Studies of Frontal Lobe Brain Functioning in Schizophrenia

The purpose of this work is to investigate the role of the frontal lobe, and its connections
for cognition in health and in neuropsychiatric diseases, particularly schizophrenia.
Regional cerebral blood flow (rCBF) will be measured with oxygen-15 water positron emission
tomography (PET) while subjects are either at rest or are performing a variety of
neuropsychological tests. Some of these tests involve cognitive operations that are posited
to depend upon the frontal cortex, such as the use of working memory for abstract reasoning
and problem solving, formation and maintenance of conceptual sets, set shifting, sequencing,
and delayed response; others control for nonspecific sensory and motor aspects of these
measurements or are contrast conditions posited to depend on other brain regions.
Interactions between regional activation, cognitive behavior, and neuropharmacology will be
assessed by measuring cognitively-related rCBF during treatment with drugs that may affect
frontal lobe physiology. Hypotheses about genetic determinants of these relationships will
also be tested by comparing rCBF measures across individuals harboring different genotypes
(detemined through protocol 95-M-0150).

- INCLUSION/EXCLUSION CRITERIA:

Participants in this study will reflect the diversity of the community. No one will be
excluded or discriminated against on the grounds of race, gender, religion or ethnic
background. Every attempt will be made to include women and minorities in the study
population. Children will not be studied because of radiation exposure limits on this
group.

Normal control subjects will be recruited through the NIH normal volunteer program and
through advertisement in the community and primarily through the "Genetic Study" under
protocol 95-M-0150. An additional control group of non-schizophrenic siblings of patients
with schizophrenia will also be recruited (from the community and protocol 95-M-0150, A
Neurobiological Investigation of Patients with Schizophrenia Spectrum Disorders and Their
Siblings). Control subjects will be matched to the patient groups by age, sex, and
handedness. Control subjects with history of psychiatric or neurologic disorders or medical
illnesses or surgeries that might have relevance to the investigation of brain physiology
will be excluded. Normal subjects taking medications with relevance to cerebral blood flow
and metabolism will be excluded from study.

Patients with schizophrenia will be recruited from the inpatient population of the NIMH
Wards at the NIH Clinical Center and the sibling study protocol 95-M-0150. Diagnoses will
be made by the NIMH clinical staff in accordance with DSM-IV(R). Patients with history of
neurological illness other than those of interest to the study, or other medical illness or
surgery that might have impact on the study of brain physiology, will be excluded.
Inpatients on the NIMH Schizophrenia Ward who have signed protocol 89-MH-160 "Inpatient
Evaluation of Neuropsychiatric Patients) will be studied when they have been withdrawn from
all medications for two to four weeks. They will also be studied when they are stabilized
on medication; however, no treatment decisions, for inpatients or outpatients, will be
based upon this study. All inpatients will be carefully monitored on the NIMH/NIH wards as
per protocol 89-MH-160.

Additional neuropsychiatric patients (such as those with affective disorder, Parkinson's
Disease, special genetic disorders (e.g. William's Syndrome), and other neuropsychiatric
disorders) will be recruited from the medical community, from NIH inpatient and outpatient
services, and through the National Alliance for the Mentally Ill (NAMI). Patients will be
identified by the presence of typical symptoms and signs elicited by history and
examination. Diagnoses will conform to accepted diagnostic guidelines where applicable.
Such patients will be excluded from study for 1) history of psychiatric or neurologic
disorders other than those under investigation, 2) medical illnesses or surgeries that
might have relevance to the investigation of brain physiology, 3) current medications that
are not under investigation and that have relevance to cerebral blood flow and metabolism,
and 4) IQ less than 70. Outpatients may be admitted overnight if necessary or otherwise
applicable (e.g. those from out of town).

No cognitively impaired nonschizophrenic subjects are studied in this protocol. For
Parkinsons Disease patients, information is obtained from referring physicians, from NIH
medical records for participants already enrolled in the NIH system, and by phone from the
potential participant. Further assessment is carried out by a neurologist or psychiatrist
upon arrival at the NIH. For Williams syndrome patients, IQ testing is done off-site by a
certified clinical neuropsychologist who refers patients for our study and who has followed
large numbers of these rare individuals for years.