Effects of Oxytocin on Negative Symptoms and Social Cognition in Schizophrenia and Its Possible Mechanisms

Effects of Oxytocin on Negative Symptoms and Social Cognition in Schizophrenia and Its Behavioral Mechanisms

The purpose of this study was to investigate the effects of oxytocin on negative symptoms and social cognitive task performance in schizophrenia. The investigators conducted a randomized, placebo-controlled trial testing the effects of twice daily intranasal oxytocin treatment for 14 days on psychotic symptoms and social cognition in patients with schizophrenia. The investigators hypothesize that PANSS scores will decline significantly and several social cognition measures will improved significantly or nearly significantly in oxytocin but not placebo recipients.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: Oxytocin; Drug: Saline

Detailed Description

Social impairment is a primary cause of disability in schizophrenia, responds poorly to current antipsychotic medications and is related to deficits in social cognitive abilities, which include Theory of Mind, emotion recognition and attributional style. Oxytocin (OT) has many pro-social effects in animals and antipsychotic-like efficacy in preclinical tests. In this study, the investigators conducted a randomized, placebo-controlled trial testing the effects of twice daily intranasal oxytocin treatment for 14 days on psychotic symptoms and social cognition in patients with schizophrenia. The investigators will recruit patients with schizophrenia, screening of subjects included a review of psychiatric and medical history, physical examination, baseline social cognition measures were obtained followed by psychiatric ratings. Daily intranasal treatments were initiated after baseline assessments. Social cognition measures and psychiatric ratings were repeated beginning 50 min after the morning dose of study medication on treatment day 14. psychiatric ratings include The Positive and Negative Syndrome Scale (PANSS) and The Clinical Assessment Interview for Negative Symptoms (CAINS). The social cognition instruments are some social scales such as Toronto Alexithymia Scale, the Interpersonal Reactivity Index(IRI), and some computer tests such as reinforcement learning task and facial emotion identification test.

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200030
      • Shanghai Mental Health Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion criteria were:

1. aged between 18 and 55 years;
2. DSM-IV diagnosis of schizophrenia, acute schizophreniform disorder, or schizoaffective disorder.

Exclusion criteria were:

1. presence of other psychiatric diagnoses (e.g., depression);
2. active misuse of substance or alcohol;
3. intellectual disability (IQ < 70);
4. a history of neurological disorder.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: schizophrenia with oxytocin; Participants self-administered the oxytocin twice daily via intranasal route: before breakfast and before dinner. Each dose consists of six 0.1 ml insufflations (alternating between the left and right nostril) of oxytocin spray containing approximately 24 international units of oxytocin.	Drug: Oxytocin; It's a two-week treatment trial.Subjects self-administer intranasal study drug twice daily; before breakfast and before dinner. Each dose consists of six 0.1 ml insufflations (alternating between the left and right nostril) of OT spray containing approximately 24 international units of OT
PLACEBO_COMPARATOR: schizophrenia with Placebo; Participants self-administered the placebo twice daily via intranasal route: before breakfast and before dinner. Each dose consists of six 0.1 ml insufflations (alternating between the left and right nostril) of oxytocin spray containing approximately 24 international units of placebo.	Drug: Saline; It's a two-week treatment trial. Subjects self-administer intranasal study drug twice daily; before breakfast and before dinner. Each dose consists of six 0.1 ml insufflations (alternating between the left and right nostril) of saline spray containing approximately 24 international units of saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Positive and Negative Syndrome Scale (PANSS)	The Positive and Negative Syndrome Scale (PANSS) is a 30-items, 7-point rating scale, the 7 rating points represent increasing levels of psychopathology, 7 were chosen to constitute Positive Scale, 7 items for Negative Scale and the remaining 16 items for a General Psychopathology Scale. The scale scores range from 30 to 210, with higher scores indicating more severe psychotic symptoms.	baseline
The Positive and Negative Syndrome Scale (PANSS)	The Positive and Negative Syndrome Scale (PANSS) is a 30-items, 7-point rating scale, the 7 rating points represent increasing levels of psychopathology, 7 were chosen to constitute Positive Scale, 7 items for Negative Scale and the remaining 16 items for a General Psychopathology Scale. The scale scores range from 30 to 210, with higher scores indicating more severe psychotic symptoms.	the two-week endpoint
The Clinical Assessment Interview for Negative Symptoms (CAINS)	The Clinical Assessment Interview for Negative Symptoms (CAINS) is used to assess negative symptoms, the CAINS is a 13-item interview-based assessment comprising a nine-item "motivation and pleasure" factor (items included recreation, social and vocational expected pleasure and motivation), and a four-item "expression" factor (items included vocal prosody, gestures, facial, and speech). All items were scored on a five-point scale from 0 (no impairment) to 4 (severe deficit).The scale scores range from 0 to 52, with higher scores indicating more severe negative symptoms.	baseline
The Clinical Assessment Interview for Negative Symptoms (CAINS)	The Clinical Assessment Interview for Negative Symptoms (CAINS) is used to assess negative symptoms, the CAINS is a 13-item interview-based assessment comprising a nine-item "motivation and pleasure" factor (items included recreation, social and vocational expected pleasure and motivation), and a four-item "expression" factor (items included vocal prosody, gestures, facial, and speech). All items were scored on a five-point scale from 0 (no impairment) to 4 (severe deficit).The scale scores range from 0 to 52, with higher scores indicating more severe negative symptoms.	the two-week endpoint

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reinforcement Learning Task	The Gain versus Loss-Avoidance (GLA) task is a probabilistic reinforcement learning paradigm involving stimulus pairs in which choices resulted in reward or in loss avoidance.	baseline
Reinforcement Learning Task	The Gain versus Loss-Avoidance (GLA) task is a probabilistic reinforcement learning paradigm involving stimulus pairs in which choices resulted in reward or in loss avoidance.	the two-week endpoint
The Temporal Experience of Pleasure Scale (TEPS)	The Chinese version of the TEPS contains 20 items, using a 6-point Likert scale (from 1 = very false for me to 6 = very true for me), and measures anticipatory pleasure and consummatory pleasure, with higher scores indicating better pleasure experience.	baseline
The Temporal Experience of Pleasure Scale (TEPS)	The Chinese version of the TEPS contains 20 items, using a 6-point Likert scale (from 1 = very false for me to 6 = very true for me), and measures anticipatory pleasure and consummatory pleasure, with higher scores indicating better pleasure experience.	the two-week endpoint
Interpersonal Reactivity Index (IRI)	The Interpersonal Reactivity Index (IRI) (Davis, 1983) measures participants' empathic tendencies, it is a 28-item self-report scale measuring empathy and consists of four subscales: perspective taking, fantasy, personal distress, and empathic concern. While the first two subscales index, cognitive empathy, the last two subscales index affective empathy, each item is rated on a 5-point Likert scale ranging from 0 (does not describe me well) to 4 (describes me very well), and higher scores on the IRI-PT and the IRI-EC reflect greater cognitive and emotional empathy, respectively. In the Chinese version of the IRI, 6 items were deleted and 22 items remained (Chan, 1986) and it has been reported to have good reliability and validity in both normal and schizophrenic populations.	baseline
Interpersonal Reactivity Index (IRI)	The Interpersonal Reactivity Index (IRI) (Davis, 1983) measures participants' empathic tendencies, it is a 28-item self-report scale measuring empathy and consists of four subscales: perspective taking, fantasy, personal distress, and empathic concern. While the first two subscales index, cognitive empathy, the last two subscales index affective empathy, each item is rated on a 5-point Likert scale ranging from 0 (does not describe me well) to 4 (describes me very well), and higher scores on the IRI-PT and the IRI-EC reflect greater cognitive and emotional empathy, respectively. In the Chinese version of the IRI, 6 items were deleted and 22 items remained (Chan, 1986) and it has been reported to have good reliability and validity in both normal and schizophrenic populations.	the two-week endpoint
Toronto Alexithymia Scale (TAS)	The Toronto Alexithymia Scale (TAS-20) is used to assess the severity of alexithymia, it is a 20-item self-report instrument rated on a 5-point Liker-type scale ranging from 1 (strongly disagree) to 5 (strongly agree). Total scores range from 20 to 100, with higher scores indicating higher level of alexithymia. The TAS-20 consist of 3 factors: difficulty identifying feelings (DIF); difficulty describing feelings (DDF); externally oriented cognitive style of thinking (EOT). The Chinese version has been shown with having the same factor structure of the original version and has been associated with good internal consistency [15], which was adopted in this study.	baseline
Toronto Alexithymia Scale (TAS)	The Toronto Alexithymia Scale (TAS-20) is used to assess the severity of alexithymia, it is a 20-item self-report instrument rated on a 5-point Liker-type scale ranging from 1 (strongly disagree) to 5 (strongly agree). Total scores range from 20 to 100, with higher scores indicating higher level of alexithymia. The TAS-20 consist of 3 factors: difficulty identifying feelings (DIF); difficulty describing feelings (DDF); externally oriented cognitive style of thinking (EOT). The Chinese version has been shown with having the same factor structure of the original version and has been associated with good internal consistency [15], which was adopted in this study.	the two-week endpoint
emotion recognition task	The facial emotion identification test is used to assess facial emotion identification abilities, in which participants viewed 91 digital pictures of faces selected from the Japanese Female Facial Expression (JAFFE) Database (1998) and were asked to judge which emotion that particular face displayed on the screen was expressing (happy, sad, angry, afraid, surprise, disgusted or neutral).	baseline
emotion recognition task	The facial emotion identification test is used to assess facial emotion identification abilities, in which participants viewed 91 digital pictures of faces selected from the Japanese Female Facial Expression (JAFFE) Database (1998) and were asked to judge which emotion that particular face displayed on the screen was expressing (happy, sad, angry, afraid, surprise, disgusted or neutral).	the two-week endpoint

Collaborators and Investigators

• Sponsor: Shanghai Mental Health Center
• Collaborators: Chinese Academy of Sciences
• Investigators: Principal Investigator: Zhenghui Yi, Ph.D, Shanghai Mental Health Center

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 21, 2018
• Primary Completion (ACTUAL): March 31, 2020
• Study Completion (ACTUAL): March 31, 2020

Study Registration Dates

• First Submitted: June 27, 2018
• First Submitted That Met QC Criteria: September 5, 2018
• First Posted (ACTUAL): September 7, 2018

Study Record Updates

• Last Update Posted (ACTUAL): September 29, 2021
• Last Update Submitted That Met QC Criteria: September 23, 2021
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: schizophrenia; oxytocin; negative symptoms
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Reproductive Control Agents; Oxytocics; Oxytocin
• Other Study ID Numbers: KLMH2018K02

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No