Clinical trials

The goal of this clinical trial is to learn about cognition in psychotic disorders (schizophrenia, bipolar disorder, and schizoaffective disorder). The main question it aims to answer is: Can we use magnetic stimulation to change processing speed (how quickly people can solve challenging tasks). Participants will be asked to perform cognitive tasks (problem-solving) and undergo brain scans before and after transcranial magnetic stimulation (TMS). TMS is a way to non-invasively change brain activity. Forms of TMS are FDA-approved to treat depression and obsessive compulsive disorder. In this study, we will use a different form of TMS to temporarily change brain activity to observe how that changes speed in problem-solving.

This is a randomized, controlled clinical trial to assess the effects of the ketogenic diet in combination with treatment as usual on brain energy metabolism and psychiatric symptoms in individuals with first episode bipolar disorder and schizoaffective disorder.

Many people with depression do not get better with standard treatments like medications or talk therapy. Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation treatment that uses magnetic pulses to stimulate areas of the brain involved in depression. One form of TMS called intermittent theta burst stimulation (iTBS) is FDA-cleared for depression and takes only 3 minutes to deliver. However, about one-third of patients do not respond to iTBS, and another one-third do not reach full remission. Improving iTBS requires a better understanding of how it works in the brain. iTBS is thought to work by strengthening connections between brain cells, a process called synaptic plasticity. This process depends on a type of brain receptor called the NMDA receptor. Most of what researchers know about how iTBS affects these connections comes from studies of healthy people. It is not known whether iTBS works the same way in the prefrontal cortex - the brain region targeted during depression treatment - or in people who actually have depression. This study has two phases. In Phase 1, both healthy volunteers and people with depression will complete 4 research visits to test how iTBS changes brain activity in the prefrontal cortex and whether medications that increase or decrease NMDA receptor activity change those effects. Each visit involves active or sham (inactive) iTBS combined with one of three study medications: a placebo (inactive pill), d-cycloserine (a medication that increases NMDA receptor activity), or dextromethorphan (a medication that decreases NMDA receptor activity). Brain activity is measured before and after each TMS session using electroencephalography (EEG), a painless test that records electrical signals from the scalp through a cap placed on the head. All participants also complete a brain MRI before beginning study visits for targeting purposes. In Phase 2, participants with depression will be offered a standard clinical course of 30 daily iTBS sessions (Monday through Friday over 6 weeks). Each session is combined with one blinded study medication (placebo, d-cycloserine, or dextromethorphan) taken daily. Brain activity measurements and standard depression and anxiety questionnaires are collected weekly throughout this phase to track how the brain changes over the course of treatment and whether those changes relate to improvements in symptoms. Together, the two phases of this study aim to identify the brain mechanism by which iTBS works in people with depression. This knowledge could lead to more effective TMS treatments for people who have not responded to medications or other therapies.

Posttraumatic stress disorder, or PTSD, can affect emotional health, sleep, daily functioning, and quality of life. Written Exposure Therapy is a brief trauma-focused psychotherapy in which participants complete structured writing exercises about a traumatic experience. However, it is not yet clear which changes in brain activity and sleep occur over the course of treatment or whether these measures can help predict who is most likely to benefit. This study will enroll approximately 200 adults with PTSD. Participants will be randomly assigned to either Written Exposure Therapy or a neutral writing condition and will complete five weekly writing sessions. The study will collect electroencephalography, or EEG, recordings and actigraphy-based sleep and activity measures at scheduled time points before treatment, during the five-week intervention period, and after treatment. Participants will also complete clinical assessments of PTSD symptoms and related outcomes. The primary goals are to identify EEG and sleep-related biomarkers associated with improvement in PTSD symptoms, determine how early these biomarkers change during treatment, and evaluate whether baseline measures can help predict individual treatment response.

The goal of this clinical trial is to learn whether two forms of one-day accelerated transcranial magnetic stimulation (TMS) can reduce depressive symptoms in adults with treatment-resistant depression. Treatment-resistant depression is depression that has not improved enough after at least two adequate antidepressant medication treatments. TMS is a non-invasive treatment that uses magnetic pulses to stimulate specific areas of the brain. The main questions this study aims to answer are: * Does continuous theta-burst stimulation (cTBS) targeting the precuneus reduce depressive symptoms 4 weeks after treatment compared with sham stimulation? * Does intermittent theta-burst stimulation (iTBS) targeting the left dorsolateral prefrontal cortex reduce depressive symptoms 4 weeks after treatment compared with sham stimulation? Researchers will compare precuneus cTBS, left dorsolateral prefrontal cortex iTBS, and sham stimulation to determine whether either active treatment reduces depressive symptoms more than sham stimulation. Participants will be randomly assigned to one of the three groups and will not be told which treatment they initially receive. Participants will: * Complete screening procedures and baseline assessments of depression, rumination, and cognitive function * Receive 20 sessions of active or sham TMS during one in-person study day * Complete follow-up assessments 1, 2, 3, and 4 weeks after the intervention * Report any side effects or medical problems experienced during the study Participants initially assigned to sham stimulation may choose to receive active TMS after completing the 4-week follow-up period. Those who choose this option will receive either precuneus cTBS or left dorsolateral prefrontal cortex iTBS and will complete additional follow-up assessments.

This study tests a new treatment for people with borderline personality disorder (BPD). The treatment combines a medication called D-cycloserine with one day of transcranial magnetic stimulation (TMS). The main questions it aims to answer are: * How many participants complete the treatment? * How do participants feel about the treatment? * Does the treatment have neurophysiological changes on participants? * Does the treatment improve BPD symptoms? * Do the benefits last over time? Participants will be asked to: * Come to the clinic for interviews and testing * Complete weekly questionnaires for 4 weeks before the treatment day * Take D-cycloserine the night before treatment * Attend one treatment day at the clinic. On that day, they may receive up to 20 short TMS sessions (each lasting 3 minutes and separated by 30 minutes). This visit may last up to 12 hours. * Complete weekly questionnaires for 6 weeks after the treatment day.

Despite their impact, postpartum intrusive thoughts- unwanted, distressing thoughts, images, and urges often about harming one's infant, are common yet overlooked. This can lead to distress, shame, impairment, and for some, diagnoses of depression, anxiety, or OCD. This project aims to adapt and test a brief, accessible intervention targeting misinterpretation of postpartum intrusive thoughts.

Despite the proliferation of cannabis and cannabinoid products in recent years, little research has been done to determine the impact of these products on womens health conditions, including endometriosis. This study is designed to assess the impact of a custom-formulated, hemp-derived, full-spectrum, high-CBD product vs. placebo on clinical symptoms and biomarkers over the course of 12 weeks of treatment in patients with endometriosis. This project will provide information that does not currently exist on the potential efficacy of a cannabinoid-based sublingual product for endometriosis.

Exposure therapy is the most effective treatment available for obsessive compulsive disorder, yet up to 50% of patients do not recover because the mechanisms underlying successful response are poorly understood, leading to significant variability in how clinicians conduct exposure therapy. The main purpose of this study is to determine which target mechanisms are most critical to engage in real-world exposure sessions to produce good treatment outcomes. Adult participants (N = 400) with Obsessive Compulsive Disorder (OCD) receiving exposure therapy from two sites (McLean Hospital, San Diego State University) across the continuum of care (outpatient, partial hospital, residential) will complete baseline clinical and demographic measures as well as weekly symptom reports. The project will measure exposure mechanisms across three levels of analysis (self-report, observer-rated behavior, physiology) during each exposure session. Mechanisms assessed will include a broad range of variables based on both habituation and inhibitory learning models of exposure. Self-report and observer-rated mechanisms will be measured with the Exposure Feedback Form, created and piloted by the study team. Physiological mechanisms will include skin conductance response, heart rate, and heart rate variability measured with a wristwatch. The current study will determine (1) which exposure mechanisms lead to favorable clinical outcomes, and (2) what makes a good exposure for whom. Results of this study have the potential to improve personalized care for the many patients who do not remit following exposure therapy for OCD.

The aim of this trial is to evaluate the feasibility and preliminary efficacy of using passive smartphone sensors to detect moments of heightened negative mood and inform the timing of brief mental health interventions, such as mindfulness exercises and psychoeducation, in adults with early psychosis.

This is a randomized, double-blind, placebo-controlled proof-of-concept clinical trial to assess the efficacy and safety of Magnesium-vitamin B6in combination with treatment as usual for treating symptoms of depression, stress, and anxiety in patients with first episode bipolar I disorder.

A growing body of research implicates rumination as being a transdiagnostic risk factor involved in the development of depression and anxiety in youth. Critically, mindfulness meditation has shown significant promise in targeting rumination, and ultimately improving depressive and anxiety symptoms. Mindfulness apps offer a convenient and cost-effective means for accessing mindfulness training, while being interactive and engaging for youth. Despite their growing popularity among teens, strikingly little research has been conducted on these apps. Two critical questions have yet to be addressed: (1) what are the underlying neural and cognitive mechanisms that account for the beneficial effects of these apps and (2) for whom is app-based mindfulness well-suited. To address these gaps, adolescents (ages 13-18) will be randomly assigned to an app-delivered mindfulness course vs. a control condition and will complete pre- and post-intervention resting state functional magnetic resonance imaging (fMRI) scans to probe static and dynamic functional connectivity within - and between - brain networks strongly implicated in mindfulness training and rumination. In addition, cognitive tasks will be administered at pre- and post-intervention to assess attentional control abilities putatively enhanced by mindfulness training. Finally, mindfulness skills and changes in rumination will be assessed via smartphone-based ecological momentary assessment (EMA). First, the investigators will test whether changes in (1) brain functional connectivity, (2) attentional control and (3) acquisition and use of mindfulness skills mediate between-group (i.e., app vs. control) differences in the reduction of rumination. Second, the investigators will test whether a machine learning model incorporating baseline clinical, demographic, and psychosocial characteristics can be used to identify which adolescents are predicted to benefit from app-based mindfulness training.

Lack of perceived control, particularly during stress, has been critically implicated in major depressive disorder (MDD) and anhedonic symptoms, especially among female adolescents; yet the neural underpinnings of perceived control disruptions in MDD remain poorly understood. Using functional magnetic resonance imaging with a novel "value of control task" in conjunction with a prospective design, this study will provide a comprehensive understanding of stress and perceived control related mechanisms in female adolescents with MDD and will examine stress-induced disruptions in perceived control as a predictor of "real world" expressions of maladaptive coping and anhedonia.

The study will investigate whether a nociceptin receptor antagonist will normalize neural and behavioral processes of approach/avoidance decision-making in unmedicated individuals with major depressive disorder (MDD) and anxiety disorders. More specifically, the study aims to investigate dysregulation within (1) corticostriatal-midbrain circuitry and (2) nociceptin/orphanin FQ peptide and the nociceptin receptor (NOPR).

This study will conduct a randomized controlled trial of Cognitive Bias Modification for Interpretation (CBM-I) as an augmentation to treatment as usual for obsessive compulsive disorder (OCD). CBM-I is a digital intervention designed to directly manipulate interpretation bias through repeated practice on a training task, thereby inducing cognitive changes in a relatively automatic or implicit manner. Specifically, this study will examine the feasibility, acceptability, and clinical outcomes associated with CBM-I. Adults with obsessive compulsive disorder (OCD) will be recruited from a treatment program for this disorder and participants will be randomly assigned to either receive: 1) up to 12 sessions of CBM-I, or or up to 12 sessions of psychoeducation as a control condition.

The goal of this study is to test whether combining D-serine with 30 treatments of a) iTBS and b) 18-Hz protocols will enhance clinical outcomes compared to rTMS with placebo (i.e., sugar pill). The investigators hypothesize that NMDA receptor activation via D-serine combined with repeated sessions of rTMS will produce greater clinical outcomes than iTBS with placebo and 18-Hz with placebo.

Many people with depression do not get better with standard treatments like medication. One promising alternative is transcranial magnetic stimulation (TMS), a non-invasive procedure that uses magnetic pulses to stimulate specific brain regions. A particular pattern of TMS called continuous theta-burst stimulation (cTBS) is thought to reduce overactive brain activity in depression, but the investigators do not yet fully understand how it works at the level of brain cells and connections. This study aims to determine the biological mechanism by which cTBS changes brain activity in people with depression. Specifically, the investigators are testing two competing ideas: (1) that cTBS works by weakening the connections between brain cells through a process called long-term depression (LTD), which is driven by a chemical messenger system called glutamate; or (2) that cTBS works by increasing the brain's natural "braking" system, driven by a different chemical messenger called GABA. To test these ideas, participants with depression will receive cTBS along with one of four FDA-approved medications, or placebo, that either boost or block these chemical messenger systems. The investigators will measure changes in brain activity using electroencephalography (EEG) recorded simultaneously with TMS. Specific patterns in the EEG signal, called TMS-evoked potentials (TEPs), act as a window into how different brain cell types are responding to stimulation. Each participant will complete four study visits, each testing a different drug-TMS combination in random order. One group of participants will test drugs targeting the glutamate system (d-cycloserine and memantine). A second group will test drugs targeting the GABA system (lorazepam and baclofen). All drugs are given as a single oral dose and are commonly used in clinical practice. Understanding exactly how cTBS works at a biological level could open the door to more effective, personalized TMS treatments.

The goal of this clinical trial is to learn if a 1-on-1 support program is easy to complete and acceptable for people supporting loved ones who have recently received treatment for substance use. The main questions it aims to answer are: How many people complete the program? How satisfied are people with the program? Participants will: Complete weekly telehealth sessions for 12 weeks Complete surveys/interviews at the beginning, in the middle (\~week 6), at the end of the program (\~week 12), and 12-weeks after the end of the program Complete a focus group or interview

The goal of this study is to develop a new tool for measuring substance use disorder treatment outcome. We will start by interviewing people and gathering advisory groups to develop the items for this new tool.

Preliminary data have suggested that cannabidiol (CBD) may have a number of clinical benefits, including anti-anxiety and antidepressant properties. This study is a pilot open-label clinical trial assessing a custom-formulated high-CBD product over the course of 4 weeks in patients with bipolar disorder who experience anxiety.

The goal of this clinical trial is to compare engagement in treatment in coordinated specialty care (CSC) to five extra care elements (CSC 2.0) in first-episode psychosis. The main question it aims to answer is: • Does the addition of certain elements of care increase the number of visits in treatment for first-episode psychosis? Participants will either: * Receive care as usual (CSC) or * Receive care as usual (CSC) plus five additional care elements (CSC 2.0): 1. Individual peer support 2. Digital outreach 3. Care coordination 4. Multi-family group therapy 5. Cognitive remediation Researchers will compare the standard of care (CSC) to CSC 2.0 to see if participants receiving CSC 2.0 have more visits to their clinic in their first year.

The goal of this clinical trial is to learn how Written Exposure Therapy (WET), a brief treatment for PTSD, works among individuals with substance use disorders (SUD) engaged in residential SUD treatment and how biology may influence treatment. The main questions it aims to answer are: * Does WET improve PTSD and substance use outcomes among individuals with SUD+PTSD? * Does WET improve physiological responses and craving to trauma cues? * Do sex hormones influence changes physiological responses and craving during treatment among women? Participants will: * Complete WET or a neutral writing in addition to their residential SUD treatment * Complete two laboratory sessions before and after treatment * Complete follow-up surveys and interviews at 1- and 3-months post-treatment

This study uses a noninvasive technique called transcranial magnetic stimulation (TMS) to study how hallucinations work in schizophrenia. TMS is a noninvasive way of stimulating the brain, using a magnetic field to change activity in the brain. The magnetic field is produced by a coil that is held next to the scalp. In this study the investigators will be stimulating the brain to learn more about how TMS might improve these symptoms of schizophrenia.

Severe childhood adversity accounts for a large portion of psychiatric illness, and an increased risk for major depressive disorder (MDD). For some individuals, childhood adversity has negative psychological and medical consequences; others preserve mental and physical health despite such experiences (they are resilient). In spite of this, little is known about the neurobiological mechanisms related to childhood adversity, especially oxidative stress abnormalities in the brain. To fill this gap, this study combines functional, structural, and molecular imaging approaches to examine the role of oxidative stress abnormalities related to childhood adversity.

This project's main goal is to use state-of-the-art passive sensing techniques to identify digital biomarkers that relate to bioenergetic changes in the brain due to nicotinamide riboside supplementation in those with mild cognitive impairment and mild Alzheimer's dementia.