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.
This protocol is meant to provide a matrix for multiple, simultaneous brain imaging
investigations using magnetic resonance imaging (MRI). 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
- INCLUSION CRITERIA:
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.
Schizophrenia, any subtype or schizoaffective disorder according to DSM IV, as detailed in
protocol # 89-M-0160 ("Inpatient Evaluation of Neuropsychiatric Inpatients") and #95-M-0150
("A Longitudinal Investigation of Siblings of Schizophrenic and Manic-Depressive
Bipolar Disorder with Psychotic Features according to DSM IV as detailed in protocol.
Menstrually-Related Mood Disorder.
Mild to Moderate Parkinson's Disease (Hoehn and Yahr Stage 1-3).
CONTROLS AND PATIENTS:
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.
Coexistence of another major mental illness at the time of the study. If the patients
experienced other mental illnesses in the past (e.g. major depression), then this should be
judged to be fully recovered.
Criteria for substance abuse met in the last 6 months.
Criteria for substance dependence in the last year. If criteria for dependence were met in
the past, then the duration of the disorder was less than 3 years, or not judged to have
produced long-term brain changes to allow the patient to be in the study.
Major concurrent medical illness likely to interfere with the acquisition of the task.
Concomitant medications which could interfere with performance on the task.
Presence of dyskinetic movements of the face and tongue (likely to interfere with eyeblink
measures, or of gross involuntary movements of the whole body (likely to interfere with
positioning in the MRI scanner).