Healthy SubjectsNCT00001258
Studies of Frontal Lobe Brain Functioning in Schizophrenia
An observational study of Healthy Subjects and Schizophrenia, run by National Institute of Mental Health (NIMH) at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Healthy Subjects, Schizophrenia, Parkinson Disease
- What is being tested?
- Oxygen-15 Water
- How many people
- 1,039 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Nov 1993to not given
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with schizophrenia spectrum disorder and normal volunteers
Who may be able to join
- Participants in this study will reflect the diversity of the community. No one will be excluded or discriminated against on the grounds of race, gender, religion or ethnic background. Every attempt will be made to include women and minorities in the study population. Children will not be studied because of radiation exposure limits on this group.
- Normal control subjects will be recruited through the NIH normal volunteer program, through advertisement in the community and primarily through the "Genetic Study" under protocol 95-M-0150. An additional control group of non-schizophrenic siblings of patients with schizophrenia will also be recruited (from the community and protocol 95-M-0150, A Neurobiological Investigation of Patients with Schizophrenia Spectrum Disorders and Their Siblings). Control subjects will be matched to the patient groups by age, sex, and handedness. Control subjects with a history of psychiatric or neurologic disorders or medical illnesses or surgeries that might have relevance to the investigation of brain physiology will be excluded. Control subjects requiring continuous treatment with prescribed medications that impact cerebral blood flow and metabolism will be excluded. Control subjects unable to refrain from nicotine or caffeine for at least 4 hours or alcohol for at least 12 hours prior to the PET study will be excluded. Control subjects with exposure to other substances with relevance to cerebral blood flow and metabolism, such as some over-the-counter medications, will be reviewed in each individual case, to ensure that an adequate period of abstinence will precede the performance of the PET study.
- Patients with schizophrenia spectrum disorder will be recruited from the inpatient population of the NIMH Wards at the NIH Clinical Center and from the sibling study protocol 95-M-0150. Diagnoses will be made by the NIMH clinical staff in accordance with DSM-IV(R). Patients with history of neurological illness other than those of interest to the study, or other medical illness or surgery that might have impact on the study of brain physiology, will be excluded. Inpatients on the NIMH Schizophrenia Ward will have signed protocol 89-M-0160 ("Inpatient Evaluation of Neuropsychiatric Patients") and will be studied after being free of neuroleptic treatment for at least two weeks. They may also be studied when they are stabilized on medication; however, no treatment decisions, for inpatients or outpatients, will be based upon this study. All inpatients will be carefully monitored on the NIMH/NIH wards as per protocol 89-M-0160.
- Additional neuropsychiatric patients (such as those with affective disorder, Parkinson's Disease, special genetic disorders (e.g. William's Syndrome), and other neuropsychiatric disorders) will be recruited from the medical community, from NIH inpatient and outpatient services, and through the National Alliance for the Mentally Ill (NAMI). Patients will be identified by the presence of typical symptoms and signs elicited by history and examination. Diagnoses will conform to accepted diagnostic guidelines where applicable. Such patients will be excluded from study for 1) history of psychiatric or neurologic disorders other than those under investigation, 2) medical illnesses or surgeries that might have relevance to the investigation of brain physiology, 3) current medications that are not under investigation and that have relevance to cerebral blood flow and metabolism, and 4) IQ less than 70. Patients unable to refrain from nicotine or caffeine for at least 4 hours or alcohol for at least 12 hours prior to the PET study will be excluded. Patients with exposure to other substances with relevance to cerebral blood flow and metabolism, such as some over-the-counter medications, will be reviewed in each individual case, to ensure that an adequate period of abstinence will precede the performance of the PET study. Outpatients may be admitted overnight if necessary or otherwise applicable (e.g. those from out of town).
- No cognitively impaired nonschizophrenic subjects are studied in this protocol. For Parkinson's Disease patients, information is obtained from referring physicians, from NIH medical records for participants already enrolled in the NIH system, and by phone from the potential participant. Further assessment is carried out by a neurologist or psychiatrist upon arrival at the NIH. For Williams syndrome patients, IQ testing is done off-site by a certified clinical neurophysiologist who refers patients for our study and who has followed large numbers of these rare individuals for years.
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: Studies of Frontal Lobe Function During Cognitive Stimulation as Measured With Oxygen-15 Water Positron Emission Tomography in Normal Subjects and Patients With Neuropsychiatric Disorders
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.
Read the detailed description
The purpose of this work is to investigate the role of the frontal lobe and its connections for cognition in health and in neuropsychiatric diseases, particularly schizophrenia. Regional cerebral blood flow (rCBF) will be measured with oxygen-15 water positron emission tomography (PET) while subjects are either at rest or are performing a variety of neuropsychological tests. Some of these tests involve cognitive operations that are posited to depend upon the frontal cortex, such as the use of working memory for abstract reasoning and problem solving, formation and maintenance of conceptual sets, set shifting, sequencing, and delayed response; others control for nonspecific sensory and motor aspects of these measurements or are contrast conditions posited to depend on other brain regions. Interactions between regional activation, cognitive behavior, and neuropharmacology will be assessed by measuring cognitively-related rCBF during treatment with drugs that may affect frontal lobe physiology. Hypotheses about the genetic determinants of these relationships will also be tested by comparing rCBF measures across individuals harboring different genotypes (determined through protocol 95-M-0150).
- Conditions
- Healthy Subjects, Schizophrenia, Parkinson Disease
- Being tested
- Oxygen-15 Water
- Keywords
- Neuropsychology, Brain Activity, Cognitive Disorders, Prefrontal Cortex, rCBF, Psychosis, Neuroimaging, Brain Scan, PET Imaging, Schizophrenia, Natural History
- Medical subject headings
- Schizophrenia, Parkinson Disease, Cognitive Dysfunction, Psychotic Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oxygen-15 WaterDrug
| Study group | Role | What they receive |
|---|---|---|
| 1 | Patients with schizophrenia spectrum disorder Receives: Drug: Oxygen-15 Water | |
| 2 | normal volunteers |
What is being measured
The primary outcome is the main question the study is designed to answer.
Differences between rCBF during the frontal lobe tasks and rCBF during the sensorimotor control
ongoing
Measured: ongoing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 1999 (estimated)
- Study start26 Nov 1993
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Healthy SubjectsStudies of the same condition, open and under way.
- More trials run by National Institute of Mental Health (NIMH)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 1,039 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute of Mental Health (NIMH)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Karen F Berman, M.D., Principal investigator, National Institute of Mental Health (NIMH)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00001258
- Sponsor's protocol ID
- 900014
- Other IDs
- 90-M-0014
- Status last verified
- 10 Aug 2026
- First submitted
- 3 Nov 1999
- Last updated
- 29 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Berman KF, Torrey EF, Daniel DG, Weinberger DR. Regional cerebral blood flow in monozygotic twins discordant and concordant for schizophrenia. Arch Gen Psychiatry. 1992 Dec;49(12):927-34. doi: 10.1001/archpsyc.1992.01820120015004.
PubMed 1360197Berman KF, Schmidt PJ, Rubinow DR, Danaceau MA, Van Horn JD, Esposito G, Ostrem JL, Weinberger DR. Modulation of cognition-specific cortical activity by gonadal steroids: a positron-emission tomography study in women. Proc Natl Acad Sci U S A. 1997 Aug 5;94(16):8836-41. doi: 10.1073/pnas.94.16.8836.
PubMed 9238064Mattay VS, Berman KF, Ostrem JL, Esposito G, Van Horn JD, Bigelow LB, Weinberger DR. Dextroamphetamine enhances "neural network-specific" physiological signals: a positron-emission tomography rCBF study. J Neurosci. 1996 Aug 1;16(15):4816-22. doi: 10.1523/JNEUROSCI.16-15-04816.1996.
PubMed 8764668Wei SM, Baller EB, Kohn PD, Kippenhan JS, Kolachana B, Soldin SJ, Rubinow DR, Schmidt PJ, Berman KF. Brain-derived neurotrophic factor Val66Met genotype and ovarian steroids interactively modulate working memory-related hippocampal function in women: a multimodal neuroimaging study. Mol Psychiatry. 2018 Apr;23(4):1066-1075. doi: 10.1038/mp.2017.72. Epub 2017 Apr 18.
PubMed 28416813
Study at a glance
From the registry record, last updated by the sponsor on 29 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Studies of Frontal Lobe Function During Cognitive Stimulation as Measured With Oxygen-15 Water Positron Emission Tomography in Normal Subjects and Patients With Neuropsychiatric Disorders
- ClinicalTrials.gov ID
- NCT00001258
- Acronym / sponsor ID
- 900014
- Conditions
- Healthy Subjects, Schizophrenia, Parkinson Disease
- Keywords
- Neuropsychology, Brain Activity, Cognitive Disorders, Prefrontal Cortex, rCBF, Psychosis, Neuroimaging, Brain Scan
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 1,039 participants (actual)
- Lead sponsor
- National Institute of Mental Health (NIMH)US National Institutes of Health
- Study start
- 26 Nov 1993 (actual)
- First posted
- 4 Nov 1999 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The purpose of this work is to investigate the role of the frontal lobe and its connections for cognition in health and in neuropsychiatric diseases, particularly schizophrenia. Regional cerebral blood flow (rCBF) will be measured with oxygen-15 water positron emission tomography (PET) while subjects are either at rest or are performing a variety of neuropsychological tests. Some of these tests involve cognitive operations that are posited to depend upon the frontal cortex, such as the use of working memory for abstract reasoning and problem solving, formation and maintenance of conceptual sets, set shifting, sequencing, and delayed response; others control for nonspecific sensory and motor aspects of these measurements or are contrast conditions posited to depend on other brain regions. Interactions between regional activation, cognitive behavior, and neuropharmacology will be assessed by measuring cognitively-related rCBF during treatment with drugs that may affect frontal lobe physiology. Hypotheses about the genetic determinants of these relationships will also be tested by comparing rCBF measures across individuals harboring different genotypes (determined through protocol 95-M-0150).
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | – | Drug: Oxygen-15 WaterPatients with schizophrenia spectrum disorder |
| 2 | – | –normal volunteers |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with schizophrenia spectrum disorder and normal volunteers
Key inclusion criteria (5 listed)
- Participants in this study will reflect the diversity of the community. No one will be excluded or discriminated against on the grounds of race, gender, religion or ethnic background. Every attempt will be made to include women and minorities in the study population. Children will not be studied because of radiation exposure limits on this group.
- Normal control subjects will be recruited through the NIH normal volunteer program, through advertisement in the community and primarily through the "Genetic Study" under protocol 95-M-0150. An additional control group of non-schizophrenic siblings of patients with schizophrenia will also be recruited (from the community and protocol 95-M-0150, A Neurobiological Investigation of Patients with Schizophrenia Spectrum Disorders and Their Siblings). Control subjects will be matched to the patient groups by age, sex, and handedness. Control subjects with a history of psychiatric or neurologic disorders or medical illnesses or surgeries that might have relevance to the investigation of brain physiology will be excluded. Control subjects requiring continuous treatment with prescribed medications that impact cerebral blood flow and metabolism will be excluded. Control subjects unable to refrain from nicotine or caffeine for at least 4 hours or alcohol for at least 12 hours prior to the PET study will be excluded. Control subjects with exposure to other substances with relevance to cerebral blood flow and metabolism, such as some over-the-counter medications, will be reviewed in each individual case, to ensure that an adequate period of abstinence will precede the performance of the PET study.
- Patients with schizophrenia spectrum disorder will be recruited from the inpatient population of the NIMH Wards at the NIH Clinical Center and from the sibling study protocol 95-M-0150. Diagnoses will be made by the NIMH clinical staff in accordance with DSM-IV(R). Patients with history of neurological illness other than those of interest to the study, or other medical illness or surgery that might have impact on the study of brain physiology, will be excluded. Inpatients on the NIMH Schizophrenia Ward will have signed protocol 89-M-0160 ("Inpatient Evaluation of Neuropsychiatric Patients") and will be studied after being free of neuroleptic treatment for at least two weeks. They may also be studied when they are stabilized on medication; however, no treatment decisions, for inpatients or outpatients, will be based upon this study. All inpatients will be carefully monitored on the NIMH/NIH wards as per protocol 89-M-0160.
- Additional neuropsychiatric patients (such as those with affective disorder, Parkinson's Disease, special genetic disorders (e.g. William's Syndrome), and other neuropsychiatric disorders) will be recruited from the medical community, from NIH inpatient and outpatient services, and through the National Alliance for the Mentally Ill (NAMI). Patients will be identified by the presence of typical symptoms and signs elicited by history and examination. Diagnoses will conform to accepted diagnostic guidelines where applicable. Such patients will be excluded from study for 1) history of psychiatric or neurologic disorders other than those under investigation, 2) medical illnesses or surgeries that might have relevance to the investigation of brain physiology, 3) current medications that are not under investigation and that have relevance to cerebral blood flow and metabolism, and 4) IQ less than 70. Patients unable to refrain from nicotine or caffeine for at least 4 hours or alcohol for at least 12 hours prior to the PET study will be excluded. Patients with exposure to other substances with relevance to cerebral blood flow and metabolism, such as some over-the-counter medications, will be reviewed in each individual case, to ensure that an adequate period of abstinence will precede the performance of the PET study. Outpatients may be admitted overnight if necessary or otherwise applicable (e.g. those from out of town).
- No cognitively impaired nonschizophrenic subjects are studied in this protocol. For Parkinson's Disease patients, information is obtained from referring physicians, from NIH medical records for participants already enrolled in the NIH system, and by phone from the potential participant. Further assessment is carried out by a neurologist or psychiatrist upon arrival at the NIH. For Williams syndrome patients, IQ testing is done off-site by a certified clinical neurophysiologist who refers patients for our study and who has followed large numbers of these rare individuals for years.
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Oxygen-15 Water | Drug | 1 |
Primary outcome
Differences between rCBF during the frontal lobe tasks and rCBF during the sensorimotor control
Time frame: ongoing
ongoing
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Oct 2026.
- Background: PubMed 1360197Berman KF, Torrey EF, Daniel DG, Weinberger DR. Regional cerebral blood flow in monozygotic twins discordant and concordant for schizophrenia. Arch Gen Psychiatry. 1992 Dec;49(12):927-34. doi: 10.1001/archpsyc.1992.01820120015004.
- Background: PubMed 9238064Berman KF, Schmidt PJ, Rubinow DR, Danaceau MA, Van Horn JD, Esposito G, Ostrem JL, Weinberger DR. Modulation of cognition-specific cortical activity by gonadal steroids: a positron-emission tomography study in women. Proc Natl Acad Sci U S A. 1997 Aug 5;94(16):8836-41. doi: 10.1073/pnas.94.16.8836.
- Background: PubMed 8764668Mattay VS, Berman KF, Ostrem JL, Esposito G, Van Horn JD, Bigelow LB, Weinberger DR. Dextroamphetamine enhances "neural network-specific" physiological signals: a positron-emission tomography rCBF study. J Neurosci. 1996 Aug 1;16(15):4816-22. doi: 10.1523/JNEUROSCI.16-15-04816.1996.
- Derived from this study: PubMed 28416813Wei SM, Baller EB, Kohn PD, Kippenhan JS, Kolachana B, Soldin SJ, Rubinow DR, Schmidt PJ, Berman KF. Brain-derived neurotrophic factor Val66Met genotype and ovarian steroids interactively modulate working memory-related hippocampal function in women: a multimodal neuroimaging study. Mol Psychiatry. 2018 Apr;23(4):1066-1075. doi: 10.1038/mp.2017.72. Epub 2017 Apr 18.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
Related trials for Healthy Subjects
RecruitingPhase 1
A Study of INI-822 in Healthy Volunteers and Participants With Metabolic Dysfunction-Associated Steatohepatitis (MASH) or Presumed MASH
Metabolic Dysfunction-Associated Steatohepatitis
Not yet recruitingPhase 1
Phase I Trial of High-Density Theta Burst Stimulation (hdTBS)
Healthy Volunteers
Not yet recruiting
Stearic Acid and Endothelial Function
Healthy Middle-aged Subjects, Obesity & Overweight
Not yet recruitingPhase 1
A Study of Zovaglutide (ZT002 Injection) in Participants With Hepatic Impairment and Healthy Participants
Overweight, Obesity
Not yet recruitingObservational study
Assessing the Impact of Perceptions of Unpredictability on Objective Measures of Food Consumption and Metabolism
Healthy Volunteer, Obestity
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Karen F Berman, M.D. principal investigator
National Institute of Mental Health (NIMH)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Healthy Subjects and Schizophrenia, run by National Institute of Mental Health (NIMH) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Differences between rCBF during the frontal lobe tasks and rCBF during the sensorimotor control (time frame: ongoing). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00001258, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Oct 2026.