Studies of Frontal Lobe Brain Functioning in Schizophrenia

NCT00001258 | Completed FDA Drug

• 2 other identifiers: 90001490-M-0014
• Study Type: observational
• Target: 1,039
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Healthy Subjects; Schizophrenia; Parkinson Disease

Keywords

Neuropsychology; Brain Activity; Cognitive Disorders; Prefrontal Cortex; rCBF; Psychosis; Neuroimaging; Brain Scan; PET Imaging; Schizophrenia; Natural History

Outcome Measures

Primary Outcomes (1)

• Differences between rCBF during the frontal lobe tasks and rCBF during the sensorimotor control

  ongoing

  ongoing

Study Arms (2)

1

Patients with schizophrenia spectrum disorder

Drug: Oxygen-15 Water

2

normal volunteers

Interventions

Oxygen-15 Water DRUG

1

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with schizophrenia spectrum disorder and normal volunteers

You may not qualify if:

• 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 and 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 history of psychiatric or neurologic disorders or medical illnesses or surgeries that might have relevance to the investigation of brain physiology will be excluded. Normal subjects taking medications with relevance to cerebral blood flow and metabolism will be excluded from study.
• Patients with schizophrenia will be recruited from the inpatient population of the NIMH Wards at the NIH Clinical Center and 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 who have signed protocol 89-MH-160 "Inpatient Evaluation of Neuropsychiatric Patients) will be studied when they have been withdrawn from all medications for two to four weeks. They will 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-MH-160.
• 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. 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 Parkinsons 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 neuropsychologist who refers patients for our study and who has followed large numbers of these rare individuals for years.

Sponsors & Collaborators

• National Institute of Mental Health (NIMH): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• 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.

  PMID: 1360197 BACKGROUND

• Berman 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.

  PMID: 9238064 BACKGROUND

• Mattay 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.

  PMID: 8764668 BACKGROUND

• Wei 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.

  PMID: 28416813 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Schizophrenia; Parkinson Disease; Cognitive Dysfunction; Psychotic Disorders

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Cognition Disorders; Neurocognitive Disorders

Study Officials

• Karen F Berman, M.D.

  National Institute of Mental Health (NIMH)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 1999
• First Posted: November 4, 1999
• Study Start: November 26, 1993
• Last Updated: April 29, 2026

Record last verified: 2025-09-17

Locations

US (1)