Bethesda, Maryland 20892

  • Normal Physiology


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 summary:

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 pathognomic 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. Precis of Substudy: Effects of prosocial neuropeptides on human brain function The goal of this substudy is to delineate neural systems involved in fear processing, emotional memory, and cognition reactive to intranasally applied prosocial neuropeptides (oxytocin, vasopressin) as a prelude to defining genetic variation in humans impacting on this circuit.


- 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. 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. 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).



Primary Contact:

Principal Investigator
Karen F Berman, M.D.
National Institute of Mental Health (NIMH)

Bobby Das
Phone: (301) 435-4593

Backup Contact:

Karen F Berman, M.D.
Phone: (301) 496-7603

Location Contact:

Bethesda, Maryland 20892
United States

Bobby Das, M.S.
Phone: 301-435-4593

Site Status: Recruiting

Data Source:

Date Processed: June 21, 2021

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