Electrophysiology and Blood Flow in Patients With Schizophrenia and Their Siblings

It is the aim of this study to investigate the functional activation and coupling between
brain regions in normals, patients with schizophrenia and unaffected family members. We will
perform electrophysiological recordings (MEG, EEG) during cognitive activation (Continuous
Performance Task, Sternberg paradigm, working memory). We will focus on the investigation of
oscillatory brain activity as this is considered to be crucial for information processing
related to neuronal integration. The measurements will be closely adapted to equivalent
fMRI-measurements presented as an independent protocol (00-M-0085). The combination of both
methods will help to improve activity source localization (MEG/EEG) and correlation of this
activity between different parts of the brain. In addition, local activity patterns (fMRI)
can be better characterized in the time domain (tonic versus phasic BOLD-activation). We will
address whether cognitive activation goes along with an increase or decrease of correlation
between regional brain areas. In this context, we will investigate whether this correlated
activation pattern is different in schizophrenics and unaffected siblings when compared with
normals. The study is integrated with the schizophrenia-sibling study (95-M-0150). Siblings
of schizophrenic patients are investigated in order to achieve a better understanding of the
genetic determination of schizophrenia-related pathophysiology.

- INCLUSION CRITERIA:

Controls:

1. 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.

2. No use of psychotropic substances in the last 3 months.

3. There is no upper age limit the lower age limit is 18 years.

Patients:

1) Schizophrenia, any subtype or schizoaffective disorder according to DSM IV, as detailed
in protocol # 89-M-0160 ("Inpatient evaluation of neuropsychiatric inpatients", Dr. Jose
Apud, principal investigator) and # 95-M-0150 ("A Longitudinal Investigation of Siblings of
Schizophrenic and Manic-Depressive Patients", Dr. Daniel R. Weinberger, principal
investigator).

EXCLUSION CRITERIA:

Controls and patients:

1. Impaired hearing.

2. Pregnancy (only for purpose of MRI procedures under separate protocols)

3. 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.

Patients:

1. 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.

2. Criteria for substance abuse met in the last 6 months.

3. Criteria for substance dependence met 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.

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

5. Concomitant medications which could interfere with performance on the task.

6. 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).