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Transforming the understanding
and treatment of mental illnesses.


Schizophrenia is a chronic and severe mental disorder that affects how a person thinks, feels, and behaves. People with schizophrenia may seem as though they have lost touch with reality. They may experience symptoms such as hearing voices that are not heard by others or believing that other people are reading their minds, controlling their thoughts, or plotting to harm them. Although schizophrenia is not as common as other mental disorders, the symptoms can cause serious interference in daily life. 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.

Neurocognition After Perturbed Sleep

Study Type: Interventional
Start Date: September 30, 2021
Location: New York, New York
Eligibility: Ages 18–50, Does Not Accept Healthy Volunteers

Individuals with schizophrenia display a wide range of neurocognitive difficulties resulting in functional impairment and disability. Extensive evidence indicates insomnia and sleep disturbances play a substantial role in degrading cognitive functioning. However, the putative impact of insomnia and sleep disturbances on neurocognition and daily functioning has not been investigated in people with schizophrenia. The goal of this study is to characterize sleep in individuals with schizophrenia and quantify its impact on neurocognition and daily functioning.

Safety, Tolerability, and Pharmacokinetics of Switching From Oral Risperidone to Risperidone Implant

Study Type: Interventional
Start Date: March 30, 2021
Location: Long Beach, California
Eligibility: Ages 18–55, Does Not Accept Healthy Volunteers

This is an Open-Label Study in Stable Schizophrenia Patients to Evaluate the Safety, Tolerability, and Pharmacokinetics of Switching from Oral Risperidone to Risperidone Implant (DLP-114).

Glutamatergic Mechanisms of Psychosis and Target Engagement (SA1)

Study Type: Interventional
Start Date: January 1, 2021
Location: New York, New York
Eligibility: Ages 18–55, Accepts Healthy Volunteers

50 healthy volunteers (HV) will participate in 2 identical ketamine-induced pharmacoBOLD (phBOLD) sessions at least 7 days apart. On both days, clinical assessments will be performed following removal of the subject from the scanner.

HV will be discharged home after clearance by the study physician. This study will assign ketamine doses in successive 10 subject cohorts. The ketamine dose for the 1st cohort will start at 0.08 mg/kg. For subsequent cohorts, the bolus will be successively reduced or increased by 0.02 mg/kg (n=10/dose) to determine the lowest dose of ketamine that still produces a robust phBOLD response.

The study will be subject and rater blind, i.e. subjects and raters, will be blinded to the treatment (ketamine dose) group.

The study physician will be aware of the ketamine dose, and ketamine dose will be the same for both sessions.

Subjects will not be told what the exact ketamine dose they will receive, but it will be based on their weight and will be no higher than 0.08 mg/kg.

Medial-prefrontal Enhancement During Schizophrenia Systems Imaging

Study Type: Interventional
Start Date: November 12, 2020
Location: San Francisco, California
Eligibility: Ages 18–60, Accepts Healthy Volunteers

This randomized controlled trial in healthy controls (HC) and patients with schizophrenia (SZ) aims to examine 1) the underlying cognitive and neural cause of self-agency deficits in SZ; 2) the responsiveness to a novel navigated repetitive transcranial magnetic stimulation (nrTMS) target in the medial prefrontal cortex (mPFC); and 3) how modulation of mPFC activity impacts the larger self-agency network to mediate changes in self-agency judgments. Our overall hypothesis is that increased mPFC excitability by active high-frequency nrTMS in HC and SZ will induce behavioral improvements in self-agency and neural changes in the larger self-agency network that will generalize to improvements in overall cognition, symptoms and daily functioning, and will likely lead to the development of new effective neuromodulation therapies in patients with schizophrenia.

Impact of Inflammation on Reward Circuits, Motivational Deficits and Negative Symptoms in Schizophrenia

Study Type: Interventional
Start Date: August 31, 2020
Location: Atlanta, Georgia
Eligibility: Ages 18–59, Does Not Accept Healthy Volunteers

This study will recruit persons with schizophrenia or schizoaffective disorder and will use an oral glucose tolerance test to test the hypothesis that insulin resistance drives inflammation.

Early-Phase Schizophrenia: Practice-based Research to Improve Outcomes

Study Type: Observational
Start Date: April 1, 2020
Location: Lauderdale Lakes, Florida
Eligibility: Ages 15–40,

The goal if the project is to develop a learning health network devoted to the treatment of first episode psychosis.

Models of Auditory Hallucination

Study Type: Interventional
Start Date: February 27, 2020
Location: New Haven, Connecticut
Eligibility: Ages 18–45, Does Not Accept Healthy Volunteers

The purpose of this study is to address the shortcoming in clinical hallucination research by causally manipulating the neural loci of conditioned hallucination task behavior in-person in patients with psychosis using transcranial magnetic stimulation (TMS), tracking the impact of this manipulation on the number of times participants with hallucinations report hearing tones that were not presented. With such a causal intervention, the veracity of this explanation of hallucinations will be either validated or disconfirmed. If validated, the task can be further developed as a biomarker for predicting the hallucination onset, guiding, developing or tracking the effects of treatments for hallucinations.

Multi-modal Assessment of Gamma-aminobutyric Acid (GABA) Function in Psychosis

Study Type: Interventional
Start Date: January 16, 2020
Location: Ann Arbor, Michigan
Eligibility: Ages 16–60, Accepts Healthy Volunteers

The purpose of this study is to better understand mental illness and will test the hypotheses that while viewing affective stimuli, patient groups will show increased blood oxygenation level dependent (BOLD) signal by fMRI after lorazepam.

This study will enroll participants between the ages of 16 and 60, who have a psychotic illness (such as schizophrenia, bipolar disorder, and schizoaffective disorder). The study will also enroll eligible participants without any psychiatric illness, to compare their brains.

The study will require participants to have 3-4 sessions over a few weeks. The first session (may be over two visits) will include a diagnostic interview and several questionnaires (qols) to assess eligibility. Subsequently, there will will be two separate functional magnetic resonance imaging (fMRI) sessions in which lorazepam or placebo will be given prior to the MRI. During the fMRI the participants will also be asked to answer questions. Additionally, the participants will have their blood drawn, women of child bearing potential will have a urine pregnancy test, vital signs taken, and asked to complete more qols.

Targeting Physical Health in Schizophrenia: Physical Activity Can Enhance Life Randomized Control Trial

Study Type: Interventional
Start Date: December 20, 2019
Location: Chapel Hill, North Carolina
Eligibility: Ages 18–65, Does Not Accept Healthy Volunteers

Purpose: To test the effectiveness of an exercise intervention that combines group walking, activity tracking, and heart rate monitoring (i.e. Physical Activity can Enhance Life, PACE-Life) on the physical and mental health for individuals with schizophrenia spectrum disorder.

Participants: 56 individuals with schizophrenia spectrum disorders.

Procedures (methods): During the baseline assessment, which can be completed virtually and in-person (based on participant preference) all participants will be provided with a Fitbit wristband and instructed how to use it. During the first group session, participants will be taught how to use their heart rate (on the Fitbit) to determine how fast participants should walk (to achieve the appropriate exercise dosage). Information on proper care, usage, and how to determine the appropriate heart rate from the watch, to guide the intensity of the walk, will be provided to participants and reviewed at each group session. Participants randomly assigned to the PACE Life virtual walking group sessions will meet the other group members and group leaders and be reminded of the heart rate (HR) that corresponds with the intensity of that group session. Next, the group will exercise for 15 minutes in the first two weeks, progressing to 30-minute walking sessions over the course of the intervention. At the completion of the sessions, everyone will take a break for water and review the walk. After the second group session of each week, participants will receive weekly progress reports of their steps and minutes spent walking the prior week (obtained from Fitbit devices). During this session, participants will also set individual goals for the upcoming week for both their "intensity walks" and total steps per day.

Participants randomly assigned to Fitbit Alone will be given a Fitbit and shown how to use it by study staff. Participants will also be given information on current recommended physical activity guidelines (150 min/week of moderate intensity exercise) and will be told that study staff may be contacting them on a weekly basis (or shorter, if necessary) if it looks like participants are not wearing their Fitbit for a certain number of days (e.g. 3 consecutive days) or to troubleshoot any issues. If necessary, participants might be invited to meet with research staff to get assistance on any Fitibit or exercise-related issues.

Promoting Activity and Cognitive Enrichment in Schizophrenia (PACES)

Study Type: Interventional
Start Date: October 1, 2019
Location: Pittsburgh, Pennsylvania
Eligibility: Ages 18–60, Does Not Accept Healthy Volunteers

This project will conduct a confirmatory efficacy trial of two novel psychosocial interventions, Cognitive Enhancement Therapy and Enriched Supportive Therapy, for the treatment of persistent negative symptoms in schizophrenia.

Maximizing the Impact of Neuroplasticity Using Transcranial Electrical Stimulation Study 2

Study Type: Interventional
Start Date: July 1, 2019
Location: Minneapolis, Minnesota
Eligibility: Ages 18–60, Does Not Accept Healthy Volunteers

Non-invasive neuromodulation, such as transcranial direct current stimulation ( tDCS) , is emerging as an important therapeutic tool with documented effects on brain circuitry, yet little is understood about h ow it changes cognition. In particular, tDCS may have a critical role to play in generalization, that is how training in one domain generalizes to unlearned or unpracticed domains. This problem has resonance for disorders with cognitive deficits, such as schizophrenia.

Understanding how tDCS affects brain circuity is critical to the design and application of effective interventions, especially if the effects are different for healthy vs. psychiatric populations. In previous research, one clue to the mechanism underlying increased learning and generalization with tDCS was provided by neuroimaging data from subjects with schizophrenia undergoing cognitive training where increases in thalamocortical (prefrontal) functional connectivity (FC) predicted greater generalization.

The premise of this proposal is that increases in thalamocortical FC are associated with the generalization of cognitive training, and tDCS facilitates these increases. The overarching goals of this proposal are to deploy neuroimaging and cognitive testing to understand how tDCS with cognitive training affect thalamocortical circuitry in individuals with and without psychosis and to examine variability in response within both groups.

Study 1 will compare right prefrontal, left prefrontal and sham tDCS during concurrent cognitive training over 12 weeks in 90 healthy controls. Study 2 will be similar in all aspects but will examine 90 patients with schizophrenia or schizoaffective disorder and include clinical assessments. Results of the study will provide crucial information about location of stimulation, length of treatment, modeled dosage, trajectory and durability needed to guide future research and interventions for cognitive impairments.

Cognitive Adaption Training-Effectiveness in Real-world Settings and Mechanism of Action (CAT-EM)

Study Type: Interventional
Start Date: April 4, 2019
Locations: Dayville, Connecticut; Lauderdale Lakes, Florida; Granite City, Illinois; Lawrenceburg, Indiana; Manchester, New Hampshire; Eugene, Oregon; Providence, Rhode Island
Eligibility: Ages 18–65, Does Not Accept Healthy Volunteers

The investigators propose a cluster randomized effectiveness trial comparing Cognitive Adaptation Training (CAT; a psychosocial treatment using environmental supports such as signs, alarms, pill containers, checklists, technology and the organization of belongings established in a person's home or work environment to bypass the cognitive and motivational difficulties associated with schizophrenia ) to existing community treatment (CT) for individuals with schizophrenia in 8 community mental health centers across multiple states including 400 participants. Mechanisms of action will be examined. Participants will be assessed at baseline and 6 and 12 months on measures of functional and community outcome, medication adherence, symptoms, habit formation and automaticity, cognition and motivation.

Mobile CBT for Negative Symptoms

Study Type: Interventional
Start Date: January 18, 2019
Location: La Jolla, California
Eligibility: Ages 18–60, Does Not Accept Healthy Volunteers

This randomized controlled clinical trial will test a combined group contact plus mobile CBT-informed skills training intervention targeting defeatist attitudes in consumers with schizophrenia in comparison to a supportive contact control group in order to change motivational negative symptoms linked to defeatist attitudes.

Improving Cognition Via Exercise in Schizophrenia

Study Type: Interventional
Start Date: April 26, 2018
Location: 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. Also, people with schizophrenia are at increased risk for suicide, with approximately 40-50% of individuals attempting to take their own lives during their lifetime. The goal of the proposed study is to examine the impact of exercise training on cognition, suicide risk, daily functioning, and biomarkers of cognitive change and suicidality in people with schizophrenia.

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 participants' brains respond to food images as well as asking questions about their food preferences and intake and clinical symptoms. The investigators may also ask participants to complete an exercise or diet intervention to see how this changes brain responses or food preferences.

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, 5) Post-Traumatic Stress Disorder 6) Opioid Use Disorder 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.

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: November 13, 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: March 15, 2002
Location: Bethesda, Maryland
Eligibility: Ages 18–90, 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.

Magnetic Resonance Imaging (MRI) of Neuropsychiatric Patients and Healthy Volunteers

Study Type: Observational
Start Date: February 17, 2000
Location: Bethesda, Maryland
Eligibility: Ages 18 and Older, Accepts Healthy Volunteers

The purpose of this study is to use brain imaging technology to compare differences in brain structure, chemistry, and functioning in individuals with brain and mental disorders compared to healthy volunteers.

Schizophrenia is a brain disorder that results from subtle changes and abnormalities in neurons. These deficits likely occur in localized regions of the brain and may result in widespread, devastating consequences. The neuronal abnormalities are inherited through a complex combination of genetic and environmental factors. Brain imaging technologies can be used to better characterize brain changes in individuals with schizophrenia. This study will use magnetic resonance imaging (MRI) scans to identify predictable, quantifiable abnormalities in neurophysiology, neurochemistry and neuroanatomy that characterize schizophrenia and other neurological and neuropsychiatric disorders.

Genetic Study of Schizophrenia

Study Type: Observational
Start Date: July 15, 1995
Location: Bethesda, Maryland
Eligibility: Ages 18–55, 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....

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

Study Type: Observational
Start Date: June 19, 1990
Location: Bethesda, Maryland
Eligibility: Ages 3 and Older, Accepts 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.

Inpatient Evaluation of Adults With Schizophrenia

Study Type: Observational
Start Date: September 15, 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.