Clinical Research Directory

Evaluation of Patients With Mood and Anxiety Disorders and Healthy Volunteers

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

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

This study is intended to help develop new MRI imaging techniques for studying mood and anxiety disorders. Researchers believe that depression and anxiety disorders may cause structural and functional changes in the brain. This study will optimize the way MRI scans are collected to look at brain structure and examine how the brain behaves while subjects perform particular tasks. Healthy volunteers and individuals with major depressive disorder may be eligible for this study. Participants undergo magnetic resonance imaging (MRI) and neuropsychological testing. : Individuals will be asked to participate in an MRI study on one of several scanners. The scanner used will measure blood flow in the brain, concentrations of certain chemicals in the brain, or magnetic properties of the brain. The scan may involve They watching a screen presenting images or doing a task in which they respond to pictures or sounds. Participants may be asked to return for additional scans. The study also involves neuropsychological tests, which assess cognitive performance. Often, people with mood disorders have subtle changes in performance on these tests that allow researchers to pinpoint where brain abnormalities occur. Before the tests can be used in patients, they must be validated by using healthy subjects. These tests are presented either orally, in written form, or on a computer.

Exploring the Efficacy of a Breathing Training Intervention in Patients With Emotionally Regulated Sleep Disorders

In recent years, the incidence of sleep disorders, especially insomnia, has been rising. Insomnia can directly lead to damage to patients' daytime functions, such as daytime sleepiness, inattention, etc., affecting people's normal work and life. Insomnia is related to dysfunction of multiple systems such as the cardiovascular and cerebrovascular systems, endocrine systems, digestion and breathing, and plays a vital role in the occurrence and development of chronic diseases. Therefore, insomnia has become an increasingly serious medical and social problem. At the same time, with the development of society, the incidence of mental illness is gradually increasing. Emotional disorders such as anxiety and depression can greatly affect the quality of life and even seriously endanger people's health and life safety. Insomnia is closely related to mood disorders. Insomnia not only increases the patient's risk of depression, but also increases the risk of suicide in young patients. In addition, mood disorders are also closely related to insomnia. Mood disorders such as anxiety and depression will also increase the incidence of insomnia. There are also studies showing that the quality of life of patients with severe depression is related to insomnia. The impact of emotional state on sleep is multidimensional. Meneo summarized various mechanisms by which emotions affect sleep, such as dysfunction of the prefrontal cortex and amygdala, as well as factors such as cognitive behavior. Among these mechanisms, functional imbalance of the autonomic nervous system is considered to be a core link. The autonomic nervous system is mainly composed of two branches: the sympathetic nervous system and the parasympathetic nervous system. On the one hand, under conditions of emotional stress or anxiety, the activity of the sympathetic nervous system is enhanced, leading to physiological reactions such as increased heart rate and blood pressure, thereby increasing alertness and reducing the tendency to sleep. On the other hand, during sleep, the activity of the parasympathetic nervous system is enhanced, especially reflected by increasing the high-frequency component of heart rate variability, which contributes to the improvement of sleep depth and quality. Although the relationship between mood and sleep disorders has been widely recognized, current research on its underlying mechanisms is still limited, and it is difficult to develop effective intervention strategies based on this. As an emerging biological monitoring method, heart-brain co-testing can simultaneously monitor and analyze the activities of the brain and heart, interpret the connection of heart-brain axis functions from a new perspective, help elucidate related physiological activities, provide evidence for determining the mechanism of the impact of emotions on sleep disorders, and improve the accuracy of diagnosis and evaluation of the effectiveness of treatment. The mind-brain testing method plays a vital role in revealing the complex connection between emotions and sleep disorders. It is expected to improve our research on the mechanisms of emotion and sleep disorders, find new ways to intervene, and thereby improve the public's physical and mental health.

Neurostimulation Versus Therapy for Problems With Emotions

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.

Psychobiological Markers to Improve Diagnosis and to Predict Affective Episodes in Bipolar Disorder

This trial has two studies. In study 1, the investigators will explore the relationships between three psychobiological factors (sleep patterns, motor activity, and decision-making ability). The investigators aim to investigate how these factors interact in BD patients. This understanding will facilitate the distinction of BD patients from patients with recurrent depressive disorder (MDD) and healthy controls. In study 2, the investigators will continue following patients with bipolar disorder and use the interplay between the three psychobiological factors to develop early markers of full-blown affective episodes.

Search for Novel Transcranial Magnetic Stimulation (TMS) Targets for Mental Illness

Participants will receive Transcranial Magnetic Stimulation (TMS) at a random location in the left prefrontal cortex, excluding sites that are potentially unsafe. Extensive behavioral testing will be conducted to determine which behaviors are modulated by stimulating which circuits.

Clinical Study Evaluating Pharmacogenomics-informed Pharmacotherapy Versus Dosing as Usual in Psychiatric Disorders

A 24-week, patient- and rater-blinded, two-arm, parallel-group controlled, and multi-centre randomized clinical trial (RCT) to establish the benefits of pharmacogenetics-informed pharmacotherapy versus dosing as usual (DAU) in psychiatric patients suffering from mood, anxiety, or psychotic disorders.

Evaluate the Effects of Long-term Use of Psychotropic Medications on Eye Movement Patterns With the Gaize Device

The study aims to verify if the Gaize ocular device can effectively identify eye movements indicative of prescribed psychotropic medication usage by employing Drug Recognition Expert (DRE) testing protocols within a controlled virtual environment.

Accelerated vs. Conventional Theta Burst Stimulation for Late-life Depression

The purpose of this trial is to compare the treatment efficacy (improvement in depressive symptoms) of accelerated TBS protocol (where participants receive multiple TBS treatments daily) to conventional TBS protocol (where participants receive a single TBS treatment daily) in late life depression. In addition, the study also aims to determine if specific patterns of stimulation are more or less effective. To do this, all participants will receive active treatments, but some of the participants in this study will receive accelerated TBS and some will receive once daily TBS.

Imagery Rescripting in Primary Care

In the current study we aim to investigate the feasibility, acceptability, and effectiveness of ImRs offered by mental health assistants within primary care to reduce depressive symptoms. In a single-case experimental design (SCED) study, the following hypotheses will be tested: 1. ImRs results in a reduction of depressive symptoms compared to baseline, and this reduction lasts up to six months. 2. Patients with complaints of depressive symptoms find ImRs an acceptable form of intervention when offered by mental health assistants within a general practice setting. Participants will wait for 2-4 weeks and then receive 5 sessions of ImRs over a period of 10 weeks. During these sessions, negative memories related to their depressed feelings are rescripted.

An Innovative Master Platform for Clinical Trials in Mood Disorders

Mood disorders such as depression and bipolar disorder affect over 350 million people around the world. While several effective treatments exist, it is often difficult to match the right treatment to an individual person. Repeated efforts to find the right treatment contribute to poor functioning, low quality of life, and prolongs the time it takes to get well. Most areas of medicine are able to use 'biomarkers' or clinical tests, blood tests, or imaging to help diagnose and treat illness. The search for biomarkers in mood disorders is advancing, but one roadblock to progress is the lack of large, standardized studies of mood disorders that are needed to accurately identify biomarkers. The aim of the ENABLE platform is to provide the Canadian neuroscience community a standardized way of collecting biomarker data from individuals with a range of mood disorders symptoms. In addition, this 'master clinical trial platform' framework will provide a pool of participants who can be recruited into biomarker-based clinical trials.

Nitrous Oxide- Suicidal Ideation

Most clinical major depression responds to standard treatments (medication and psychotherapy); however, a significant subset of depressed patients (15-20%) do not respond to these treatments and are referred to as treatment-resistant major depression (TRMD). New treatments for TRMD are needed, and one promising line of research are drugs known as N-methyl-D-aspartate (NMDA) glutamate receptor antagonists. In a recent pilot study, the investigators of this study demonstrated that the NMDA antagonist nitrous oxide is effective in TRMD, reducing depressive symptoms, guilt, and suicidal thinking. To more closely investigate suicidal thinking, this study is designed as a double-blind, randomized, prospective, inpatient trial comparing inhaled nitrous oxide (N2O) plus treatment as usual versus inhaled placebo plus treatment as usual. All unipolar depressed, acutely suicidal inpatients will receive standard treatment for their depression/ suicidal thinking (TAU). Additionally, participants will undergo a maximum of four one hour inhalation sessions as inpatients and 2 booster sessions as outpatients during which they will receive either inhaled nitrous oxide (50% nitrous oxide/50% oxygen = active treatment) or placebo gas (50% nitrogen/50% oxygen). A target total of 50 patients with suicidal ideation and unipolar depression will be enrolled, 25 of whom will be assigned to the TAU control group and 25 of whom will be assigned to the N2O + TAU experimental group.

A Randomized Double-Blind Active-Controlled Crossover Trial of Respiratory-Gated Versus Non-Gated Transcutaneous Auricular Vagus Nerve Stimulation for the Treatment of Motor and Non-Motor Symptoms in Parkinson's Disease

The goal of this clinical trial is to compare the effects of different modes and frequencies of transcutaneous auricular vagus nerve stimulation (taVNS) on motor and non-motor symptoms in people with Parkinson's disease. The main questions it aims to answer are: Which mode and frequency of taVNS is most effective in improving motor or non-motor symptoms? Are there any side effects or safety concerns with different taVNS frequencies? Researchers will compare three types of taVNS: 25 Hz non-expiratory gated, 25 Hz expiratory gated, and 100 Hz expiratory gated stimulation. Participants will: Receive each type of taVNS in three 2-week cycles, with 2-month breaks between cycles Undergo neuropsychological assessments, imaging, eye-tracking, and biological sample collection before and after each cycle.

Investigation of the Antidepressant Effects of (2R,6R)-HNK, an Enhancer of Synaptic Glutamate Release, in Treatment-Resistant Depression

Background: Major depressive disorder (MDD) is a serious mental illness that can put people at risk of self-harm and death. Many drugs are used to treat MDD, but it can take a long time for them to be effective. Researchers want to know if a faster-acting drug, (2R,6R)-hydroxynorketamine (HNK), can better treat the symptoms of MDD. Objective: To test a study drug (HNK) in people with MDD. Eligibility: People aged 18 to 70 years with MDD. They must have had a screening assessment under protocol 01-M-0254. Design: Participants will be tapered off their current MDD drugs over 2 to 5 weeks. They will stay off of the drugs for up to 2 weeks prior to starting the study medication and procedures. They will have a physical exam with blood tests. They will have tests of their heart function, mood, and thinking. They will answer questions about their symptoms. They may choose to have imaging scans and scans of their brain activity. HNK is given through a tube attached to a needle inserted into a vein. Participants will receive infusions on this schedule: They will receive 4 infusions over 2 weeks. They will stay in the clinical center overnight after each infusion or for the duration of the study. They will receive no drugs for 2 to 3 weeks. They will have 4 more infusions over 2 weeks, with overnight stays after each or for the duration of the study. One set of 4 infusions will be the HNK. The other set of 4 infusions will be a placebo. A placebo looks just like the real drug but contains no medicine. Participants will not know when they are getting the HNK or placebo. ...

Integrated Care for Older Adults With Major Depression and Physical Multimorbidity - The I-CONNECT

The goal of this clinical trial is to learn if I-CONNECT (Integrated Care for Older Adults with Major Depression and Physical Multimorbidity) can improve the health and well-being of older adults with depression or bipolar disorder and at least two chronic physical conditions, such as diabetes or high blood pressure. It will also study if the care model improves how people experience their care, lowers treatment burden, and how well the program is delivered. Researchers will compare two groups: I-CONNECT group: participants receive care coordination, a personalized care plan, medication review, shared decision-making support, and regular follow-up from a care coordinator working with their GP, psychiatrist, pharmacist, and specialists. Usual care group: participants continue with their normal healthcare from their GP and psychiatrist. Participants will: Receive either I-CONNECT or usual care, depending on their group Complete questionnaires about their mood, quality of life, and care experience Have their healthcare use (emergency visits and hospitalizations) tracked during the study

Investigation of Pathogenic Gut Microbiota Patterns in Anxiety, Depression and Panic Disorders

This study aims to investigate the etiology of anxiety, depression, and panic disorders, providing new evidence and insights into the root causes and effective treatments, potentially offering a novel approach to achieving complete recovery.

Evaluation of a Dietary Supplement Containing Melissa Officinalis Formulated in Phospholipids on Mood Well-being and Cortisol Modulation

This is a randomized, double-blind, placebo-controlled pilot study designed to evaluate the effect of an oral nutritional supplement containing Melissa officinalis formulated in phospholipids on mood and cortisol levels in healthy adults. Participants will be randomly assigned to receive either the active supplement or a placebo daily for 3 weeks. The primary outcome measures include changes in mood well-being, perceived stress, and salivary cortisol levels. The study aims to assess both efficacy and safety of the supplement in modulating stress response and emotional balance.

Cold and Heat Investigation to Lower Levels of Depression

This study will recruit 112 medically healthy adults (aged 18-65) currently experiencing depressive symptoms to be randomized to receive either a single Whole Body Hyperthermia (heat therapy) treatment or a Whole Body Hyperthermia treatment followed by a cold water plunge. Participants will complete a baseline assessment of their depressive symptoms as well as 1-week and 2-week post-treatment followup assessments.

RXWell to Decrease Post-Operative Opioid Use in Total Knee or Hip Arthroplasty

It is envisioned that multipronged benefits from this pilot work for the UPMC ISD and its members. It is expected the RxWell platform to provide the following benefits: expansion of the use of RxWell to all UPMC ISD members providing peri-operative mood management with advantage of improved peri-operative outcomes, improving saving for the UPMC ISD by hastening the recovery and decreased resource utilization, and addition to the high-value care of UPMC with this holistic approach to patient perioperative care

Epidemiology of Sleep-Disordered Breathing in Adults

To characterize the natural history and biologic spectrum of sleep disordered breathing (SDB) and other sleep problems and disorders, and test hypotheses regarding the causes and consequences of SDB and other sleep problems and disorders.

Youth Suicide Risk Factors, Reduction of Suicide Risk Factor in Youth People

The YOU-SURF project is at the forefront of youth suicide prevention, with the goal of integrating multimodal clinical and neurobiological data to comprehensively identify risk factors and the most effective intervention strategies. Suicide is one of the leading causes of death among young people, with particularly alarming incidence rates during adolescence and early adulthood. Suicidal risk is a complex phenomenon, determined by a multiplicity of clinical, environmental, and biological factors. Emerging evidence suggests that information derived from neuroimaging, genetics, and the microbiome may also play a significant role. However, studies conducted to date have not yet adopted a truly multimodal approach that jointly integrates these dimensions in the identification of risk factors for suicide in youth. The YOU-SURF project aims to fill this critical gap. YOU-SURF will also pioneer the use of deep transcranial magnetic stimulation (dTMS), an innovative neuromodulation technique, whose effectiveness in reducing suicidal risk in young people will be assessed within a longitudinal design. Although some preliminary evidence suggests a potential benefit of neuromodulation treatments in this population, the specific effects of dTMS on suicidal risk in youth remain largely unexplored. Furthermore, there is a significant lack of knowledge regarding predictors of response to dTMS in young individuals at risk for self-harming behaviors. The specific objectives of the project are as follows: 1. To identify youth suicide risk factors through the integration of clinical, environmental, neuroimaging, genetic, and microbiome data; 2. To longitudinally evaluate the effectiveness of dTMS in the treatment of young people at risk of suicide; 3. To develop a predictive model based on machine learning techniques, grounded in multimodal data, to estimate the individual response to dTMS in this population. The results of the project will provide a solid scientific basis for the development of personalized prevention and treatment interventions, improving clinical effectiveness and resource allocation in youth mental health services.

Phase II: Engagement and Clinical Impact of the Teleo Virtual Therapy Platform in Clinical Settings

This Phase II trial will examine engagement in telehealth for children undergoing psychotherapy. Specifically, the trial will examine patient engagement in Teleo, a virtual therapy platform specifically designed for psychotherapy with youth, as compared to standard video conferencing.

Unobtrusive Monitoring of Affective Symptoms and Cognition Using Keyboard Dynamics (UnMASCK)

Mood disorders are associated with significant financial and health costs for the United States, partially due to cognitive problems in these patients that can worsen disease course and impair treatment response. This study proposes to use smartphone-based technology to monitor cognitive problems in patients with mood disorders by linking brain network changes with predicted worsening of mood symptoms. The proposed study will provide evidence for using smartphone-based passive sensing as a cost-effective way to predict illness course and treatment response.

Digital Phenotypes for Predicting Depression

This longitudinal study aims to identify and validate digital phenotypes that can predict recurrence of major depressive episodes using passively collected, real-time sensing data from smartphones and wearable devices. Over a 12-month period, 540 participants-including patients with mood disorders and healthy or high-risk controls-will complete five clinical assessments at 3-month intervals, wear a Fitbit device daily, and log daily mood ratings via a mobile app. The study includes the development of AI-based predictive models and the construction of an anonymized wearable big-data repository for mood disorders.