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

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).