Brain Blood Flow Changes Elicited by Oxytocin in Volunteers With and Without Schizophrenia

Schizophrenia is a severely debilitating psychiatric disorder that afflicts approximately 1%
of the population (American Psychiatric Association, 1994) and is a serious public health
problem. The specific mechanism of schizophrenia remains unknown. Affective responsivity and
adaptive social behaviors are fundamental impairments in people with schizophrenia. These
features have a detrimental impact on function in many areas of daily life. Unfortunately,
the brain mechanisms that underlie these problems are still not understood. This study will
use positron emission tomography (PET) and regional cerebral blood flow (rCBF) measures to
ascertain the timing (1.5 hour period) of OT action on absolute regional brain activity in
schizophrenia (SZ) and healthy control (HC) subjects. Particular focus will be on the
amygdala, ventral striatum, anterior hippocampus and hypothalamus (neural regions involved
in affliative behavior). Subjects will be studied with intranasally administered oxytocin
and placebo while at rest and while making judgments about emotional faces. This approach
will tell us to what extent the amygdala and limbic system's physiological response to
oxytocin is predictive of a subject's behavioral sensitivity to this neuropeptide. The
elucidation of this information may have a significant impact on predicting functional
outcome and novel drug treatments in schizophrenia.

Functional magnetic resonance imaging (MRI) studies show that oxytocin modulates the
amygdala's response during social and emotional decisions. When administered intranasally,
OT may be beneficial for the treatment of negative symptoms in schizophrenia by enhancing a
person's affiliative behavior and diminishing distrust. It is not, however, known to what
extent intranasal oxytocin modifies regional neurotransmission and human brain metabolism.
There are at present no studies in animals or humans specifically examining the time course
action of OT on whole brain activity.

Inclusion Criteria:

- Normal volunteers: Age range: 18-55 years of age

- Normal Volunteers: No psychiatric illness in self; no psychotic illness in first
degree relatives

- Normal Volunteers: No previous history of substance dependence in last 6 months; no
substance abuse in last month

- Normal Volunteers: No contraindication for MRI scanning (i.e. cardiac pacemaker,
prosthesis)

- Normal Volunteers: Not pregnant

- Normal Volunteers: No major medical illness (e.g. seizure disorder) or medication
that affects brain structure (e.g. steroids)

- Normal Volunteers: Participation in Healthy Subject Recruitment protocol
(HP-00042350).

- Patient Volunteers: DSM-IV diagnosis of schizophrenia

- Patient Volunteers: Voluntary and competent to sign an informed consent

- Patient Volunteers: No contraindication for MRI scanning (i.e. cardiac pacemaker,
prosthesis)

- Patient Volunteers: No previous history of substance dependence in last 6 months; no
substance abuse in last month

- Patient Volunteers: Not pregnant

- Patient Volunteers: No major medical illness other than schizophrenia that affects
brain structure (e.g. seizure disorder); not currently taking medication other than
that for schizophrenia that affects brain structure (e.g. steroids)

- Patient Volunteers: No diagnosis of Major Depressive Disorder within last 6 months

- Patient Volunteers: SANS Asociality global score 2 or greater

- Patient Volunteers: No change in antipsychotic medication (type and dose) within the
last 4 weeks

- Patient volunteers: Age range: 18-55 years of age

Exclusion Criteria:

- Normal Volunteers: Age outside of specified range -Normal Volunteers: Psychiatric
illness in self; psychotic illness in first- degree relative

- Normal Volunteers: Previous history of substance dependence in last 6 months;
substance abuse in last month

- Normal Volunteers: Contraindication for MRI scanning (i.e. cardiac pacemaker,
prosthesis)

- Normal Volunteers: Pregnant

- Normal Volunteers: Major medical illness (e.g. seizure disorder) or medication that
affects brain structure (e.g. steroids)

- Patient Volunteers: Age outside of specified range

- Patient Volunteers: Contraindication for MRI scanning (i.e. cardiac pacemaker,
prosthesis)

- Patient Volunteers: History of substance dependence in last 6 months; substance abuse
in last month

- Patient Volunteers: Pregnancy

- Patient Volunteers: Major medical illness other than schizophrenia that affects brain
structure; currently taking medication other than that for schizophrenia that affects
brain structure

- Patient Volunteers: Diagnosis of Major Depressive Disorder within last 6 months

- Patient Volunteers: SANS Asociality global score < 2

- Patient Volunteers: Change in antipsychotic medication (type and dose) within the
last 4 weeks