Clinical Research Directory

NEURO-COGS: Neurometabolic Mechanisms of Cognitive Training in Schizophrenia

This study will examine brain metabolic and excitatory/inhibitory mechanisms related to cognitive and visual functioning in adults with schizophrenia and healthy control participants. Participants will complete behavioral assessments, cognitive testing, electroencephalography, magnetic resonance imaging, and magnetic resonance spectroscopy assessments. After baseline assessments, participants will be randomly assigned to one of two computerized cognitive training programs: perceptual discrimination training or cognitive control training. Each training program will include approximately 10 hours of training over 2 to 6 weeks. The study will evaluate changes in cognitive and visual task performance, EEG measures, and brain metabolite concentrations before and after cognitive training. Some participants may also complete optional extended baseline assessments before cognitive training.

Effectiveness of Motivation Skills Training (MST)

This study will take place at four outpatient clinics serving adults with serious mental illness. Informed consent will be obtained from N=80 individuals with a Diagnostic and Statistical Manual of Mental Illnesses (DSM)-5 diagnosis of schizophrenia or schizoaffective disorder meeting inclusion/exclusion criteria to participate in a randomized controlled trial comparing Motivation Skills Training (MST) to a Healthy Behaviors Control (HBC) group. Eligible participants will receive a baseline assessment including sociodemographic and psychosocial assessments, measures of motivation, goal attainment, and quality of life, as well as measures of executive skills, community functioning, and psychiatric symptoms severity. Both MST and HBC will be implemented as once weekly group therapies. The treatment phase is approximately 12-14 weeks. MST will focus on motivation knowledge and self-regulation skills while HBC will focus on physical health and health-related skills.

Magnetic Seizure Therapy for Schizophrenia - Trial

This trial aims to assess the clinical effects and tolerability of Magnetic Seizure Therapy (MST) as an alternative to electroconvulsive therapy (ECT) for Treatment Resistant Schizophrenia (RS).

Theta-Burst Transcranial Magnetic Stimulation for Treatment-Resistant Auditory Hallucinations

The goal of this clinical trial is to learn whether theta-burst transcranial magnetic stimulation (TBS), a non-invasive brain stimulation technique, can help reduce persistent auditory verbal hallucinations (hearing voices) in adults with psychotic disorders who have not responded adequately to antipsychotic medications. The main questions it aims to answer are: * Does theta-burst stimulation reduce the severity of auditory verbal hallucinations? * Does theta-burst stimulation improve other psychiatric symptoms, including depressive symptoms and insight into illness? * How well do participants tolerate this treatment, and what side effects do they experience? All participants will receive active theta-burst stimulation. There is no placebo or comparison group. Participants will: * Complete an initial assessment of their mental health, symptoms, and medical history. * Receive 20 brain stimulation sessions over two consecutive weeks, with two sessions per day on weekdays. * Complete follow-up assessments approximately one week and one month after treatment to evaluate changes in symptoms and overall functioning. * Report any side effects experienced during treatment and follow-up.

Functional Relevance of Dopamine Receptors in Healthy Controls and Patients With Schizophrenia: Characterization Through [11C]NNC-112 and [18F]Fallypride Positron Emission Tomography

Background: * Some illnesses, such as schizophrenia, have effects on brain cells called dopamine receptors, which are required for normal brain function. People with schizophrenia have difficulty thinking and experience hallucinations and delusions. Medications that change brain dopamine receptors can decrease these hallucinations and delusions. * The cause of schizophrenia and its association with brain dopamine receptors is not known but may be clarified by studying dopamine receptors in people who have dopamine disorders (such as schizophrenia) and those who do not. Researchers are interested in studying the dopamine system to gain a better idea of how dopamine disorders develop, which may lead to better medical care for people with schizophrenia. Objectives: \- To study the amount and distribution of two types of dopamine receptors. Eligibility: * Individuals between the ages of 18 and 60 who have schizophrenia. * Healthy volunteers between the ages of 18 and 90. Design: * Participants will undergo a full screening, with physical and psychological history, a neurological examination, and blood and urine samples. * Participants will have a blood flow map of the brain recorded with a positron emission tomography (PET) brain scan. A magnetic resonance imaging (MRI) scan will also be performed to determine brain anatomy. * To study the amount and distribution of dopamine receptors in the brain, participants will receive a small amount of a radioactive chemical in the vein, followed by a PET scan. * The procedure will be performed twice in two separate sessions, once for \[18F\]fallypride and once for \[11C\]NNC-112.

Integrated Psychoeducation Program for Internalized Stigma in Schizophrenia

The goal of this pilot randomized controlled trial is to investigate whether the Integrated Psychoeducation Program reduces internalized stigma and improves related outcomes in adults with schizophrenia or schizoaffective disorder, and whether the program is feasible to deliver in a community mental health setting. The main question it aims to answer is: Do participants who receive the program show a greater reduction in internalized stigma from pre-test to post-test than participants in a waitlist control group who continue treatment as usual? Researchers will also examine changes in self-esteem, hopelessness, and psychological flourishing, whether changes are maintained at 3-month follow-up, and attendance and retention rates. Participants in the intervention group will attend 8 weekly group sessions that combine psychoeducation, an expressive writing exercise, and breathing/relaxation exercises. Participants in the waitlist control group will continue treatment as usual and will be offered the program after the study. All participants will complete questionnaires before the program (pre-tests), after the program (post-tests), and 3 months after the post-tests (3-month follow-up).

Incentives and Long-Acting Injectable Adherence After Involuntary Hospitalization

This study is a randomized controlled trial evaluating the impact of financial incentives on medication adherence among individuals with schizophrenia, schizoaffective disorder, or bipolar disorder and/or co-occurring substance use disorder who are recently discharged from involuntary hospitalization or are at high risk of future involuntary hospitalization. Participants will be randomized to receive financial incentives for adherence to long-acting injectable medications or to a control group.

Comparing Two Behavioral Approaches to Quitting Smoking in Mental Health Settings

The study team will conduct a Multisite Randomized Controlled Trial to evaluate the advantages and disadvantages of two approaches for quitting smoking among people with serious mental illness (SMI). The study will compare a novel app tailored to people with SMI, Quit on the Go, to a standard of care smoking cessation intervention. We will test the effectiveness of the Quit on the Go app, an intervention that has demonstrated feasibility and acceptability in the target population, as a tool for smoking cessation in people with SMI. Participants with SMI will be recruited across 3 sites (Duke University, Univ. at Buffalo, and Wake Forest University).

A Mobile App to Support Mood, Daily Routines and Medication Adherence in Adults With Severe Mental Illness

The goal of this clinical trial is to learn whether MoodSync, a mobile application for patients and their family caregivers, improves mood stability, medication adherence, daily functioning and early detection of relapse warning signs in adults with severe mental illness in Bahrain. The main question it aims to answer is: Does MoodSync plus standard care improve manic symptoms, medication adherence, practical and social functioning, and early warning signs more than standard care alone? Participants will be randomly assigned to MoodSync plus standard care or standard care alone. MoodSync participants will use the patient app for 12 weeks for daily mood check-ins, sleep and activity tracking with a wearable device, medication reminders, daily-routine (social rhythm) support and early warning-sign reporting. A nominated family caregiver may use the linked caregiver app. All participants continue standard care and complete questionnaires before and after the intervention period. Research hypothesis: \* Patients who use MoodSync will show greater improvement in mood symptoms, medication adherence, practical and social functioning, and relapse-related outcomes than patients receiving standard care alone.

Assessment of Acute Psychomotor Agitation Measures Associated With Schizophrenia and Bipolar Disorder

This open-label study will utilize treatment with BXCL501 in order to assess the suitability of patient-and lay informant-assessed outcome measures for evaluation of severity of psychomotor agitation episodes in patients with Bipolar Disorders, Schizophrenia, Schizoaffective, and Schizophreniform disorders and correlate them with clinician-assessed ratings.

Genetic Study of Schizophrenia

This large ongoing study at NIMH investigates the neurobiology of schizophrenia by identifying susceptibility genes, evaluating their impact on brain function to better understand how to treat and prevent this illness.

Cognitive Neurocomputational Task Reliability & Clinical Applications Consortium (CNTRACS): Study 1

In Study 1, investigators will test the ability of each of the seven paradigms to differentiate between schizophrenia (SZ)/schizoaffective disorder (SZA) and matched healthy control subjects (HC) and to predict individual differences in clinical measures of hallucinations and delusions (as well as measures of function). Investigators will also directly compare the tasks in terms of predictive ability and psychometric properties and determine whether the tasks share variance or explain unique variance. This will include determining whether hallucinations and delusions are best explained by separate underlying processes or by a single process. Investigators will also test whether the model-based parameters from these studies are more precise and sensitive than standard behavioral methods for assessing deficits across psychotic disorders and for predicting hallucinations and delusions (Aim 1). Investigators will also validate key model-based parameters against well-characterized neurophysiological measures using electroencephalogram (EEG) (Aim 4). The data from Study 1 will also be used to optimize (e.g., length, floor, and ceiling effects) tasks for Study 2. To generate a sample with sufficient variation in hallucinations and delusions, investigators will recruit the following groups that balance feasibility with clinical relevance: A) healthy controls (HC) \[HC, N=125\]; B) schizophrenia and schizoaffective disorder \[SZ/SZA, N=200\]). For Study 1, investigators will ensure that 40 patients are unmedicated. Investigators anticipate a \~20% screen fail/drop-out rate based on our prior Cognitive Neuroscience Test Reliability and Clinical Applications for Schizophrenia Consortium (CNTRACS) studies. Thus, investigators will run an additional 40 SZ/SZA and 15 HC. All sites have experience recruiting patients in each of these groups as indicated by our past successful studies, and the fact that investigators have been able to recruit patients with significant hallucinations and delusions in all groups. Investigators will also validate key model-based parameters against well-characterized neurophysiological measures using electroencephalogram (EEG) (Aim 4). The data from Study 1 will also be used to optimize (e.g., length, floor, and ceiling effects) tasks for Study 2. To generate a sample with sufficient variation in hallucinations and delusions, investigators will recruit the following groups that balance feasibility with clinical relevance: A) healthy controls (HC) \[HC, N=125\]; B) schizophrenia and schizoaffective disorder \[SZ/SZA, N=200\]). For Study 1, investigators will ensure that 40 patients are unmedicated. Investigators anticipate a \~20% screen fail/drop-out rate based on our prior Cognitive Neuroscience Test Reliability and Clinical Applications for Schizophrenia Consortium (CNTRACS) studies. Thus, investigators will run an additional 40 SZ/SZA and 15 HC. All sites have experience recruiting patients in each of these groups as indicated by our past successful studies, and the fact that investigators have been able to recruit patients with significant hallucinations and delusions in all groups.

State Representation in Early Psychosis 2

This observational study will examine behavioral and electroencephalography measures related to state representation in individuals with early psychosis and healthy control participants. Participants will complete clinical interviews, self-report measures, cognitive assessments, computerized behavioral tasks, and EEG assessments. The study will evaluate performance and computed parameters from the Translational Orientation Pattern Expectancy task and Translational Bandit Task, along with EEG variables related to cognitive control, reward processing, and neural synchrony. The study aims to better understand heterogeneity in early psychosis and identify neurocognitive and neurophysiologic markers that may inform future precision psychiatry approaches.

A Study to Evaluate the Effectiveness of Valbenazine in Adult Participants With Tardive Dyskinesia (TD) Who Remain Symptomatic While Receiving or After Stopping a Vesicular Monoamine Transporter 2 (VMAT2) Inhibitor

This study will evaluate the efficacy of valbenazine on clinician- and patient-reported outcomes in participants with TD while receiving or after stopping a VMAT2 inhibitor.

LRFN5 and OLFM4 in Schizoaffective Disorder

Schizoaffective disorder (SAD) is a chronic psychiatric condition characterized by psychotic and mood symptoms. Emerging evidence suggests that Leucine-Rich Repeat and Fibronectin Type-III Domain-Containing Protein 5 (LRFN5) and olfactomedin-4 (OLFM4) may play roles in synaptic organization, neurodevelopment, and neuroinflammation. However, no prior study has investigated these biomarkers in SAD. This cross-sectional case-control study aims to compare peripheral serum levels of LRFN5 and OLFM4 in subjects diagnosed with SAD in remission and healthy control subjects. The study also assessed associations between these biomarkers and clinical symptom severity, global functioning, and systemic inflammation measured by the Aggregate Index of Systemic Inflammation (AISI). The study aimed to investigate convergent synaptic and immunoinflammatory dysregulation in SAD.

Cognitive Behavioral Social Skills Training in Early Onset Psychosis

Cognitive-behavioral therapy (CBT) and social skills training (SST) are recommended psychological interventions to improve symptomatology and functional recovery in psychosis. In addition, CBT may reduce hyperactivation of the brain structures responsible for the stress response. In patients with early onset psychotic disorder (EOP) there are not any previous controlled study that has analyzed the efficacy of this type of intervention. The aim of this study is to investigate efficacy of CBT + SST in symptomatic and functional improvement after the treatment in patients with EOP. The study will also examine the potential effect of the intervention on neurobiological stress markers.

Switching From Twice-Daily to Once-Daily Clozapine Dosing in Schizophrenia

Plasma half-life has routinely been used to establish the dosing schedule of antipsychotics; for example, it is recommended that agents with a short plasma half-life be administered multiple times per day. However, to date, several randomized controlled trials (RCTs) have shown no differences in clinical outcomes between once- and twice-daily dosing of various antipsychotics, suggesting that once-daily dosing of antipsychotics is a viable option regardless of plasma half-life. This would apply to clozapine as well; however, there have been no studies comparing once-daily vs. twice-daily dosing regimens of clozapine in terms of efficacy and tolerability. To address this gap in the literature, the investigators shall conduct a pilot, double-blind, RCT to examine efficacy and tolerability following a switch to once-daily dosing regimen of clozapine in patients with schizophrenia receiving clozapine twice a day.

Impact of Medication Education on Adherence and Side Effects

Severe mental disorders such as schizophrenia, bipolar disorder, and psychotic depression often require long-term or lifelong medication treatment. However, many psychiatric patients have difficulty adhering to their prescribed medication regimens due to factors such as lack of information, fear of side effects, and negative experiences with psychotropic medications. Poor treatment adherence is associated with symptom relapse, prolonged hospitalization, increased rehospitalization rates, reduced quality of life, and higher health care costs. Medication education is a key psychosocial intervention aimed at improving patients' understanding of their illness, treatment process, and potential medication side effects. Providing structured medication education may enhance treatment adherence and help patients recognize and manage side effects more effectively. This intervention study aims to evaluate the effect of a structured medication education program on treatment adherence and medication-related side effects among psychotic inpatients hospitalized in a psychiatric clinic, including patients diagnosed with schizophrenia, schizoaffective disorder, schizophreniform disorder, bipolar disorder with psychotic features, and major depressive disorder with psychotic features. The findings of this study are expected to contribute to the development of effective psychosocial interventions to improve medication adherence and treatment outcomes in psychiatric inpatient settings.

Cerebellar Modulation of Cognition in Psychosis

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.

The OPUS YOUNG Trial. Early Intervention Versus Treatment as Usual for Adolescents With First-episode Psychosis

The OPUS YOUNG (OY) study investigates the efficacy of early intervention service versus treatment as usual (TAU) for adolescents aged 12-17 years with a first-episode psychosis. In Denmark, the yearly incidence of schizophrenia in youth below the age of 18 years has increased from 137 in 2000 to 477 in 2016. Outcomes in people with schizophrenia spectrum disorders are suboptimal with low quality of life, low rates of recovery, substance misuse, higher rates of suicide, violence and legal problems, low educational and vocational attainment, and a significantly reduced life-expectancy of 15-20 year. Schizophrenia imply a large burden of disease with severe impact on patients, their families, the service system and a large economic societal burden. The investigators will include 290 participants age 12-17 years with an early onset psychosis within the following diagnostic classes: schizophrenia spectrum, psychotic depression or drug-induced psychosis. The design is an independent, investigator initiated, pragmatic, randomized clinical trial, with blinded outcome assessment. Participants are randomized 1:1 to OY or TAU. Participants in OY are offered 2 years of specialized intervention (OY) regardless of age, while participants in TAU are switched to adult psychiatry at the age of 18 years. OY builds on the Danish evidenced based intervention for young adults, OPUS, adjusted to meet the specific needs of adolescents: intensified support for caretakers and relatives including siblings; social cognition and interaction treatment; and individual cognitive behavioral case management. OY addresses the specific challenges of psychopharmacologic treatment in youth; supported transition to adult care after OY; school or educational support; and prevention and treatment of substance misuse. The primary endpoint is improved functioning in daily and social life after 24 months. Secondary outcome measures are psychopathology, quality of life, family stress, and retention in treatment and school/employment, and healthcare consumption. The clinical and societal perspective of a large scale implementation is improved prevention of the negative consequences of early-onset psychosis and a reduced burden of severe mental illness.

Enhancing Veteran-Clinical Collaboration in VA PRRCs

Over 60% of Veterans with serious mental illness have a service-connected disability that impairs their ability to work, go to school, and/or have successful personal lives. Although traditional treatments tend to focus on symptom remission, Veterans prioritize a range of treatment goals, including personal empowerment and gaining personally meaningful skills. Increasing Veteran-clinician collaboration can help effectively align care with each Veteran's goals and support an empowering therapeutic experience. This project will evaluate the effectiveness of a group-based intervention intended to increase Veterans' comfort, confidence, knowledge, and skills to collaborate with their treatment teams. Findings from this study will contribute important knowledge about this intervention's effectiveness and how to enhance its effectiveness, especially for Veterans from minoritized groups. If the decision-making intervention is effective, it would help Veterans with serious mental illness, and might also help Veterans with other chronic health conditions, like PTSD and chronic pain.

Ketogenic and Nutritional Interventions for First Episode Bipolar Disorder

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.

Open Label Extension Study of NCT06221852

This is a 12-week open-label extension study for participants completing study NCT06221852.

Dexmedetomidine in the Treatment of Agitation Associated With Schizophrenia

This is a definitive study to support the safety and efficacy evaluation of BXCL501 for the acute treatment of agitation in schizophrenia. The BXCL501-301 study is designed to characterize the efficacy, safety and tolerability of BXCL501 (sublingual film formulation of DEX, HCl) in agitation associated with schizophrenia, schizoaffective disorder or schizophreniform disorder.