Schizophrenia is a complex and heritable disorder that encompasses several clinical symptom
domains and functional impairments. Existing treatments of schizophrenia, although effective
against positive symptoms, fail to benefit negative symptoms, the focus of the current
protocol. One of the strategies of novel drug development depends on identifying heritable
physiological deficits that mark the disease liability and are thought to occur along the
causal pathway of negative symptoms. These heritable physiological deficits are often found
in the biological relatives of schizophrenia proband; particularly those who have
schizophrenia related personality styles [defined by schizophrenia spectrum personalities
(SSP) in the diagnostic system], even though they do not have the full-blown illness. The
current protocol will pilot a strategy of targeting biomarkers of negative symptoms using
intranasal oxytocin in relatives of schizophrenia patients. The drug probe studies in such
non-clinical sample have several advantages including the absence of other drug treatment
that may modulate the response, and the lack of generalized deficits causing problems with
task comprehension/engagement that may mute the therapeutic signal. In addition, finding of
efficacy of the experimental drug on the target physiological deficit and the associated
symptoms has clinical implications on its own rights. This is because about 25% of subjects
with schizophrenia spectrum personality disorders experience serious functional impairments.
Oxytocin is an extensively used drug, which is well tolerated with few serious side effects.
Several lines of evidence suggest its putative role in the treatment of negatives symptoms,
particularly a lack of social drive and related symptoms.
The current study will examine the effects of intranasal oxytocin on physiological/cognitive
markers of negative symptoms in 24 participants with schizophrenia spectrum traits. Subjects
will be tested in two one-day studies carried out at least a month apart. Subjects will
receive a 24 IU dose of intranasal oxytocin (or placebo) followed by a battery of
cognitive/neurophysiological tests administered 50 minutes later completed over the next 155
minutes. A second dose of the drug (oxytocin or placebo) will be administered 2 hours after
the 1st in order to maintain therapeutic plasma levels and to complete all testing.
- Male/Female subjects between ages of 18-64 years
- The presence of 3 or more SSP symptoms (at least 2 of the SSP symptoms will be
negative symptoms as defined by the schizoid traits)
- The presence of visuo-spatial working memory impairment as defined by error in the
oculomotor delayed response (ODR) task of more than 0.5 SD above the mean values in
healthy control subjects
- Relative of an individual with schizophrenia, schizo-affective, or schizophreniform
- Able to provide written informed consent. Females are excluded due to risk of
discomfort and unblinding due to potential uterine cramps induced by oxytocin.
- Subjects meeting criteria for a life-time diagnosis of any one of the DSM IV, Axis I
psychotic disorders (exceptions being a single past episode of major depressive
disorder with psychotic features or psychotic symptoms associated with substance abuse
with the substance abuse ending 6-months prior to study participation) (this is for
the SSP recruitment)
- Subjects meeting DSM-IV criteria for current alcohol or substance dependence (other
than nicotine) within the last 6 months or DSM-IV criteria for alcohol or substance
abuse (other than nicotine) within the last month
- Medical conditions that preclude participation in drug trials or assessments of
outcome measures (including significant brain, cardiac, liver, lung, endocrinological
or metabolic disorders)
- Received any investigational drug in the preceding four weeks.