Oxytocin as Adjunctive Treatment of Schizophrenia
Condition: Schizophrenia
MeSH terms: Schizophrenia
Intervention: Oxytocin; Placebo; Control
Intervention description: OT intervention will be administration of OT intranasally at a dose of three 4 IU puffs per nostril for a total dose of 24 IU. This dose has been used in a number of other similarly designed challenge studies examining the effects of a single dose of OT (Kirsch et al. 2005; Kosfeld et al. 2005; Guastella et al. 2008a; Guastella et al. 2008b; Rimmele et al. 2009; Andari et al. 2010).; The PBO/control will consist of the OT vehicle only delivered as 3 puffs of saline per nostril for a total of 6 puffs. Each puff contains 0.1 ml in volume, so the total delivered will be 0.6 ml intranasally.; Participants who have no psychiatric diagnosis and will be controls for this project. These controls will NOT receive oxytocin or PBO. They will only receive psychiatric screening interview, MCCB Consensus Cogntive Battery assessment, urine drug screen, vision testing, and the three social cognition tasks.
Intervention MeSH terms: Oxytocin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 39.0
Sex: Male
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      The focus of the current project is to advance our understanding of the effects of oxytocin
      (OT) on components of social cognition in schizophrenia (SCZ). Despite the rapid increase in
      our understanding of the role of OT in rodent models of social behavior and an explosion of
      interest in the prosocial effects of OT in healthy controls, little work has been done to
      dissect the potential effects of OT on SCZ subjects with social deficits. Social deficits are
      a crucial aspect of the functional impairments that limit the rehabilitation of patients with
      SCZ. In particular, SCZ patients with enduring negative symptoms (deficit syndrome,
      Kirkpatrick et al. 1989) have prominent social deficits as a core feature of this subtype of
      the illness. Our currently available medications do very little to improve these social
      deficits. Hence it is of utmost public health importance to address the knowledge gap
      regarding the potential of OT to improve social function in this illness. Intact social
      function depends on the competent functioning of several cognitive domains that subserve
      perception of social cues and the generation of motivated social behavior. We propose to
      conduct a pharmacological challenge study of OT vs. placebo administration to study the
      effects of OT on specific components of social cognition in male deficit syndrome SCZ
      subjects.

      Primary Hypothesis: Intranasal OT will improve social cognition in subjects with deficit
      syndrome SCZ.
    

Eligibility criteria:

        Subjects for the study will be forty male VA patients with a diagnosis of schizophrenia.
        Diagnosis will be determined using the Structured Clinical Interview for DSM-IV Axis I
        Disorders/SCID-P (Spitzer et al. 1992). Subjects must be categorized as having a primary
        deficit syndrome on the Kirkpatrick Schedule for the Deficit Syndrome (Kirkpatrick et al.
        1989).

        Additional inclusion criteria:

          1. Subjects must be between 18 and 65 years old at the time of study screening.

          2. Subjects must demonstrate adequate decisional capacity, in the judgment of the
             consenting study staff member, to make a choice about participating in this research
             study.

          3. Subjects must have been psychiatrically and medically stable for 8 weeks prior to
             consent in the judgment of the Principal Investigator.

          4. Subjects must have been maintained on a stable treatment of antipsychotics and/or
             other concomitant psychotropic treatment for at least 6 weeks prior to consent.

          5. Subjects must have no more than a moderate severity rating on hallucinations and
             unusual thought content as shown by a score of ≤ 4 on the Positive and Negative
             Symptoms Scale (PANSS).

          6. Subjects must be able to validly complete the Measurement and Treatment Research to
             Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB), in
             the judgment of the consenting study staff person.

          7. Subjects must have the visual, auditory, and motor capacity to use the computer
             software in the judgment of the consenting study staff person. Visual acuity must be
             at least 20/30 corrected.

          8. Subjects must have a minimal level of extrapyramidal symptoms as shown by a
             Simpson-Angus Scale total score of no more than 6.

          9. Subjects must have a minimal level of depressive symptoms as shown by a Calgary
             Depression Scale (CDSS) total score of no more than 10.

        Exclusion criteria:

          1. Female sex

          2. History of bipolar disorder

          3. Active substance dependence within the prior 30 days (cigarette smoking is allowed)

          4. Has had a psychiatric hospitalization in the 8 weeks prior to consent.

          5. Suicidal or homicidal ideation in the previous six months

          6. Subjects who have answered 'yes' to Question 5 (Active Suicidal Ideation with Specific
             Plan and Intent) on the Columbia-Suicide Severity Rating Scale, C-SSRS, or who have
             answered 'yes' to any of the suicide-related behaviors (actual attempt, interrupted
             attempt, aborted attempt, preparatory act or behavior) on the C-SSRS "Suicidal
             Behavior" portion shall be excluded from the study if ideation or behavior occurred
             within one month of consent. Subjects excluded for this reason will be referred for
             appropriate treatment.

          7. History of mental retardation or pervasive developmental disorder

          8. History of neurological disorder (e.g., traumatic brain injury, seizure disorder,
             Parkinson's Disease, dementia), loss of consciousness for more than 10 minutes due to
             head trauma, known HIV infection, or AIDS

          9. Treatment with a benzodiazepine in the two weeks prior to consent.

        Control Participants:

        Inclusion Criteria:

          -  Male

          -  Ages 18-65

        Exclusion Criteria:

          -  Female

          -  History of a psychotic disorder, or depression requiring medication

          -  Active substance abuse or dependence within the prior 30 days

          -  Medical admission within the past six months

        Criteria to rule out subjects with medical problems likely to present a confound:

          -  Known HIV infection or AIDS

          -  History of TBI

          -  Seizure disorder

          -  Known Alzheimer's Disease or other dementia

          -  Minimal cognitive impairment (MCI)

          -  Parkinson's Disease

          -  Unstable medical condition