Oxytocin and Social Cognition in Schizophrenia

Objective: Social Cognition and Emotional Intelligence have been shown to be deficient in patients with schizophrenia and these are not remediated by antipsychotic medications or psychosocial interventions. Social cognition is associated with functional outcome, an important step in striving for recovery in this population. The hormone and neurotransmitter, oxytocin, which has been associated with social bonding and trust has been shown to improve measures of some aspects of social cognition in humans. The study will assess the effect of acute administration of intranasal oxytocin on measures of social cognition and functioning as well as on emotional intelligence and symptoms.

Study population: The study population will include patients with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder who have been on a stable medication regimen for 6 weeks. We will enroll a total of 30 subjects (N=15 placebo and N=15 oxytocin groups).

Experimental design and methods: After a one week lead in phase, participants will undergo 3 weeks of oxytocin (20 IU BID) or placebo administration (double blind) in addition to their existing medication regimen. Outcome measures will be administered during the lead in phase, and at the end of the study drug administration phase (under the acute effect of OT). The primary outcome measure will be the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) and the Maryland Assessment of Social Competence (MASC). Secondary measures include rating from the domains of social cognition (emotion perception, attributional style, theory of mind and social perception), symptom rating and measures of social anxiety and quality of life. Side effects and symptoms will be measured weekly.

Study Overview

• Status: Completed
• Conditions: Social Anxiety; Social Cognition; Emotional Intelligence
• Intervention / Treatment: Drug: Oxytocin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Catonsville, Maryland, United States, 21228
      • Maryland Psychiatric Research Center (MPRC) Outpatient Research Program (ORP); the MPRC Treatment Research Program (TRP)

Participation Criteria

Eligibility Criteria

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

Description

Inclusion criteria:

All participants must:

1. Be between age 18 and 55.
2. Meet DSM-IV criteria for Schizophrenia or Schizoaffective Disorder.
3. Treated with a stabilized antipsychotic regimen (i.e., have had no change in antipsychotic medication in the previous six weeks and no change in dose for the past 30 days).

Exclusion criteria:

Participants will be excluded if they have evidence of:

1. DSM-IV criteria for substance dependence in the last 6 months or DSM-IV criteria for abuse in the past 30 days.
2. Cognitive impairment severe enough to preclude informed consent or valid responses on questionnaires. This is defined an as a score of less than 10 on the Evaluation to Sign Consent (ESC) and judged by the treating clinician.
3. Medical illness that in the view of the investigators would compromise participation in research.
4. History of polydipsia and/or hyponatremia
5. Clinically significant endocrine disorders, as judged by the PI. Abnormalities in prolactin levels and thyroid function tests associated with the use of dopamine antagonist medications will not be exclusionary.

6. Pregnancy, planning to become pregnant, or breastfeeding. In addition, women of childbearing age are required to use an effective form of birth control for the duration of the study. Effective forms of birth control include:

   • hormonal contraceptives (birth control pills, injectable hormones, vaginal ring hormones),
   • surgical sterility (tubal ligation or hysterectomy)
   • IUD
   • Diaphragm with spermicide
   • Condom with spermicide
   • Abstinence
7. Use of any drugs (prostaglandins, vasoconstricting agents or anesthetic medications, for example) that may interact with oxytocin. Justification: Avoidance of adverse interaction with oxytocin. Assessment tool(s): Clinical interview and toxicology screen
8. History of hypersensitivity to oxytocin or vehicle, i.e. propyl parahydroxybenzoate, methyl parahydroxybenzoate, chlorobutanol hemihydrate. Assessment tool: clinical interview
9. Presence of or history of clinically significant allergic rhinitis as assessed by the PI, M.D., or Nurse. Justification: Inflammation of nasal mucosa could interfere with mucosal absorption of intranasally administered OT. Current rhinitis from an upper respiratory infection should be resolved prior to enrollment in study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oxytocin; We will purchase OT from PharmaWorld, an international pharmacy located in Switzerland; the preparation of intranasal OT is manufactured by Novartis and sold under the trade name: Syntocinon. We have obtained an IND (number 78,246) for Syntocinon (intranasal oxytocin) manufactured by Novartis.	Drug: Oxytocin; Oxytocin given as 20 IU BID
Placebo Comparator: Placebo; We will be purchasing oxytocin placebo nasal spray through LABOSWISS located in Davos, Switzerland and distributed through PharmaWorld. LABOSWISS will manufacture the matching the placebo under GDP guidelines. The placebo will be in every way identical to the oxytocin formulation but will not contain OT.	Drug: Placebo; Placebo given as 20 IU BID

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To Determine Whether Exogenous OT Enhances Emotional Intelligence and Improves Performance on Measures of Social Cognition for Schizophrenia or Schizoaffective Patients	Mayer-Salovay Caruso Emotional Intelligence Test (Mayer et al., 2002; MSCEIT) This is a self report instrument that consists of 141 items and 8 ability subscales, which assess four components (branches) of emotion processing: identifying emotions, using emotions, understanding emotions, and managing emotions. For this study we will focus on the managing emotions and understanding emotions components. There are 29 total items assessed with a total score ranging from 5-145. The higher the score the better the outcome.	participants are assessed at baseline and end point

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To Determine Whether OT Improves Measures of Social Anxiety.	To determine whether OT improves measures of social anxiety as measured by the Social Interaction Anxiety Scale. This assessment has 20 items scored 0-4 for a total minimum score of 0 and maximum score of 80. The lower the score the better the outcome.	Outcomes are compared between Baseline and endpoint

Collaborators and Investigators

• Sponsor: University of Maryland, Baltimore
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Deanna L Kelly, Pharm.D, BCPP, University of Maryland, College Park; Principal Investigator: Mary Lee, MD, National Institute on Drug Abuse (NIDA)

Publications and helpful links

General Publications

• Lee MR, Wehring HJ, McMahon RP, Linthicum J, Cascella N, Liu F, Bellack A, Buchanan RW, Strauss GP, Contoreggi C, Kelly DL. Effects of adjunctive intranasal oxytocin on olfactory identification and clinical symptoms in schizophrenia: results from a randomized double blind placebo controlled pilot study. Schizophr Res. 2013 Apr;145(1-3):110-5. doi: 10.1016/j.schres.2013.01.001. Epub 2013 Feb 13.

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Actual): January 1, 2012
• Study Completion (Actual): January 1, 2012

Study Registration Dates

• First Submitted: April 20, 2009
• First Submitted That Met QC Criteria: April 20, 2009
• First Posted (Estimate): April 21, 2009

Study Record Updates

• Last Update Posted (Actual): October 2, 2019
• Last Update Submitted That Met QC Criteria: September 25, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Schizophrenia; Oxytocin; Social Cognition
• 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: HP-00041024; P50MH082999 (U.S. NIH Grant/Contract)