in other depressive symptoms including suicidality.

The overall aim is to test the efficacy of an established sleep intervention (Cognitive Behavioral Therapy for Insomnia (CBT-I)) in reducing depressive symptoms through improving emotion regulation brain function in individuals with elevated depressive symptoms and clinically meaningful sleep disturbance.

In this study, we will assess feasibility of recruitment and retention as well as target engagement. Target engagement is defined as the treatment effect on increasing mPFC-amygala connectivity, and/or decreasing amygdala reactivity during emotion reactivity and regulation paradigms. Participants will be 70 adults experiencing at least moderate sleep disturbances and who also have elevated anxious and/or depressive symptoms. Emotion distress and sleep disruption will be assessed prior to, and weekly while receiving six Cognitive Behavioral Therapy for Insomnia (CBT-I) across a period of 8 weeks. CBT-I improves sleep patterns through a combination of sleep restriction, stimulus control, mindfulness training, cognitive therapy targeting dysfunctional beliefs about sleep, and sleep hygiene education. Using fMRI scanning, emotion regulation network neural targets will be assayed prior to and following completion of CBT-I treatment.

The investigators are conducting this study to learn more about the cognitive and attentional processes among individuals with three types of repetitive negative thinking (RNT): mental rituals (as seen in obsessive compulsive disorder, OCD), worries (as seen in generalized anxiety disorder, GAD), and ruminations (as seen in major depressive disorder, MDD). Specifically, the investigators are studying whether psychological treatment can help people with RNT who have trouble stopping unwanted thoughts and shifting their attention.

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.

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.

This project seeks to identify causal neural mechanisms underlying unwanted, repetitive behaviors (compulsions). Using non-invasive brain stimulation coupled with practice in a computer task, we will modulate activity in a target brain region and measure effects on compulsive behaviors and related measures. This work could ultimately lead to the ability to treat compulsions more effectively by targeting the regions of the brain that can help or hinder attempts to overcome compulsions.

Depression and anxiety disorders rank in the top ten causes of years lived with disability. Less than 50% of patients experiencing long-lasting improvements to current gold-standard treatments. Two gold-standard behavioral interventions include behavioral activation, focused on enhancing approach behavior towards meaningful activities, and exposure-based therapy, focused on decreasing avoidance and challenging negative expectations. While these interventions have divergent treatment targets, there is little knowledge to inform which strategies should be used in the frequent case of comorbid anxiety and depression. Approach-avoidance decision-making paradigms focus on assessing responses when faced with potential rewards and threats, tapping into processes important for both anxiety and depression as well as behavioral activation and exposure-based therapy.

For this study, investigators will recruit individuals reporting both anxiety and depression symptoms and randomize them to one of three different interventions: (1) behavioral activation, (2) exposure-based therapy, and a non-specific therapy approach (3) supportive therapy. Participants will complete clinical, self-report, behavioral, and functional magnetic resonance imaging (fMRI) assessments before and after therapy. Investigators will use a computational approach to model factors that may influence one's behavior during approach-avoidance decision-making, including drives to avoid threat versus approach reward and confidence versus uncertainty in one's decisions.

This project will accomplish the following aims (1) Determine how changes in brain and behavior responses during approach-avoidance conflict relate to changes in mental health symptoms with the different therapy approaches, (2) Determine the degree to which baseline brain and behavior responses during approach-avoidance conflict predict response to the different therapy approaches, above and beyond the influence of demographics and baseline symptom severity. In addition, by including peripheral blood draws and measures of grace matter volume, the project will also accomplish the following aims: (1) Determine whether kynrenine metabolites measures peripherally may be beneficial as a biomarker of treatment response and (2) determine whether there is an association between change in kynurenine metabolites and changes in gray matter volume with treatment.

Results will enhance understanding of how different psychotherapy approaches (behavioral activation, exposure-based therapy) may impact brain responses and decisions when faces with potential reward versus threat and approach versus avoidance drives. In addition, results will have important implications concerning the potential for a more personalized approach to psychotherapy, enhancing knowledge of which types of therapy strategies may be most beneficial for which individuals.

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.

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.

The proposed randomized, double-blind research study will use functional magnetic resonance neuroimaging using state-of-the-art HCP acquisition protocols and analytic pipelines, to identify predictors and correlates of response to an accepted first-line pharmacological treatment for obsessive-compulsive disorder.

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.

This study will use magnetic resonance imaging (MRI) to assess the function and structure of overlapping task control circuits in children with a range of Obsessive-Compulsive symptoms (OCS). The functioning of task control circuits will be assessed using the well-validated Multisource interference task (MSIT). This study will also assess functional and anatomical connectivity within task control circuits in the same children, and determine whether disturbances in these overlapping circuits are associated with Obsessive-Compulsive Disorder (OCD) symptom severity. Behavioral measures will be administered to further assess regulatory, learning and memory functions. Children with OCD will then be offered a standard course of up to 12 cognitive behavioral therapy (CBT), either via remote video conference sessions or in person visits when clinically indicated, before scanning (along with age-and gender-matched control participants) in order to assess how these circuits may change with treatment. Children with subclinical OC symptoms will be offered referral for treatment on an as-needed basis. In addition, de-identified data may be used in the future to conduct secondary data analyses. As more about OC symptoms and neurobiological mechanisms of interest in the current study are understood, data may be used to answer questions beyond those described in this protocol. All study procedures will be conducted on-site at Columbia University/the New York State Psychiatric Institute (New York, NY) and the University of Michigan's outpatient Child and Adolescent Psychiatry (Ann Arbor, Michigan).

The purpose of this study is to examine the brain functioning of children and adolescent with OCD before and after treatment with Exposure and Response Prevention (EXRP) therapy.

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:

"<TAB>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.

"<TAB>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.

The NIH grant has funded the development of a physiological brain atlas registry that will allow us to significantly improve the data collectioin and use of physiological data into a normalized brain volume. This initially was used to improve DBS implants for Parkinson's Disease, Dystonia, Essential Tremor, and OCD, but now includes data acquired during all stereotactic brain procedures.

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.

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.