Oxytocin and CBSST for People With Schizophrenia
| Status: | Completed |
|---|---|
| Conditions: | Schizophrenia, Psychiatric |
| Therapuetic Areas: | Psychiatry / Psychology |
| Healthy: | No |
| Age Range: | 18 - 55 |
| Updated: | 2/9/2018 |
| Start Date: | January 2014 |
| End Date: | August 2016 |
Combined Oxytocin and CBSST for Social Function in People With Schizophrenia
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.
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.
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.
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.
Inclusion Criteria:
1. DSM-IV-TR diagnosis of schizophrenia or schizoaffective disorder
2. Scale for the Assessment of Negative Symptoms asociality item score ≥ 2
3. Considered clinically stable by the treating psychiatrist
4. Stable treatment with the same antipsychotic for at least 60 days and the same dose
for at least the 30 days prior to study entry.
5. Male or female of any race.
Exclusion Criteria:
1. Organic brain disorder, including cerebrovascular accident; epilepsy; traumatic brain
injury, loss of consciousness (LOC) for more than 30 minutes
2. Mental retardation
3. Medical conditions, whose pathology or treatment could alter the presentation or
treatment of schizophrenia or significantly increase the risk associated with the
proposed treatment protocol
4. Participant is pregnant or is lactating
5. History of chronic allergic rhinitis
6. DSM-IV-TR diagnosis of alcohol or substance dependence (except nicotine) within the
last 6 months, or participant has met dependence criteria for 5 years or more.
7. DSM-IV-TR diagnosis of alcohol or substance abuse (except nicotine) within the last
month
8. Participant has a past history of polydypsic hyponatremia (defined by sodium levels
below 130 mmol/L) or has a current sodium level below 135 mmol/L
9. Participant with EKG evidence of any of the following cardiac arrhythmias: QTc
prolongation (Males: 450 msec or greater; females: 470 msec or greater); atrial
fibrillation; ventricular or supraventricular tachycardia; and 2nd or 3rd degree A-V
Block
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