Database Registry to Examine Brain Connections and Brain Function in Mental Disorders and Neural Network Biomarkers for Relational Memory and Psychosis in Schizophrenia

The proposed project entails the collection of clinical interview data, behavioral data,
blood, magnetic resonance imaging (MRI) data, and functional magnetic resonance imaging
(fMRI) data from 1000 volunteers, both patient volunteers and healthy normal volunteers.
These data will be used for current and future investigations to better understand how the
brains of those with mental disorders process differently that brains of healthy volunteers.
The volunteers will undergo a series of clinical interviews to determine their diagnosis,
behavioral task training, medical workup, and standard structural and functional magnetic
resonance imaging. No changes will be made to the patient volunteers' medications or
treatment regimes as part of the study. Data will be collected for all volunteer groups based
on their performance on a variety of computer-mediated cognitive tasks. The volunteers will
be trained to criteria on the tasks, at which point they will have the option to complete the
MRI and fMRI portions of the study. Standard and functional MR images of the entire brain
will be acquired while volunteers perform cognitive tasks thought to activate the medial
temporal lobe and other pertinent brain regions. While participating in the task portion of
the fMRI, visual stimulation (images) will be presented via back-projection from a
high-resolution video projector (Epson 7000 series) with adjustable zoom. Volunteers will be
asked to push a button on a handheld button box to record their responses as learned during
training. For the non-task, resting portions of the fMRI, volunteers will be asked to stay
relaxed and alert. In conjunction with one of the fMRI scans we will also conduct a cerebral
blood volume (CBV) MRI to investigate blood perfusion in the medial temporal lobe of
volunteers with mental illness to compare to normal control volunteers.

The proposed project will evaluate brain connectivity during cognitive tasks, including
novelty detection, encoding and retrieval of associations between individual stimuli, and
during other cognitive tasks thought to produce abnormal fMRI activations in volunteers with
mental disorders. One example of a cognitive task is conducted as follows. Volunteers are
shown a series of one-syllable nouns and asked to internally associate a second noun to the
presented word (e.g. "station" to the presented word "train"). They press a response button
when they have made a successful word association. Subsequently, volunteers are presented
with a mixture of the previously encoded words and a new set of one-syllable nouns.
Volunteers press one response button for previously presented words and another button for
novel (new) words. fMRI scans for both parts of this task are acquired in the time between
stimulus presentation and the press of the button. In another example of a cognitive task,
volunteers are shown a novel series of faces paired with names and are instructed to remember
the name for each face. In a subsequent period, volunteers attempt to remember which name
goes to which face. The fMRI scans are acquired during both encoding and retrieval of the
face-name pairs. These two described tasks are representative of the tasks to be used in
terms of their difficulty and the effort required of the volunteers. In addition, "resting"
and "control" tasks will be used to establish a baseline of brain activity against which we
may then compare activity during our task of interest. Volunteers will receive instructions
on task performance and will practice tasks prior to scanning in order to eliminate the
novelty of the task itself as a potential confound. While the appointment time for a scan may
take several hours, the volunteer will be in the scanner between 60 and 120 minutes depending
on the specific memory task that is being administered at that visit. Any volunteer may
receive training and be scanned on more than one task, but no volunteer will be kept in the
scanner for longer than 120 minutes in any given session. Volunteers may also be asked to
undergo one or two 60-minute MR Spectroscopy scans conducted on the 3Tesla (3T) or 7Tesla
(7T) scanner. In this scan we will measure the levels of different brain compounds, such as
neurotransmitters (e.g. glutamate, gamma aminobutyric acid [GABA]) or endogenous brain
metabolites (e.g., N-acetyl -aspartate)in various brain regions, to non-invasively study
tissue biochemistry.

Inclusion Criteria:

Volunteers with Schizophrenia or other mental illness

- Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision
(DSM-IV-TR) diagnosis of Schizophrenia or Schizoaffective disorder

- Competent to give informed consent

- All races and ethnicities

- Eyesight corrected to 20-40 or better

- Able to read, speak, and understand English

Healthy volunteers

- No past or current severe mental illness

- All races and ethnicities

- Eyesight corrected to 20-40 or better

- Able to read, speak, and understand English

Exclusion Criteria:

Volunteers with schizophrenia or other mental illness

- Diagnosis of an organic brain disease

- Diagnosis of DSM-IV-TR alcohol or substance abuse within the last month or DSM-IV-TR
alcohol or substance dependence within the last three months

- Serious, unstable medical illness

- History of serious head injury

- Pregnant women

Healthy volunteers

- History of psychiatric illness

- Current use of psychoactive drugs excluding nicotine and caffeine

- Diagnosis of an organic brain disease

- Serious, unstable medical illness

- History of serious head injury

- Pregnant women