Anxiety & Depression Association of America

Depression is one of the most common disorders of mental health, affecting 7-8% of the population and causing tremendous disability to afflicted individuals and economic burden to society. In order to optimize existing treatments and develop improved ones, the investigators need a deeper understanding of the mechanistic basis of this complex disorder. Previous work in this area has made important progress but has two main limitations. (1) Most studies have used non-invasive and therefore imprecise measures of brain activity. (2) Black box modeling used to link neural activity to behavior remain difficult to interpret, and although sometimes successful in describing activity within certain contexts, may not generalize to new situations, provide mechanistic insight, or efficiently guide therapeutic interventions. To overcome these challenges, the investigators combine precise intracranial neural recordings in humans with a suite of new eXplainable Artificial Intelligence (XAI) approaches. The investigators have assembled a team of experimentalists and computational experts with combined experience sufficient for this task. Our unique dataset comprises two groups of subjects: the Epilepsy Cohort consists of patients with refractory epilepsy undergoing intracranial seizure monitoring, and the Depression Cohort consists of subjects in an NIH/BRAIN-funded research trial of deep brain stimulation for treatment-resistant depression (TRD). As a whole, this dataset provides precise, spatiotemporally resolved human intracranial recording and stimulation data across a wide dynamic range of depression severity. Our Aims apply a progressive approach to modeling and manipulating brain-behavior relationships. Aim 1 seeks to identify features of neural activity associated with mood states. Beginning with current state-of-the-art AI models and then uses a "ladder" approach to bridge to models of increasing expressiveness while imposing mechanistically explainable structure. Whereas Aim 1 focuses on self-reported mood level as the behavioral index of interest, Aim 2 uses an alternative approach of focusing on measurable neurobiological features inspired by the Research Domain Criteria (RDoC). These features, such as reward sensitivity, loss aversion, executive attention, etc. are extracted from behavioral task performance using a novel "inverse rational control" XAI approach. Relating these measures to neural activity patterns provides additional mechanistic and normative understanding of the neurobiology of depression. Aim 3 uses recurrent neural networks to model the consequences of richly varied patterns of multi-site intracranial stimulation on neural activity. Then employing an innovative "inception loop" XAI approach to derive stimulation strategies for open- and closed-loop control that can drive the neural system towards a desired, healthier state. If successful, this project would enhance our understanding of the pathophysiology of depression and improve neuromodulatory treatment strategies. This can also be applied to a host of other neurological and psychiatric disorders, taking an important step towards XAI-guided precision neuroscience.

Type: Interventional

Start Date: Jul 2023

open study

The investigators will screen all mechanically ventilated ED patients for study eligibility and will enroll all consecutive patients satisfying inclusion and exclusion criteria. The study design is a pragmatic, multicenter, stepped wedge cluster randomized trial, enrolling at five sites over a 3-year period, divided into six time periods of six months. Prior to the study, each site will be randomized to their position within the design. One site will cross to the intervention period (i.e. succinylcholine as default neuromuscular blocker) every six months from the 2nd to 6th time period. Cluster order will be determined by computer-based randomization. To begin, each site will be exposed to control conditions; by the end of the study, each site will be exposed to intervention conditions. Patients in the control phase will receive usual care, and this phase will be entirely observational. After six months, a site will enter a 2-month transition phase. In this phase, the investigators will implement the intervention, similar to how they have implemented other ED-based interventions for mechanically ventilated patients. The investigators will engage and educate ED clinicians on the importance of AWP prevention and the study objectives. The intervention framework relies on the use of "nudges", without restricting choice. The use of neuromuscular blockers (i.e. "paralytic" medications) is already part of routine care in the ED in order to facilitate endotracheal intubation and initiation of mechanical ventilation for patients with acute respiratory failure. The two most common neuromuscular blockers used in the ED are succinylcholine and rocuronium. The preliminary data show a strong association between rocuronium (a longer-acting neuromuscular blocker) use and AWP. Therefore, this study aims to improve care by educating caregivers on AWP and the use of the neuromuscular blockers, which are already routinely used, and studying that process in a rigorous fashion. The default neuromuscular blocker in the intervention phase will be succinylcholine. Succinylcholine will be the default over rocuronium because: 1) it has safely been the default neuromuscular blocker of choice in the ED for >40 years ; 2) its 5-minute duration of action greatly reduces AWP risk; 3) the preliminary data regarding an increased risk of AWP with rocuronium and 4) ED rocuronium use has increased despite no patient-centered studies showing benefit over succinylcholine. Passive alerts (i.e. graphics, pocket cards) will also be strategically placed in the ED, and active alerts will be used as reminders before every nursing shift (i.e. "the huddle"). After this transition phase, the site will begin the intervention phase, and patients will again receive clinician-directed care, just after the intervention.

Type: Interventional

Start Date: Jun 2023

open study

Low income women of childbearing age are at increased risk for depression and often do not receive needed treatment. Investigators developed Mom-Net, an on-line cognitive behavioral treatment (CBT) for depression to address the needs of low income women of childbearing age. The intervention program also includes live coaching to help the mothers engage and learn the CBT material. Mom-Net has been shown to be highly effective in reducing depressive symptoms and improving parenting behavior and child adjustment, in earlier controlled trials. In this project the investigators are examining whether access to Mom-Net can be expanded by delivering it in Head Starts (HS). To address that broad question, the investigators will focus on two sets of scientific questions: 1. Implementation Questions: e.g., Can HS agencies deliver the program successfully; do HSs choose to sustain the program after the research project ends; what agency characteristics are associated with successful delivery of Mom-Net); 2. Effectiveness Questions: e.g., Does Mom-Net reduce maternal depression when delivered by Head Start agencies, with HS staff doing the coaching? Head Start agencies will be randomized to deliver either Mom-Net with the usual high-intensity coaching or with a low-intensity coaching alternative. Within each agency, depressed mothers will be randomized to receive either: 1) Mom-Net program; or 2) Treatment as Usual (TAU;) referral to community mental health providers). Mothers initially assigned to the TAU condition, will have the option of receiving Mom-Net at a later date. Mothers will participate in assessments of depressive symptoms, parenting behavior, and child adjustment at Time 1 (T1; prior to randomization); and Time 2 (T2; after the intervention period) and Time 3 (T3; one year after T1).

Type: Interventional

Start Date: Dec 2022

open study

The purpose of this study is to examine whether cerebellar stimulation can be used to improve cognitive deficits and mood in patients with schizophrenia, autism, bipolar disorder, Parkinson's disease, and major depression.

Type: Interventional

Start Date: Nov 2017

open study

"Scanxiety" is a term coined to describe anxiety related to imaging during cancer treatment and has not been robustly studied in pediatric oncology caregivers. Mindfulness-based Stress Reduction (MBSR) is a meditation-based program that offers a non-pharmacologic approach to managing stress. The main purposes of this study are two-fold: 1). to determine if scanxiety exists in the caregivers of pediatric oncology patients and 2.) if scanxiety is found, does the implementation of a mindfulness program help to improve caregiver anxiety related to imaging.

Type: Interventional

Start Date: Feb 2026

open study

The purpose of this research is to understand how changes in RNA editing relate to treatment response in unipolar and bipolar depression.

Type: Interventional

Start Date: Feb 2026

open study

Approximately one third of individuals with Major Depressive Disorder (MDD) are considered treatment-resistant, subject to severe disability and risk of suicide, and exhibit symptoms anchored in abnormalities of Research Domain Criteria (RDoC) Negative Valence Systems behavioral processes. In the present study we plan to use low-intensity focused ultrasound in 120 persons with treatment-resistant MDD to modulate deep white matter tracts connecting the thalamus and different regions of the prefrontal cortex reversibly and non-invasively, with the aim of assigning a causal, mechanistic role to large scale brain circuits in the production of those critical behavioral abnormalities. A successful study will help to attain the precise definition of neuromodulation targets for this clinical population in utter need of help.

Type: Interventional

Start Date: Sep 2025

open study

This study will evaluate the usability, feasibility, and acceptability of a novel multi-level Just-In-Time Training (JITT) implementation strategy (JITT-EBP) that aims to equip mentors and mentor supervisors to implement evidence-based practices (EBPs) with fidelity using methods that are sustainable in rural communities. JITT-EBP integrates (a) self-directed, on-demand, online training modules for mentors and mentor supervisors, (b) synchronous evidence-based supervision strategies, and (c) an apprenticeship delivery model in which EBPs are co-led by an experienced mentor and a novice mentor, providing opportunity for in-the-moment training and support. The study will conduct a pilot hybrid type 2 effectiveness-implementation trial to evaluate the use of JITT-EBP compared to usual training for implementing mentor-delivered Interpersonal Psychotherapy-Adolescent Skills Training (IPT-AST), an evidence-based depression prevention program. 96 adolescents (age 12-17) and their parents, 8-18 mentors (depending on amount of turnover), and 4 mentor supervisors will be enrolled in the trial.

Type: Interventional

Start Date: Dec 2025

open study

This research study is testing whether Mindfulness-Based Stress Reduction (MBSR) can help reduce fatigue in people with sarcoidosis. The study will also look at whether MBSR can improve symptoms of anxiety and depression. Participants will be placed into one of two groups: - One group will take part in an 8-week virtual MBSR program, attend weekly online sessions, keep a daily mindfulness journal, and complete surveys about fatigue, anxiety, and depression. - The other group will join a virtual support group once a month for 5 months and complete the same surveys. The goal is to see which approach is more helpful for improving fatigue and mental well-being in people with sarcoidosis.

Type: Interventional

Start Date: Feb 2026

open study

The purpose of this study is to determine the efficacy, safety and tolerability of CYB003 compared to matching placebo as adjunctive treatment in patients with MDD.

Type: Interventional

Start Date: Dec 2025

open study

The purpose of this study is to perform a comprehensive research assessment of children and adolescents who meet The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) criteria for Bipolar Disorder (BD) , offspring of a parent with BD, and healthy controls (HC), to obtain blood samples and saliva samples from each subject to allow the evaluation for BD biomarkers and genetic information, to notify participants about future research studies they may qualify for , to recommend follow-up with an outpatient provider if needed and to use magnetic resonance imaging (MRI) (structural MRI and diffusion tensor imaging) to investigate brain structures and relevant pathways associated with mood and behavioral regulation, conversion from softer forms of the BD spectrum (BD-NOS) to harder forms (BD-I and BD-II) and possible early identification.

Type: Observational [Patient Registry]

Start Date: Dec 2022

open study

This study is being done to see if nitrous oxide during vasectomy decreases pain and anxiety, and also assess whether patients have better satisfaction when they control their own level of nitrous oxide during the procedure. If we find that patients experience less pain or anxiety with nitrous oxide, it could be suggested that self-adjusted nitrous oxide (SANO) may be a useful tool for improving experience of care during vasectomy.

Type: Interventional

Start Date: May 2023

open study

Repetitive transcranial magnetic stimulation (rTMS) is a FDA-approved treatment for depression and Obsessive Compulsive Disorder (OCD). The goal of the study is to learn how to optimize the treatment to improve symptoms of depression and OCD. This research project will test a new accelerated 5-day accelerated rTMS protocol for treating symptoms of depression and OCD. A second goal of this study is to identify biomarkers of depression and OCD in the brain using functional magnetic resonance imaging (fMRI). This approach will predict who will benefit from TMS, determine the optimal treatment target, and improve treatment outcomes. Subjects will receive a clinical assessment of symptoms and an fMRI brain scan before and after each treatment course to measure the effect of treatment on symptom severity and on fMRI measures of functional connectivity. Participants will be randomized to receive rTMS targeting either the lateral prefrontal cortex (LPFC) or the dorsomedial prefrontal cortex (DMPFC). Participants will complete a 5-day course of rTMS delivered hourly for 10 hours per day. Participants who show a partial response to treatment but not a full response will then receive a second 5-day course. Treatment non-responders will be crossed over to receive rTMS targeting the opposite brain area. The primary hypothesis is that accelerated rTMS treatment will yield rapid improvement in symptoms for patients with depression and OCD in just 5 days, and that response rates can be further improved by adding a second 5-day treatment course.

Type: Interventional

Start Date: Dec 2021

open study

Mood disorders, such as depression and bipolar disorder, are difficult to treat. One reason is that there are no objective ways to measure how these disorders affect the body and respond to different treatments. In this study, researchers want to perform tests on people undergoing clinical care for mood disorders. The purpose is to understand the experience of receiving treatment for depression, bipolar disorder, and suicide risk. We also hope that this study will help us to predict which medications will improve thoughts of suicide. People 18 years or older who are receiving treatment for depression, bipolar disorder, or suicide risk may take part in this study. Participants must have also been enrolled in protocol 01-M-0254. This study will be conducted at the NIH Clinical Center in Bethesda, MD. The study typically lasts up to 12 weeks, but may last longer if a participant s treatment continues past that time. Participants will have weekly interviews and questionnaires while they are being treated for their mood disorder. Other tests are optional and include psychological testing, blood draws, sleep tests, and imaging scans. These will be done at the start and the end of research participation.

Type: Observational

Start Date: Sep 2024

open study

People spend approximately one-third of their lives asleep, yet sleep is often underused as an opportunity to support psychological well-being. Contemplative traditions, including Tibetan Dream Yoga, have developed practices that use waking imagination and lucid dreaming to explore perception, awareness, and habitual patterns of thinking. Recent advances in sleep monitoring, dream communication, and lucid dream induction now make it possible to study these practices using scientific methods. This study is a randomized controlled trial designed to examine the feasibility and effects of a Dream-Yoga-inspired intervention compared with an active control condition. The intervention combines waking and dreaming practices that are adapted for individuals without prior experience and delivered using virtual reality-based training and home sleep technology. The program is designed to be scalable and culturally neutral, without requiring prior knowledge of contemplative or religious traditions. The primary goals of the study are to characterize sleep and waking neurophysiology associated with Dream-Yoga-inspired practices and to evaluate whether participation is associated with changes in sleep-related brain activity and cognitive processes. Outcomes include measures of lucid dreaming, sleep physiology, and waking cognitive and perceptual processes. Anxiety will be assessed as an exploratory outcome to examine whether participation may be associated with changes in emotional experience. This study is not designed to provide treatment for anxiety or other clinical conditions. Results from this study will help inform the development of scalable sleep-based mental training approaches and guide future research on the use of dreaming and sleep practices to support psychological health and well-being.

Type: Interventional

Start Date: Jan 2026

open study

With this research investigators hope to begin to understand how rTMS can improve posttraumatic stress disorder (PTSD) symptoms. TMS improves PTSD through two interrelated mechanisms: change in brain limbic system function and change in systemic inflammatory activation. Participants who decide to join this study, will receive ten rTMS treatments. All participants will undergo a 40-minute rTMS procedure with a member of the study team 10 times over 2-4 weeks. Participants will undergo fMRI scans of the head in order to help researchers better understand potential effects of rTMS on brain activity. In addition, participants will be asked to give two breath and blood samples to look for signs of general inflammation.

Type: Interventional

Start Date: Jan 2026

open study

This study aims to compare the effectiveness of a Virtual Reality (VR) application computer simulation [(CS) VR Mindful Meditation App')] versus music relaxation in reducing anxiety and pain in women undergoing breast biopsies. Participants will be randomized into three groups: VR, music relaxation, or standard care. Anxiety and pain will be measured using validated scales, and an optional physiological marker may be collected to assess stress levels. Participants will also be asked about their satisfaction with the intervention received, along with procedure-specific questions.

Type: Interventional

Start Date: Jan 2026

open study

Post-traumatic stress disorder (PTSD) is a highly prevalent and debilitating condition among veterans and active-duty military personnel, with rates as high as 30% in certain combat-exposed populations. Conventional treatments such as prolonged exposure therapy and pharmacotherapy have limited efficacy and high dropout rates, highlighting the need for novel, rapidly effective interventions. Transcranial magnetic stimulation (TMS) has been well established for treatment-resistant depression (TRD). Traditional TMS, which involves 6 to 7 weeks of daily, weekday scalp-targeted treatment, shows open-label response and remission rates of 58.1% and 30%, respectively. However, such protocols may be impractical for military personnel with limited medical leave. A new form of accelerated TMS (aTMS) that involves 10 imaging-guided treatments per day for 5 consecutive days has demonstrated substantial antidepressant benefits within days and response rates of 69% at 1-month follow-up. This protocol has not been tested for PTSD, in part because there was no causally informed brain circuit target. In this study, the investigators will test aTMS for PTSD using a novel PTSD circuit that the investigators have derived.

Type: Interventional

Start Date: Dec 2025

open study

The goal of this pilot study is to test the effectiveness of a novel intervention for teenagers (ages 15-18) with mental health conditions who have been released from an acute care psychiatric facility. The intervention aims to reduce suicidality, depression, anxiety, re-hospitalization, and to improve mental health recovery by using an online recovery education and support program. The current standard of care (SOC) for these patients at discharge includes a discharge plan with a list of their medication(s), anticipated outpatient appointment(s), and corresponding information on when and where to find community resources. The intervention being tested involves the implementation of an online recovery education and support (RES) program, involving one-on-one and small group meetings led by trained teen peers (TPs) and peer support specialists (PSS). Participants will be assigned to either Cohort A or B for 8 weeks. Cohort A will be the intervention group with online access to an RES, TP, and PSS. - Week 1-4: One-on-one meetings with PSS and TP for education and support. Assessments will be completed at week 2 and 4. - Week 5 and 7: one-one meetings with PSS and TP for education and support. - Week 6 and 8: small group meetings with PSS, TP, and other participants. Assessments will be completed during Weeks 6 and 8. Cohort B will be the SOC group with no PSS, TP, or RES. - Weeks 1-4: Weekly check in phone calls with a member of the research team. Assessments will be completed at Weeks 2 and 4. - Weeks 5-8: Check in phone calls with a member of the research team every other week. Assessments will be completed at weeks 6 and8. Data collected from participant assessments, adherence to medication, and re-admittance to a psychiatric facility will be used to compare the intervention to the SOC.

Type: Interventional

Start Date: Nov 2025

open study

The purpose of this study is to assess the clinical correlates of therapeutic precision ketosis in bipolar depression and to evaluate the cardiometabolic correlates associated with therapeutic precision ketosis in bipolar depression.

Type: Interventional

Start Date: Aug 2025

open study

Addiction and trauma exposure are common among the 5.5 million people (1 in 47 adults) in the U.S. who are in prison or under supervision. About 85% of people in prison have a substance use disorder or are there for a drug-related crime, and many have experienced serious trauma before being incarcerated. Posttraumatic stress symptoms (PTSS) are often a result of trauma and are linked to more severe drug use, higher rates of relapse, and increased crime. PTSS and substance use disorder (SUD) each raise the chances of new arrests for people who are justice-involved, showing that addressing trauma and addiction could help reduce repeat offenses and the costs of incarceration. However, treatments for PTSS are rarely available in prisons, and there is little research on whether providing therapy for PTSS in prison can lower drug use, PTSS, or crime after release. The goal of this clinical trial is to see if trauma-focused group therapy (CPT) provided while in prison, can help people after release from prison. The therapy has been adapted for use in prisons (CPT-CJ) and will be compared to trauma focused therapy delivered via a self-help workbook This study will: - test whether a trauma-focused group therapy (CPT-CJ) can reduce post-incarceration drug and alcohol use, mental health issues, and drug-related crime, compared to trauma-focused self-help, - evaluate a strategy called implementation facilitation, which helps support the use of this therapy in prisons, and - measure the cost of the therapies and support strategies to help plan for future expansion. Incarcerated participants (N = 640; 50% female) will be enrolled from ~10 prisons in ~5 states, ensuring variability in population and setting characteristics. They will: - take surveys and answer questions up to 5 times (before starting treatment, right after getting treatment, right before leaving prison, 3 months after leaving prison and 6 months after leaving prison) - complete CPT group therapy or self-help therapy - provide urine samples 3 months and 6 months after leaving prison Prison stakeholders (e.g., prison staff, prison leadership, governmental officials; N = ~15 per site) who will be purposively sampled based on their role in CPT-CJ implementation will also participate in some surveys.

Type: Interventional

Start Date: Jul 2025

open study

Mental health conditions occurring during pregnancy and up to one year postpartum (the perinatal period) occur in 1 in 5 perinatal individuals. To improve mental health care during the perinatal period, this study will implement and compare a health care model of improving mood and anxiety disorder care in practices with a health care-community partnership model. The study will include 32 perinatal care settings across the United States. Half of them will have the health care model, the other half will have the health care-community partnership model. The study is designed to answer the question, "Should states and healthcare systems put resources into a healthcare system approach or a healthcare-community partnership approach to mental health care?" The results of this study will help states and healthcare systems decide how to develop pathways for increasing access to mental health care for pregnant and postpartum individuals.

Type: Interventional

Start Date: Dec 2025

open study

The goal of this mechanistic clinical trial is to examine whether parent-coaching aimed at increasing child positive affect will increase child neural response to reward. The main questions it aims to answer are: Aim 1. Characterize child neural reward response and its relation to maternal socialization of positive emotions at baseline in healthy young children. Aim 2. Evaluate how coaching-related changes in maternal socialization of positive emotion expression contribute to increases in child neural reward response over time. Aim 3. Examine how maternal socialization of positive emotion expression contributes to increases in child neural reward response in the moment. Participating mother-child dyads will be randomized to either 3 sessions of parent coaching of child positive affect or 3 sessions of a general parenting support intervention and neural response to reward and affective behavior will be examined pre and post intervention.

Type: Interventional

Start Date: Oct 2025

open study

This is a multicenter, randomized, double-blind, placebo-controlled study to assess the efficacy, safety, and tolerability of ITI-1284 as monotherapy treatment in patients meeting Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR) criteria for GAD in patients who have had inadequate response to generalized anxiety disorder treatment.

Type: Interventional

Start Date: Nov 2024

open study

Socioeconomically disadvantaged populations with multiple chronic conditions have high rates of nonadherence to essential chronic disease medications after hospital discharge. Medication nonadherence after hospital discharge is significantly associated with increased mortality and higher rates of readmissions and costs among these patients. Major patient-reported barriers to essential medication use after hospital discharge among low-income individuals are related to social determinants of health (SDOH) and include: 1) financial barriers , 2) transportation barriers, and 3) system-level barriers. Although, medication therapy management services are important during care transitions, these services have not proven effective in improving medication adherence after hospital discharge, highlighting a critical need for innovative interventions. The Medication Affordability, Accessibility, and Availability in Care Transitions (Med AAAction) Study will test the effectiveness of a pharmacy-led care transitions intervention versus usual care through a pragmatic randomized controlled trial of 388 Medicaid and uninsured hospital in-patients with MCC from three large healthcare systems in Tennessee. The intervention will involve: 1) medications with zero copay, 2) bedside delivery then home delivery of medications, and 3) care coordination provided by certified pharmacy technicians/health coaches to assist with medication access, medication reconciliation, and rapid and ongoing primary care follow-up. We will examine the impact of the intervention during 12 months on 1) medication adherence (primary outcome) and 2) rapid primary care follow-up, 30-day readmissions, hospitalizations and emergency department visits, and costs. We will conduct key informant interviews to understand patient experience with the acre received during and after care transitions. By examining effectiveness of the intervention on outcomes including medication adherence, health care utilization, costs, and patient experience, this study will provide valuable results to health systems, payers, and policymakers to assist in future implementation and sustainability of the intervention for socioeconomically disadvantaged populations.

Type: Interventional

Start Date: Apr 2024

open study