Effects of Oxytocin Nasal Spray on Social Affiliation
Condition: Schizophrenia
MeSH terms: Schizophrenia
Intervention: Oxytocin; Placebo
Intervention description: 24 IU oxytocin (or Placebo) in a total of 6 puffs (3 puffs per nostril); Single dose (plus a booster dose) drug probe study using intranasal placebo
Intervention MeSH terms: Oxytocin
Phase: Phase 2
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 27.0
Sex: All
Minimum age: 18 Years
Maximum age: 64 Years
Healthy volunteers: No
Keywords: Schizophrenia; Eye movements; phenotype; biochemical; relatives

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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
             disorder

          -  Able to provide written informed consent. Females are excluded due to risk of
             discomfort and unblinding due to potential uterine cramps induced by oxytocin.

        Exclusion Criteria:

          -  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.