Clinical Research Directory

A Study to Evaluate the Efficacy and Safety of KarXT for the Treatment of Schizophrenia in Adolescents (EMERGENT TEEN)

The purpose of this study is to evaluate the efficacy and safety of KarXT for treatment of Schizophrenia in adolescents.

tACS for Working Memory in Schizophrenia

This study is a randomized, single-blind, sham-controlled crossover trial enrolling 30 schizophrenia patients, each receiving one active and one sham tACS session (7-day washout), targeting P3/P4 at individual alpha frequency (2mA, 30min) during a working memory task, with accuracy and reaction time as primary outcomes, alongside EEG and neurophysiological measures, to test the efficacy and mechanisms of individualized alpha-tACS on working memory.

Studies of Frontal Lobe Brain Functioning in Schizophrenia

The purpose of this study is to use brain imaging technology to investigate the role of the frontal lobe of the brain in the thinking of individuals with schizophrenia and other neuropsychiatric disorders and healthy volunteers. Participants in this study will undergo a positron emission tomography (PET) scan of the brain while performing neuropsychological tests. Some of the tests involve cognitive operations that depend upon the frontal cortex. Interactions between frontal lobe activation, cognitive behavior, and neuropharmacology will be assessed by measuring regional cerebral blood flow (rCBF) during treatment with drugs that may affect frontal lobe physiology.

Eye-Movement Intervention for Cognitive Impairment Across Schizophrenia Spectrum

The goal of this clinical trial is to determine whether a gamified eye-movement intervention can improve cognitive function in individuals across the schizophrenia spectrum, including clinical high-risk individuals, first-episode schizophrenia patients, and chronic schizophrenia patients. The main questions it aims to answer are: * Does eye-movement training improve cognitive performance measured by the MATRICS Consensus Cognitive Battery (MCCB)? * Does eye-movement training improve oculomotor functions and clinical symptoms across different illness stages? Researchers will compare an eye-movement intervention group with an active control group receiving matched finger-controlled game training to determine whether the eye-movement intervention produces greater improvements in cognitive function and eye-movement performance. Participants will: * Receive either gamified eye-movement training or matched finger-controlled game training for 4 weeks. * Complete cognitive assessments using the MCCB before and after the intervention. * Complete standardized eye-tracking tasks, including fixation stability, smooth pursuit, antisaccade, and free-viewing tasks, to evaluate changes in oculomotor control and visual exploration patterns. * Complete clinical symptom assessments using SOPS or PANSS according to illness stage.

The Effect of Comorbid Alcohol/Substance Use

Study Design This study was designed as a comparative, cross-sectional case-control study examining the effect of comorbid alcohol and substance use disorder (ASUD) on clinical course and social inclusion among individuals with severe mental illness followed at a Community Mental Health Center (CMHC). The study did not involve any interventions. Aim The aim of this study is to examine the effect of comorbid alcohol and substance use on clinical course parameters-such as number of hospitalizations and medication dosages-and on social inclusion indicators-such as employment, social participation, and social adjustment-among individuals with severe mental illness followed at the CMHC, in comparison with a matched control group without substance use. Research Questions What are the rates of comorbid alcohol and substance use among patients with severe mental illness followed at the CMHC? What are the current addiction symptoms, number of hospitalizations, and employment rates among individuals with severe mental illness and comorbid ASUD? What is the level of continuity of CMHC engagement and social participation among individuals with severe mental illness and comorbid ASUD, and what factors influence it? How does the level of social inclusion among individuals with severe mental illness and comorbid ASUD compare with that of individuals without ASUD? Hypotheses H1: The average annual number of hospitalizations among individuals with a dual diagnosis (severe mental illness + ASUD) followed at the CMHC is significantly higher than among those without substance use. H2: Among individuals with a dual diagnosis, the daily medication doses (e.g., chlorpromazine equivalents) required to control psychotic or manic symptoms are higher than in the control group. H3: Social inclusion is lower among patients with substance use compared with the control group. H4: Employment rates among individuals with a dual diagnosis are significantly lower than among those with severe mental illness alone. H5: Substance use negatively affects patients' social participation, including involvement in activities and friendships. H6: Attendance rates at CMHC workshops and rehabilitation programs are lower among individuals with substance use compared with the control group.

EPI-MINN: Targeting Cognition and Motivation - National

The purpose of this study is to perform a practice-based research project designed to assess whether cognition and motivated behavior in early psychosis can be addressed as key treatment goals within real-world settings by using a 12-week mobile intervention program. We will recruit participants who are receiving care for early psychosis from clinics across the United States. We will compare outcomes from participants who receive treatment at coordinated specialty care (CSC) early psychosis clinics to those that receive standard community care. A qualifying CSC program will provide comprehensive clinical services such as psychotherapy, medication management, psychoeducation, and work or education support. This study will be conducted remotely, and participants can participate at home with their own electronic devices. The aim of this study is to investigate a well-defined 12-week mobile intervention program specifically designed to target cognitive functioning and motivated behavior for individuals with early psychosis. Participants will complete a screening interview which will include diagnosis and symptom ratings, neurocognitive assessment, and self-reports of symptoms, behavior, and functioning. Then participants will be randomized to receive the 12-week mobile intervention, or an active control of treatment as usual. The investigators will test for differences in the clinical trajectories after training, and at two follow up appointments at 6 and 12 months post-training.

Inpatient Evaluation of Adults With Schizophrenia

The purpose of this study is to understand the biologic basis of schizophrenia and to determine which symptoms are related to the illness itself and which are related to medications used to treat the illness. Schizophrenia and related psychoses are chronic brain disorders whose prognosis is often poor and whose pathophysiology remains obscure. Brain imaging technologies such s positron emission tomography (PET), functional magnetic resonance imaging (fMRI), and magnetic resonance imaging (MRI) offer opportunities to study the pathophysiology of psychotic disorders by evaluating brain function. However, the use of anti-psychotic drugs may interfere with the results of such studies. In this study, psychotropic medication will be discontinued in patients for a short period of time to distinguish the effects of the illness on the brain without the interference of the medication's effects on the brain. Given that there is a risk that the patient's symptoms will increase, they are asked to stay on an inpatient unit where the NIMH clinical staff is available to help them 24 hours a day. This study will be conducted in three phases. In Phase 1, participants will be admitted to the Clinical Center while continuing to take their medication and will undergo diagnostic interviews, physical and laboratory assessments, physiological monitoring, and neuropsychological testing. Behavioral ratings will also be performed and blood and urine samples will be collected. During Phase 2, participants will continue taking medications in a blinded fashion for 8 to 12 weeks. The active medications will be replaced with a placebo (an inactive pill) part of that time. PET, fMRI, and MRI scans will be used to monitor how the continuation or lack of medication affects the brain. Psychological tests will also be given to measure changes in cognition. In Phase 3, participants will have the opportunity for clinical stabilization....

Digital Implementation Support to Achieve Uptake and Integration of Task-Shared Care for Schizophrenia in Primary Care in India

Schizophrenia represents a significant contributor to the global burden of disease, with this burden disproportionately impacting low- and middle-income countries (LMICs). In India, the burden due to schizophrenia is further exacerbated by low access to effective psychosocial interventions aimed at promoting recovery, rehabilitation, and community tenure, as well as inadequate attention to managing co-occurring chronic medical conditions that result in significantly reduced life expectancy among those living with schizophrenia compared to the general population. A major driver of these alarming gaps in access to care for persons with schizophrenia in India is the limited capacity within primary care settings aimed at addressing the complex co-occurring mental health, physical health, and functional needs of this patient population. There now exists strong evidence demonstrating that community programs delivered in primary care and leveraging psychosocial interventions combined with linkage to specialty psychiatric services are effective for supporting treatment and recovery of schizophrenia in low-resource settings. We will leverage our existing collaboration and robust research infrastructure in both rural and urban settings in Madhya Pradesh and Karnataka, India to conduct a hybrid type 1 effectiveness-implementation trial to evaluate whether the use of a digital platform offers added clinical benefit and can support integration of this task shared care for schizophrenia into routine primary care settings. We will address the following aims: 1) evaluate whether the use of the mindLAMP digital platform can enhance the clinical effectiveness of task-shared community-based psychosocial rehabilitation (COPSI) for individuals with schizophrenia, and 2) determine whether the addition of mindLAMP to the delivery of the COPSI program has an impact on implementation metrics when compared to delivery of COPSI alone.

Anticholinergic Deprescription in Schizophrenia

In this study, the investigators will examine whether a deprescription of unnecessary anticholinergic drugs (benztropine or trihexyphenidyl) can augment quality of life, functioning, and neurocognition in individuals who with schizophrenia. Individuals identified by clinical services who have unneeded prescriptions benztropine or trihexyphenidyl will be eligible for deprescription and study entry. Following a baseline evaluation and magnetic resonance imaging (MRI), participants will will be randomized to either staying on their anticholinergic drugs or undergoing deprescription per routine clinical care, and will undergo follow-up evaluations across 6 months. The investigators predict that reducing and deprescribing these drug, if clinically determined to be unnecessary will will enhance functioning, neurocognition

A Study to Assess the Efficacy and Safety of ML-007C-MA for the Treatment of Inpatient Adults With Schizophrenia

ML-007C-MA-211 is a Phase 2, randomized, double-blind, placebo-controlled study to evaluate the efficacy, safety, and tolerability of orally administered ML-007C-MA in inpatient adult participants aged 18 to 64 years with schizophrenia experiencing an acute exacerbation of psychosis. The primary objective is to evaluate the efficacy of ML-007C-MA compared with placebo in the treatment of subjects with inadequately controlled symptoms of schizophrenia as measured by the Positive and Negative Syndrome Scale (PANSS) Total Score.

Proposal To Develop A Rapid And Cost-Effective Diagnostic Test For Schizophrenia

Schizophrenia is a severe psychotic illness of unknown cause that affects 1% of the population worldwide. Currently, there is no diagnostic test for schizophrenia. Instead, the diagnosis is typically established through a psychiatric interview of the patient, who is evaluated against a set of established criteria of signs and symptoms. It can take many months to years to establish a diagnosis of schizophrenia and achieve an appropriate treatment regimen to attain resolution of the patient's symptoms. This process is particularly challenging in areas of limited access to specialists a problem not only in third world countries and rural regions, but throughout the United States where there can be long waits to obtain an appointment with a psychiatrist. The present research experiment investigates a potential novel method for diagnosing schizophrenia. The overall objective of the study is to test the hypothesis that patients with schizophrenia will have a heightened tolerance to the sedating effects of anti-psychotic medications, which will be reflected in differences in their electroencephalogram (EEG) when compared to healthy normal controls. The investigators expect that the schizophrenia patients will score on the "more alert" and "less sleepy" ends of these scales, and that the normal control subjects will show the opposite response. A patient that fails to become sedated or experience the sleepiness side effects, typically caused by the anti-psychotic medication, may support the existing diagnosis of schizophrenia. Measures of the subjects' level of sedation that are found to correlate significantly with EEG response and diagnosis will be used to create a diagnostic test. This simple and inexpensive test will consist of a single dosage of anti-psychotic medication, and a rapid assessment tool with scores that have a high degree of predictive validity for the diagnosis of schizophrenia.

Overnight Thalamic TES-TI to Modulate Sleep Spindles in Individuals With Schizophrenia Spectrum Disorders and Matched Healthy Controls

This study to find out whether a type of non-invasive electrical brain stimulation called transcranial electrical stimulation with temporal interference (TES-TI) can temporarily change brain activity during sleep-especially sleep spindles (brain rhythms in the \~8-16 Hz range). The investigators are focusing on the thalamus, a deep brain region that helps coordinate brain activity during non-REM sleep. Sleep spindles are often reduced in schizophrenia, so this study is to see whether TES-TI can change spindle activity in individuals with schizophrenia spectrum disorders (SSD) and in healthy adults. To study this, a structural MRI scan will be used to customize where the stimulation electrodes are placed, and then TES-TI will be applied during one of two overnight sleep lab visits while brain activity is recorded with high-density EEG and standard sleep sensors. The other overnight is a baseline/control night during which only sham stimulation is delivered. The goal is to determine whether TES-TI during sleep can increase spindle-frequency activity in this population.

The Protein Disrupted in Schizophrenia 1 (DISC1) as a Novel Biomarker for Cardiac Disease

To study the association between DISC1 RNA expression levels and cardiac function in patients with schizophrenia.

Brain Imaging of Childhood Onset Psychiatric Disorders, Endocrine Disorders and Healthy Volunteers

Magnetic Resonance Imaging (MRI) unlike X-rays and CT-scans does not use radiation to create a picture. MRI use as the name implies, magnetism to create pictures with excellent anatomical resolution. Functional MRIs are diagnostic tests that allow doctors to not only view anatomy, but physiology and function. It is for these reasons that MRIs are excellent methods for studying the brain. In this study, researchers will use MRI to assess brain anatomy and function in X and Y chromosome variation, healthy volunteers, and patients with a variety of childhood onset psychiatric disorders. The disorders include attention deficit disorder, autism, congenital adrenal hyperplasia, childhood-onset schizophrenia, dyslexia, obsessive compulsive disorder, Sydenham's chorea, and Tourette's syndrome. Results of the MRIs showing the anatomy of the brain and brain function will be compared across age, sex (gender), and diagnostic groups. Correlations between brain and behavioral measures will be examined for normal and clinical populations....

Acetazolamide for Treatment Resistant Schizophrenia

This is a double blind adjunctive randomized controlled trial for schizophrenia using acetazolamide.

Enhancing Brain Connectivity in Schizophrenia Through Neuromodulation (Study 1)

Patients with schizophrenia spectrum disorder (SSD) will be exposed to active repetitive transcranial magnetic stimulation (rTMS) from H coil for improving white matter integrity.

Safety and Tolerability Trial of Lumateperone in Pediatric Patients With Schizophrenia, Bipolar Disorder or Autism Spectrum Disorder

This is a multicenter, global, 26-week, open-label study to assess the safety and tolerability of lumateperone in pediatric patients with schizophrenia, bipolar disorder or autism spectrum disorder.

Enhancing Brain Connectivity in Schizophrenia Through Neuromodulation (Study 2)

Patients with schizophrenia spectrum disorder (SSD) will be exposed to active repetitive transcranial magnetic stimulation (rTMS) from H coil combined with cognitive training for improving white matter integrity.

Investigation of the Effects of Angling as Supportive Therapy in Schizophrenia Treatment on Serum Parameters, Anxiety, Depression, and Quality of Life

This study aims to evaluate the effects of recreational fishing (angling) as a supportive therapeutic intervention in individuals diagnosed with schizophrenia. Schizophrenia is a chronic psychiatric disorder characterized by disturbances in thinking, perception, emotion, and behavior, often accompanied by negative symptoms such as social withdrawal, anhedonia, and cognitive impairment, which significantly reduce quality of life. Recreational activities, particularly those involving nature-based engagement, have been shown to support psychological well-being through stress reduction, improved attention, and enhanced mood regulation. Angling is considered a mindfulness-like recreational activity that promotes relaxation, concentration, and emotional regulation, potentially offering benefits for individuals with psychiatric conditions. In this randomized controlled study, participants with schizophrenia will engage in a structured recreational fishing program in addition to standard care. The effects of the intervention will be evaluated on biochemical serum parameters, anxiety and depression levels, and quality of life outcomes. The study also aims to assess the psychosocial well-being of participants and determine the feasibility of integrating angling as an adjunctive non-pharmacological intervention in schizophrenia care. The findings are expected to contribute to evidence-based complementary treatment approaches in psychiatric rehabilitation.

A Study of Brenipatide in Adult Participants With Schizophrenia

The purpose of this study is to assess the efficacy and safety of brenipatide when administered with standard of care (SoC) compared to placebo plus SoC for treatment of schizophrenia. The trial is divided into three periods as follows: Screening period will last approximately 1 month, treatment period will last a maximum of 12 months, and the follow up period will last approximately 2 months. The length of time of your study participation may last up to approximately 15 months.

A Study of the Feasibility, Safety and Tolerability of Aticaprant as Adjunctive Treatment in Participants With Schizophrenia

The purpose of this study is to see how feasible it is to enroll participants with schizophrenia and for them to complete the study/assessments. It will also assess how safe and tolerable aticaprant is when compared with placebo in participants with schizophrenia.

Study to Evaluate the Safety and Efficacy of Ublituximab in Participants With Schizophrenia

The main objective of this Phase 2 study is to assess the efficacy of ublituximab as measured by positive and negative syndrome scale (PANSS) total score in participants with schizophrenia.

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.

Exercise-based Program for Rehabilitation of Veterans With Severe Mental Illness

This is a hybrid1, effectiveness-implementation study of yoga-based exercises (YE) as an adjunctive tool for rehabilitation among persons with Severe Mental Illness (SMI). The two-arm randomized controlled trial will compare the efficacy of YE compared to the Wellness Lifestyle Program (WLP). Primary outcomes of the study will be self-report and performance-based measures of community functioning, defined in the investigators study as social, leisure, employment, and life skills functioning in the community. Secondary outcomes will include cognition and physical fitness measures.