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

Structural and Functional Imaging of Neuropsychiatric Patients and Normal Volunteers With 3.0 Tesla MRI and Magnetoencephalography (MEG)

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.

Study Overview

• Status: Recruiting
• Conditions: Schizophrenia; Normal Physiology

Detailed Description

This protocol is meant to provide a matrix for multiple, simultaneous brain imaging investigations using magnetic resonance imaging (MRI) at 3.0 Tesla (3T). We intend to study regional brain structure, physiology, and biochemistry in living human subjects, both healthy and ill. Based on multiple clinical, neuropathological, and functional neuroimaging studies, it is clear that schizophrenia is a brain disorder arising from subtle neuronal deficits (for lack of more specific terminology). These deficits likely arise in a few key regions such as dorsolateral prefrontal cortex and hippocampal formation, that result in widespread, multifaceted, and devastating clinical consequences. These neuronal deficits are clearly heritable, although in a complex fashion from multiple genes interacting in an epistatic fashion with each other and the environment. We hypothesize that these neuronal deficits, clearly resulting in quantifiable behavioral abnormalities in schizophrenic patients, will produce predictable, quantifiable aberrations in neurophysiology that we can "map" using magnetic resonance imaging. In spite of numerous functional imaging findings, clinical applications remain scarce and pathognomonic findings absent. Therefore, we do not anticipate that an approach based solely on any one modality is likely to significantly advance our knowledge base. Instead, we propose to create brain imaging datasets for individual human subjects predicated on 1) the appraisal of brain function from multiple domains simultaneously; 2) the characterization of brain function via summation and intercorrelation of these data; and 3) the digestion of these data based on the parsing of complex clinical phenomenology into quantifiable neurophysiological parameters. Thus, in addition to the identification of those parameters that best characterize and identify manifest schizophrenia (i.e., state variables), we hypothesize that some of these fundamental characteristics will be heritable. These fundamental characteristics, so-called endo- or intermediate phenotypes, represent powerful tools to find susceptibility genes and have already generated a number of linkage findings.

• Study Type: Observational
• Enrollment (Estimated): 3420

Contacts and Locations

• Study Contact: Name: Bobby Das; Phone Number: (301) 435-4593; Email: bdas@ln.nimh.nih.gov
• Study Contact Backup: Name: Michael D Gregory, M.D.; Phone Number: (301) 402-1371; Email: gregorymd@mail.nih.gov

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • Recruiting
      • National Institutes of Health Clinical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Patients with schizophrenia and healthy subjects from the community.

Description

• INCLUSION CRITERIA:

CONTROLS:

No psychiatric or severe chronic medical illness at the time of the study, and by history. This includes the absence of substance abuse histories, learning disabilities and all DSM IV disorders. The investigators will evaluate medical histories and medical conditions that are judged not to interfere with the study may be allowed.

No use of psychotropic substances in the last 3 months.

There is no upper age limit. The lower age limit is 18 years.

Controls will all have the capacity to consent.

PATIENTS:

Schizophrenia, any subtype or schizo-affective disorder according to DSM IV .

Bipolar Disorder with Psychotic Features according to DSM IV.

Menstrually-Related Mood Disorder.

Mild to Moderate Parkinson's Disease (Hoehn and Yahr Stage 1-3).

Williams Syndrome (partial or full) with IQ in the normal range.

Patients with Multiple Sclerosis.

EXCLUSION CRITERIA:

CONTROLS AND PATIENTS:

Impaired hearing.

Pregnancy.

Head trauma with loss of consciousness in the last year, or any evidence of functional impairment due to and persisting after head trauma.

Patients or healthy volunteers with a known risk from exposure to high magnetic fields (e.g. patients with pace makers) and those who have metallic implants (e.g. braces) in the head region (likely to create artifact on the MRI scans) will be excluded from participating in the fMRI studies.

History of any (excepting nicotine-related) DSM5-defined moderate to severe substance use disorder (or DSM-IV-defined substance dependence).

Cumulative lifetime history of any (excepting nicotine-related) DSM5-defined mild substance use disorder (or any DSM-IV-defined substance abuse), either in excess of 5 years total or not in remission for at least 6 months.

NIMH employees and staff and their immediate family members will be excluded from the study per NIMH policy.

Non-NIMH NIH employees and staff may participate and will be given the NIH Frequently Asked Questions (FAQs) for NIH Staff Who are Considering Participation in NIH Research.

PATIENTS:

Coexistence of another major mental illness at the time of the study. If the patients experienced other mental illnesses in the past (e.g. a learning disability or major depression), then this should be judged to be fully recovered.

Major concurrent medical illness likely to interfere with the acquisition of the task.

Concomitant medications which could interfere with performance on the task.

Involuntary movements that interfere with positioning in the MRI scanner).

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Healthy volunteers; Healthy subjects from the community
Schizophrenia; Patients with schizophrenia and psychosis
Williams Syndrome; Individuals with copy number variation in the Williams Syndrome Region

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
fMRI BOLD responses	Group differences between patients with schizophrenia and healthy subjects, also genotyping used to characterize subjects as well.	MRI study completion
magnetic field potentials	Group differences in MEG signal for patients with schizophrenia and healthy subjects.	MEG
brain volumetric measures	VBM and cortical parcellation are used in schizophrenia and healthy controls.	VBM
regional MRSI measures	GABA and glutamate measurements in schizophrenia and healthy controls.	spectroscopy
DTI anisotropy measures	Compare fractional anisotropy and other measures of white matter connectivity for schizophrenic patients and controls.	DTI

Secondary Outcome Measures

Outcome Measure
neuropsychological task performance data

Collaborators and Investigators

• Sponsor: National Institute of Mental Health (NIMH)
• Investigators: Principal Investigator: Michael D Gregory, M.D., National Institute of Mental Health (NIMH)

Publications and helpful links

General Publications

• Marenco S, Meyer C, van der Veen JW, Zhang Y, Kelly R, Shen J, Weinberger DR, Dickinson D, Berman KF. Role of gamma-amino-butyric acid in the dorsal anterior cingulate in age-associated changes in cognition. Neuropsychopharmacology. 2018 Oct;43(11):2285-2291. doi: 10.1038/s41386-018-0134-5. Epub 2018 Jul 3.
• Jabbi M, Cropp B, Nash T, Kohn P, Kippenhan JS, Masdeu JC, Mattay R, Kolachana B, Berman KF. BDNF Val66Met polymorphism tunes frontolimbic circuitry during affective contextual learning. Neuroimage. 2017 Nov 15;162:373-383. doi: 10.1016/j.neuroimage.2017.08.080. Epub 2017 Sep 1.
• 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.
• Jabbi M, Chen Q, Turner N, Kohn P, White M, Kippenhan JS, Dickinson D, Kolachana B, Mattay V, Weinberger DR, Berman KF. Variation in the Williams syndrome GTF2I gene and anxiety proneness interactively affect prefrontal cortical response to aversive stimuli. Transl Psychiatry. 2015 Aug 18;5(8):e622. doi: 10.1038/tp.2015.98.
• Jabbi M, Kohn PD, Nash T, Ianni A, Coutlee C, Holroyd T, Carver FW, Chen Q, Cropp B, Kippenhan JS, Robinson SE, Coppola R, Berman KF. Convergent BOLD and Beta-Band Activity in Superior Temporal Sulcus and Frontolimbic Circuitry Underpins Human Emotion Cognition. Cereb Cortex. 2015 Jul;25(7):1878-88. doi: 10.1093/cercor/bht427. Epub 2014 Jan 23.

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): February 17, 2000
• Primary Completion: December 7, 2022
• Study Completion: December 7, 2022

Study Registration Dates

• First Submitted: February 15, 2000
• First Submitted That Met QC Criteria: February 15, 2000
• First Posted (Estimated): February 16, 2000

Study Record Updates

• Last Update Posted (Actual): March 27, 2024
• Last Update Submitted That Met QC Criteria: March 26, 2024
• Last Verified: November 21, 2023

More Information

Terms related to this study

• Keywords: Schizophrenia; Natural History; Magnetic Resonance Imaging; fMRI; Cognition; MEG
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia
• Other Study ID Numbers: 000085; 00-M-0085

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No