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Schizophrenia is a devastating brain disorder — the most chronic and disabling of the severe mental illnesses. People with schizophrenia often suffer terrifying symptoms such as hearing internal voices not heard by others, or believing that other people are reading their minds, controlling their thoughts, or plotting to harm them. These symptoms may leave them fearful and withdrawn. Learn more about Schizophrenia.

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Featured Studies

Featured studies include only those currently recruiting participants. Studies with the most recent start date appear first.

Procedures for Sample Acquisition and Distribution for The Human Brain Collection Core

Study Type: Observational
Start Date: November 21, 2018
Location: Bethesda, Maryland
Eligibility: Ages N/A–120, Does Not Accept Healthy Volunteers


The Human Brain Collection Core (HBCC) collects brain and other tissues. They get these from deceased people who may or may not have had psychiatric disorders. The next of kin gives permission for researchers to get the tissues. Researchers want to collect medical details of people whose brains are donated. They also want to use the donated tissue to study brain chemistry and structure. This could lead to better treatments for mental illness.


To create a collection of human brain tissue to learn about the causes and mechanisms of mental disorders.


People willing to donate their deceased relative s brain tissue. The deceased person could not have had any of the following:

Severe mental retardation

Long-lasting seizure disorder

Infections that affect the brain


Brain damage

Being on a respirator for more than 12 hours

Major sepsis

Serious renal or hepatic disease

Certain dementias and degenerative diseases


Medical Examiner s Offices will screen donors who have recently died. Some others will be screened by hospitals or funeral homes.

Participants will be the next of kin. They will give consent for HBCC to obtain brain tissue from the deceased person. The tissue will be frozen for future research.

Participants will have a 30-minute phone call. They will answer questions about the deceased person s medical and psychiatric conditions. They will answer questions about the person s use of medicines and drugs.

Participants will be contacted by a social worker. They will be asked for permission to access the deceased person s medical records.

Improving Accessibility and Personalization of CR for Schizophrenia

Study Type: Interventional
Start Date: July 16, 2018
Locations: Brooklyn, New York; New York, New York
Eligibility: Ages 18–65, Does Not Accept Healthy Volunteers

This project will explore adaptations of treatments for schizophrenia, with the goal of optimizing their effectiveness in real-world clinical settings and readiness for broad deployment. Schizophrenia is associated with cognitive deficits that negatively impact essential areas of daily functioning. NY State Office of Mental Health (OMH) is the first and largest state system of care to implement a statewide program of cognitive remediation (CR), an evidence-based practice for improving cognition and aiding functional recovery. Through Cognitive Remediation to Promote Recovery (CR2PR), CR is now offered in outpatient programs, with plans to expand to more services and further adapt implementation to improve treatment outcomes. This project will work directly with OMH clinics and clinicians to build upon and improve current CR delivery methods. This project will study the impact of two adaptations. One focuses on increasing the accessibility of the program, which participants report is limited by the requirement of twice weekly attendance. This project will compare the feasibility and acceptability of delivering CR in either two clinic-based sessions (Clinic) or one clinic and one remote session (Hybrid) per week. Qualitative interviews will be conducted with stakeholders to explore the impact of the adaptation. The second adaptation is intended to improve personalization of CR by systematically accounting for individual differences in neurocognitive needs. Drawing upon convergent evidence for tailoring CR based on need for early auditory processing (EAP) training, this project examines whether integrating a measure of EAP into the current baseline assessment facilitates personalization of the menu of restorative computer-based exercises used in CR. Feasibility parameters and qualitative/quantitative data analyses of facilitators and barriers to Hybrid CR delivery will together inform further treatment refinement and the design of a larger effectiveness trial of Clinic versus Hybrid CR. This project will examine how EAP assessment is employed by practitioners to personalize the CR treatment plan and examine if EAP improvement is associated with cognitive outcomes in public practice CR settings. Finally cognitive, functional, and service use outcomes in Hybrid versus Clinic CR will be compared.

Improving Cognition Via Exercise in Schizophrenia

Study Type: Interventional
Start Date: April 26, 2018
Locations: Stanford, California; Augusta, Georgia; New York, New York; Chapel Hill, North Carolina
Eligibility: Ages 18–55, Does Not Accept Healthy Volunteers

People with schizophrenia display a broad range of cognitive impairments that have been identified as major determinants of poor functioning and disability. The goal of the proposed study is to examine the impact of exercise training on cognition, daily functioning, and biomarkers of cognitive change in people with schizophrenia.

Glutamate Reducing Interventions in Schizophrenia

Study Type: Interventional
Start Date: April 17, 2018
Location: New York, New York
Eligibility: Ages 18–30, Does Not Accept Healthy Volunteers

Participants will be administered several doses of POMA (low and high doses) over 14 days to individuals at clinical high risk for developing psychosis and use MRI brain imaging to determine whether these doses of POMA are affecting glutamate levels.

Texting for Relapse Prevention

Study Type: Interventional
Start Date: March 12, 2018
Location: Baltimore, Maryland
Eligibility: Ages 18 and Older, Accepts Healthy Volunteers

The purpose of this study is to examine whether Texting for Relapse Prevention (T4RP), a text messaging-based early warming for relapse prevention in people who have schizophrenia/SAD, is associated with fewer relapse symptoms compared to a treatment-as-usual control group.

Neurofeedback Training for High Risk Psychosis

Study Type: Interventional
Start Date: March 1, 2018
Location: Hartford, Connecticut
Eligibility: Ages 12–25, Does Not Accept Healthy Volunteers

Young people who are at great risk for developing psychosis have cognitive deficits which are strongly related to functioning in the community. This study looks to target a specific cognitive skill called processing speed to see if improving the ability to process information in a timely manner will improve social function in adolescents and young adults at risk for developing schizophrenia. Half will receive neurofeedback cognitive training targeting processing speed while the other half will receive an active control.

Targeting Auditory Hallucinations With Alternating Current Stimulation

Study Type: Interventional
Start Date: November 14, 2017
Location: Chapel Hill, North Carolina
Eligibility: Ages 18–70, Does Not Accept Healthy Volunteers

Investigating the effects of non-invasive transcranial alternating current stimulation (tACS) as a treatment for auditory hallucinations in patients with schizophrenia.

Biomarkers of Conversion Risk and Treatment Response in Early-Stage Schizophrenia

Study Type: Interventional
Start Date: September 15, 2017
Location: New York, New York
Eligibility: Ages 18–35, Accepts Healthy Volunteers

Schizophrenia (SZ) is a highly debilitating neuropsychiatric disorder of young adulthood onset and a leading cause of disability worldwide. While treatments delivered at early stages of the disorder may be effective at reducing psychosis or altering the course of the disease, there are currently no biomarkers capable of identifying subjects in early stages of SZ who are likely to respond to treatment and would be good candidates for available proactive, symptomatic or future disease-modifying treatments; or those who would not respond and can be spared unnecessary medication exposure. The lack of these vitally important biomarkers provides a compelling rationale for the present multidisciplinary research project, which aims to develop and validate highly promising noninvasive and objective proton magnetic resonance spectroscopy (1H MRS)-based biomarkers for monitoring treatment response in early stages of SZ. In support of the viability of this overall objective is a large body of data, reported by the applicants and others, that show (a) that levels of glutamate (Glu) and - aminobutyric acid (GABA) - respectively, the major excitatory and inhibitory amino acid neurotransmitter systems - are abnormally elevated in medication-naïve and unmedicated first episode and chronic SZ patients; (b) that the effect of treatment with antipsychotic medications in these populations may be to lower or normalize brain levels of both Glu and GABA. To investigate the potential of these in vivo brain Glu and GABA abnormalities to serve as biomarkers of treatment response in early-stage SZ, the applicants propose to use 1H MRS to measure Glu and GABA levels in the largest cohort of medication-free SZ subjects to date, at baseline and following 4 weeks of antipsychotic treatment.

Lifestyle Intervention for Young Adults With Serious Mental Illness

Study Type: Interventional
Start Date: March 1, 2017
Locations: Cambridge, Massachusetts; Manchester, New Hampshire
Eligibility: Ages 18–35, Does Not Accept Healthy Volunteers

This is a four year project evaluating the effectiveness of a group-based lifestyle intervention (PeerFIT) supported by mobile health (mHealth) technology and social media compared to Basic Education in fitness and nutrition supported by a wearable Activity Tracking device (BEAT) in achieving clinically significant improvements in weight loss and cardiorespiratory fitness in young adults with serious mental illness (SMI).

Clinical Trial of AVL-3288 in Schizophrenia Patients

Study Type: Interventional
Start Date: November 30, 2016
Location: New York, New York
Eligibility: Ages 18–50, Does Not Accept Healthy Volunteers

Single-center, outpatient, randomized, double-blind, placebo-controlled, 3-treatment-phase, cross-over study to evaluate the safety, tolerability and efficacy of two oral doses of AVL-3288 each compared to placebo, in patients with schizophrenia.

Targeting Stress Reactivity in Schizophrenia: Integrated Coping Awareness Therapy

Study Type: Interventional
Start Date: October 3, 2016
Locations: Carrboro, North Carolina; Raleigh, North Carolina
Eligibility: Ages 15–35, Does Not Accept Healthy Volunteers

To test the feasibility of a clinical trial implementing I-CAT, a novel therapeutic intervention combining strategies to improve stress reactivity and increase meaningful coping, as well as a range of possible proximal (e.g. autonomic, endocrine, immune indices of stress reactivity, symptom severity) and distal measures (function, relapse, quality of life) for 40 people with first episode psychosis in the context of a small randomized controlled trial.

Targeted Cognitive Training in Clinical High Risk (CHR) for Psychosis

Study Type: Interventional
Start Date: March 31, 2015
Location: Cambridge, Massachusetts
Eligibility: Ages 15–30, Does Not Accept Healthy Volunteers

This project is a randomized-controlled trial to test the efficacy of computer-based targeted cognitive training (TCT) versus a placebo intervention of commercial computer games in adolescent/young adults at clinical high risk (CHR) for psychosis. TCT is designed to optimize learning-induced neuroplasticity in vulnerable neurocognitive systems. A main aim is to test the hypothesis that this neuroscience-guided TCT intervention will improve neural function, and that these neural improvements will improve cognition and functional outcome. CHR participants will be randomly assigned to 40 hours of TCT or placebo computer games completed within 10 weeks. TCT consists of 20 hours of training in cognition, including processing speed, memory, attention, and cognitive control followed by 20 hours of training in social cognition including affect recognition and theory of mind. Neuroimaging, cognition, social cognition, clinical symptoms, and functional status will be assessed at baseline, after 20 hours/5 weeks of cognitive training (mid-intervention), and after 20 hours/5 weeks of social-cognitive training (post-intervention). Cognition, social cognition, symptoms, and functioning will also be assessed at a 9 month follow-up (i.e. 9 months after intervention completion). We predict that TCT will lead to improvements in neurocognitive function and functional status. The results of this study will provide important information about a benign, non-pharmacological intervention for improving cognition and functional outcome in CHR individuals.

Tryptophan MRI in People With Schizophrenia and Healthy Controls

Study Type: Interventional
Start Date: September 30, 2014
Location: Catonsville, Maryland
Eligibility: Ages 18–55, Accepts Healthy Volunteers

Kynurenic acid (KYNA) is a naturally occurring chemical in the brain. Studies with rodents indicate that levels of KYNA can impact levels of the neurotransmitters glutamate and dopamine. One way to reliably increase KYNA levels is by ingesting the amino acid tryptophan. Tryptophan is a normal part of the human diet. Tryptophan gets metabolized/changed to other chemicals in the body- including KYNA. By giving people 6 grams of tryptophan, the investigators will be able to increase the KYNA level in a controlled way. The investigators will then be able to study the effects of KYNA on neurotransmitters by using cognitive tests and magnetic resonance imaging techniques (measuring brain activity and brain chemistry using the MRI magnet). They will test people using tryptophan and also using a placebo to look for differences. The investigators will test healthy controls and people with schizophrenia to look for differences.

Neuronal Effects of Exercise in Schizophrenia

Study Type: Interventional
Start Date: August 31, 2014
Location: Aurora, Colorado
Eligibility: Ages 21–70, Does Not Accept Healthy Volunteers

This study plans to learn more about how common drugs prescribed to individuals with schizophrenia contribute to weight gain, as well as how exercise and diet impact appetite and the brain's response to food. In this study, the investigators will be evaluating how patients' brains respond to food images as well as asking questions about their food preferences and intake and clinical symptoms. The investigators may also ask patients to complete an exercise or diet intervention to see how this changes brain responses or food preferences.

Oral Risperidone Versus Injectable Paliperidone Palmitate for Treating First-Episode Schizophrenia

Study Type: Interventional
Start Date: October 31, 2011
Location: Los Angeles, California
Eligibility: Ages 18–45, Accepts Healthy Volunteers

This study will determine the efficacy of oral risperidone (Risperdal) versus long-acting injectable paliperidone palmitate (Invega Sustenna) in treating people with first-episode schizophrenia.

Neural Oscillations as Genetic and Functional Biomarkers in Normal and Disease States

Study Type: Observational
Start Date: January 31, 2011
Location: Baltimore, Maryland
Eligibility: Ages 14–62, Accepts Healthy Volunteers

The principle aim of the project is to analyze brain electrical activity and genetic information that will help identify the nature and cause of the disease schizophrenia. This effort should lay the groundwork for future treatment in schizophrenic patients.

Imaging Cannabinoid Receptors Using Positron Emission Tomography (PET) Scanning

Study Type: Observational
Start Date: July 31, 2010
Location: New Haven, Connecticut
Eligibility: Males, Ages 18–55, Accepts Healthy Volunteers

The aim of the present study is to assess the availability of cannabinoid receptors (CB1R) in the human brain. CB1R are present in everyone's brain, regardless of whether or not someone has used cannabis. The investigators will image brain cannabinoid receptors using Positron Emission Tomography (PET) imaging and the radioligand OMAR, in healthy individuals and several conditions including 1) cannabis use disorders, 2) psychotic disorders, 3) prodrome of psychotic illness and 4) individuals with a family history of alcoholism, using the PET imaging agent or radiotracer, [11C]OMAR. This will allow us to characterize the number and distribution of CB1R in these conditions. It is likely that the list of conditions will be expanded after the collection of pilot data and as new data on cannabinoids receptor function and psychiatric disorders becomes available.

Those in the cannabis us disorder arm of the study will have a PET scan on at least three occasions: once while smoking as usual, once after 48-hours of abstinence from cannabis, and a final time after 4 weeks of abstinence. Additional scans may be conducted within the 4 weeks and the last scan may be conducted well beyond 4 weeks. Similarly, while most schizophrenia patients may get scanned just once, a subgroup of patients may get scanned more than once. For example to tease out the effects of medications, unmedicated patients may get scanned while unmedicated and again after treatment with antipsychotic medications. Similarly prodromes may get scanned while in the prodromal stage off medications, on medications and after conversion to schizophrenia.

Database Registry to Examine Brain Connections and Brain Function in Mental Disorders and Neural Network Biomarkers for Relational Memory and Psychosis in Schizophrenia

Study Type: Observational
Start Date: March 31, 2010
Location: Dallas, Texas
Eligibility: Ages 18–60, Accepts Healthy Volunteers

Several observations have been made with magnetic resonance imaging (MRI) that characterize brain connections and brain function in individuals with schizophrenia and other mental disorders. For example, research investigating schizophrenia focuses on the dysfunction of connections within and between the medial temporal lobe and the prefrontal cortex as well as other pertinent brain regions. This database registry will allow for the collection of clinical interview data, behavioral data, blood, magnetic resonance imaging (MRI) data, and functional magnetic resonance imaging (fMRI) data on individuals with and without mental disorders to better understand how connections in the brain and various brain regions function differently while volunteers perform various cognitive tasks. This is an observational study that is being conducted to collect data and place it in a registry for current and future investigational questions related to imaging in mental disorders.

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

Study Type: Observational
Start Date: July 17, 2009
Location: Bethesda, Maryland
Eligibility: Ages 18–90, Accepts Healthy Volunteers


- 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.


- To study the amount and distribution of two types of dopamine receptors.


- Individuals between the ages of 18 and 60 who have schizophrenia.

- Healthy volunteers between the ages of 18 and 90.


- 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.

PET Scanning in Parkinson s Disease

Study Type: Observational
Start Date: September 17, 2001
Location: Bethesda, Maryland
Eligibility: Ages 18 and Older, Accepts Healthy Volunteers

This is an in vivo positron emission tomography (PET) study of regional cerebral dopamine and blood flow in normal volunteers, persons with Parkinson s disease (both familial and sporadic), and those with schizophrenia spectrum disorders. The latter also sign consent for NIH approved protocol 89-M-0160, "Inpatient Evaluation of Neuropsychiatric Patients," PI: Daniel Eisenberg, M.D. Using PET with 6-[F-18] Fluoro-L-dopa (FDOPA) and (15)0-H2O in a single scan session, both presynaptic dopaminergic function and regional cerebral blood flow (rCBF) are assessed. The kinetic rate constant (Ki) for presynaptic dopaminergic uptake in striatum and other regions is calculated. We compare Ki across subject groups and relate the findings to rCBF. Findings are also related to allelic variation in genes of interest, for determination of which participants sign separate consent for NIH approved protocol 95-M-0150 Neurobiological Investigation of Patients with Schizophrenia Spectrum Disorders and Their Siblings, PI: Karen F. Berman, MD. We also draw comparisons between subjects with inherited vs. sporadic Parkinson s disease to determine whether the PET phenotype is the same in both groups, and we compare system-level, circuit-based pathophysiology across PD and schizophrenia groups. Each subject is further screened with an MRI to rule out structural abnormalities and also to further delineate areas of interest in the PET scans....

Genetic Study of Schizophrenia

Study Type: Observational
Start Date: July 6, 1995
Location: Bethesda, Maryland
Eligibility: Ages 18 and Older, Accepts Healthy Volunteers

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.

Inpatient Evaluation of Adults With Schizophrenia

Study Type: Observational
Start Date: September 13, 1989
Location: Bethesda, Maryland
Eligibility: Ages 18 and Older, Does Not Accept Healthy Volunteers

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.

Evaluation of the Genetics of Bipolar Disorder

Study Type: Observational
Start Date: August 4, 1980
Location: Bethesda, Maryland
Eligibility: Ages 18–85, Does Not Accept Healthy Volunteers

This study looks to identify genes that may affect a person's chances of developing bipolar disorder (BP) and related conditions.