Oxytocin and CBSST for People With Schizophrenia
Condition: Schizophrenia; Schizoaffective Disorder
MeSH terms: Schizophrenia; Psychotic Disorders
Study type: Interventional

Summary: 
      A significant proportion of people with schizophrenia are characterized by impaired ability
      to socially engage with others, which may reflect social aversion secondary to defeatist
      beliefs; decreased motivation for social interactions; and/or impairment in the normal
      reinforcement value of social interactions. These impairments in social function have been
      shown to be associated with social skill deficits; and decreased ability to identify and
      remember emotional facial expressions and empathize with the emotional status of others.
      Unfortunately, pharmacological interventions have limited benefits for impaired social
      function, whereas psychosocial interventions provide only partial benefit for this critical
      aspect of the illness. The development of an effective intervention for functional outcomes
      remains a central therapeutic challenge. Cognitive Behavioral Social Skills Training (CBSST)
      uses corrective feedback and reinforcement provided by successful interactions to challenge
      and reduce defeatist performance beliefs that contribute to low drive and interfere with
      social functioning. CBSST has been shown to have modest effects on social function in people
      with schizophrenia. Oxytocin plays a critical role in the regulation of normal social
      affiliative behavior; it is hypothesized to enhance social affiliation through the reduction
      of anxiety or social risk aversion; the enhancement of motivation for prosocial approach
      behavior; and/or increased modulation of the salience and processing of social cues. People
      with schizophrenia have decreased oxytocin levels, which are associated with an impaired
      ability to identify facial emotions and decreased prosocial behaviors. The study will be
      comprised of three phases: 1) 2-week Evaluation Phase; 2) 24-week Double-blind Treatment
      Phase; and 3) 3-month Follow-up Phase.
    

Detailed description: 
      A NIMH mission priority is the development of new and better interventions, whose focus
      extends beyond symptom amelioration to the development of interventions that allow people who
      suffer from severe mental illnesses "to live full and productive lives" (NIMH Strategic Plan,
      2008). In particular, the NIMH Strategic Plan notes the importance of translating "research
      on the biological causes of disorder to inform and develop psychosocial and biomedical
      interventions that target core features of disease, assess outcomes appropriate to the course
      of illness under study, and develop study designs that have impact on these features." The
      current proposal is built upon the observations that: 1) people with schizophrenia are
      characterized by marked impairments in their social function; 2) current pharmacological
      treatments do not address these impairments; 3) CBSST has been shown to have modest effects
      on social function in people with schizophrenia. This limited efficacy may be related to the
      lack of interest or drive people with schizophrenia have for social interactions; 4) oxytocin
      plays a critical role in normal social affiliative behavior through a) the reduction of
      anxiety or social risk aversion, b) the enhancement of motivation for prosocial approach or
      affiliative behavior, and/or c) increased modulation of the salience and processing of social
      cues; and 5) decreased oxytocin is associated with social function impairments in people with
      schizophrenia.

      The proposed study is based on the proposition that the use of a pharmacological agent, whose
      behavioral effects compliment the psychological mechanisms of action of a psychosocial
      intervention, is an important adaptation of an intervention previously shown to have moderate
      effects on social function. The addition of oxytocin to CBSST is hypothesized to: 1) enhance
      the reduction of defeatist performance beliefs by reducing social risk aversiveness and
      avoidance, which would increase exposure to reinforcement and corrective feedback; 2) enhance
      social skill acquisition through improvement of proximal social behaviors, e.g. making eye
      contact and attending to the facial expressions of social partners; and 3) facilitate the
      translation of learned social skills into community practice through its effects on prosocial
      attachment behaviors, reduction in social disinterest, and effects on distal behaviors, e.g.
      initiating conversations and responding to social invitations. Increased social risk taking
      within and between sessions would expose participants to a greater frequency of positive
      feedback and success experiences, which would provide evidence to dispute their defeatist
      beliefs and social disinterest attitudes. In addition, increased social risk taking could
      improve homework adherence (e.g., practicing talking to people in the community) and
      engagement in new community activities. These interactive effects would subsequently lead to
      a substantial improvement in CBSST efficacy for social function. Ultimately, the importance
      of improved social function is the effect that such improvement would have on overall levels
      of health and functioning, including vocational outcome.

      The proposed study will enable us to collect preliminary data on the acceptability, efficacy,
      feasibility, and safety of the proposed intervention. In particular, this would be the first
      study to examine the safety of long-term oxytocin in this population. The study will also
      provide critical data on the feasibility of recruiting and retaining participants with
      schizophrenia in a long-term intervention, which combines two different therapeutic
      modalities: CBSST and oxytocin. If found to be efficacious, feasible, and well-tolerated, we
      will plan to conduct a larger study, which would include the use of cognitive and imaging
      biomarkers, to more fully elucidate the mechanism of action of the observed treatment
      effects. The investigators will address the following specific aims:

      Aim #1 (Efficacy): To determine if CBSST + oxytocin compared to CBSST + placebo-oxytocin is
      associated with improved social function.

      Aim #2 (Safety): To determine if CBSST + oxytocin compared to CBSST + placebo-oxytocin is
      associated with increased incidence of side effects.

      Aim #3 (Change Mechanism): To determine if CBSST + oxytocin compared to CBSST +
      placebo-oxytocin is associated with reduced social aversion, including social disinterest and
      defeatist performance beliefs; increased ability to trust others; and/or improved performance
      on facial recognition and memory measures.

      Aim #4 (Other Outcomes): To determine if CBSST + oxytocin compared to CBSST +
      placebo-oxytocin is associated with improved neuropsychological test performance, and/or
      decreased positive, negative, and/or anxiety/depression symptoms, and clinical global
      improvement.
    

Intervention name(s): CBSST + Oxytocin; CBSST + Placebo
Intervention type(s): Drug; Drug
Intervention description(s): The oxytocin dose of 80 IU/day, will be administered in two divided doses: 40 IU in the morning and 40 IU in the evening. Oxytocin will be administered intranasally (10 puffs of the spray, 5 in each nostril at each administration). CBSST groups will occur for an hour twice/week. Nasal spray will be administered an hour prior to the CBSST group.; Matching placebo spray will be administered intranasally (10 puffs of the spray, 5 in each nostril at each administration). CBSST groups will occur for an hour twice/week. Nasal spray will be administered an hour prior to the CBSST group.
Other intervention name(s): sugar pill
Intervention MeSH terms: Oxytocin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Oxytocin; Social function; CBSST