Does Acute Oxytocin Administration Enhance Social Cognition in Individuals With Schizophrenia?

NCT ID: NCT01312272

Last Updated: 2014-05-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-04-30
• Study Completion Date: 2012-08-31

Brief Summary

Individuals with schizophrenia have been found to have deficits in social cognition, which is defined as the functions that are engaged during social interactions. Social cognition has been found to be critical in predicting multiple aspects of community functioning. There are no currently available medications that have been consistently found to improve social cognition in individuals with schizophrenia. Oxytocin functions as a neurotransmitter that is thought to be involved in multiple aspects of social behavior and related emotions. In this study, we test the hypothesis that acute administration of intranasal oxytocin will improve social cognition in individuals with schizophrenia.

Detailed Description

Schizophrenia is characterized by the presence of positive symptoms (delusions, hallucinations, disorganization of thought process and behavior) as well as negative symptoms (blunted affect, alogia, and avolition), neurocognitive deficits, and impaired social cognition. While positive symptoms can often respond well to antipsychotic medications, the latter symptoms are more difficult to treat. In this study, we will focus on social cognition, which is defined as the functions that are engaged during social interactions. Social cognition has been categorized into four main domains: theory of mind, social perception, attributional bias, and emotional processing. Social cognition in patients with schizophrenia has been found to be critical in predicting multiple aspects of community functioning. There are currently two broad approaches to improve social cognition in patients with schizophrenia: pharmacological and psychosocial interventions. While psychosocial interventions (training exercises to target improvement in domains of social cognition) have shown some benefit, their resultant improvements have been limited in their distribution across multiple domains as well as their generalization to improved functioning in the community. Pharmacological trials have yielded mixed results, and there are not any currently available medications that have been consistently found to improve social cognition in patients with schizophrenia2. One potential future therapeutic target for enhancing social cognition is the oxytocin system.

Oxytocin is a nine-amino acid peptide that, in addition to its role in the periphery for regulating lactation and uterine contractions, functions centrally as a neurotransmitter which is involved in multiple aspects of social behavior and related emotions. Specifically, it has been found to modulate emotion recognition, trust, eye contact, empathic accuracy, as well as envy and gloating. Given oxytocin's role in social functioning, in conjunction with the deficits in social functioning found frequently in individuals with schizophrenia, there have been several studies over the past three decades examining the oxytocin system in humans with schizophrenia and in rodent experimental models.

It has been found that individuals with schizophrenia do not show the same level of increase in oxytocin as normal controls in response to trust-related interpersonal interactions, and low plasma oxytocin predicted negative symptoms of schizophrenia. Additionally, it has also been found that plasma oxytocin levels predicted the ability of patients with schizophrenia to identify facial expressions. Finally, it has been found recently that sustained regular administration of intranasal oxytocin significantly reduced both positive and negative symptoms of schizophrenia. Thus, there is significant evidence supporting further research studying the effect of oxytocin on social cognition. It is not yet known if exogenous administration of oxytocin will have acute effects on neuropsychological measures of social cognition in individuals with schizophrenia, and this is the focus of this proposed pilot study.

The overall hypothesis guiding this study is that acute oxytocin administration will improve social cognition (as assessed by a composite score comprising two measures of "low level" social cognitive processes and two measures of "high level" social cognitive processes) in individuals with schizophrenia. Our primary goals are to assess the feasibility of this experimental paradigm and to generate pilot data and obtain estimates of effect sizes which can be used in planning future larger studies.

Conditions

Schizophrenia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Inactive nasal spray

A placebo nasal spray will be prepared to be otherwise identical to the active treatment nasal spray except lacking oxytocin. The ingredients in the inactive nasal spray are mannitol, glycerin, and preserved water.

Group Type: PLACEBO_COMPARATOR

Inactive placebo nasal spray

Intervention Type: DRUG

A placebo nasal spray will be prepared identically to the oxytocin nasal spray except lacking oxytocin. Its ingredients are mannitol, glycerin, and preserved water. It will be administered at 5 sprays to each nostril, one time.

Intranasal Oxytocin

Oxytocin nasal spray (40 units/ml) will be administered in a single intranasal dose of 40 IU. Its formula is: oxytocin 1 unit/mg mannitol trituration 0.2Gm + glycerin USP 0.1ml + preserved water 5ml.

Group Type: EXPERIMENTAL

Oxytocin

Intervention Type: DRUG

Oxytocin 40 units/ml nasal spray: use 5 sprays per nostril (40 IU total) one time

Interventions

Oxytocin

Oxytocin 40 units/ml nasal spray: use 5 sprays per nostril (40 IU total) one time

Intervention Type: DRUG

Inactive placebo nasal spray

A placebo nasal spray will be prepared identically to the oxytocin nasal spray except lacking oxytocin. Its ingredients are mannitol, glycerin, and preserved water. It will be administered at 5 sprays to each nostril, one time.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Veteran being treated in the Veterans Administration Healthcare System
• Meet DSM-IV-TR criteria for Schizophrenia
• At least 6 months since any hospitalization or substantial increase in level of care for an acute exacerbation of psychotic symptoms
• At least 1 month since meeting the criteria for having a major depressive episode
• At least 6 months since any behaviors suggesting any potential danger to self or others
• Adherence to the regular administration of an antipsychotic medication (e.g., risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole, paliperidone, iloperidone, asenapine, fluphenazine, haloperidol, loxapine, molindone, perphenazine, thiothixene, chlorpromazine, clozapine)
• Dose of antipsychotic medication not varying by more than 25% over the 3 months prior to study participation
• No acute medical problems
• Chronic medical conditions (e.g., hypertension, diabetes, dyslipidemia) consistently treated and stable for at least 3 months prior to study participation
• Ability to provide signed informed consent and to cooperate with study procedures

Exclusion Criteria

• Documented history of mental retardation or severe learning disability
• History of treatment with electroconvulsive therapy within 6 months prior to study participation
• History of neurological or neuropsychiatric condition (e.g., stroke, severe traumatic brain injury, epilepsy, etc.)
• Documented history of persistent substance abuse or dependence within 6 months prior to study participation
• History of hyponatremia within the past 6 months
• Allergic rhinitis or other inflammation of the nasal mucosa

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

VA Greater Los Angeles Healthcare System

FED

Sponsor Role: lead

Responsible Party

Michael C. Davis, M.D., Ph.D.

Fellow / Physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Stephen R Marder, M.D.

Role: PRINCIPAL_INVESTIGATOR

VA Greater Los Angeles

Locations

West Los Angeles VA Healthcare Center

Los Angeles, California, United States

Countries

United States

References

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Reference Type: BACKGROUND

PMID: 20855907 (View on PubMed)

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Reference Type: BACKGROUND

PMID: 15931222 (View on PubMed)

Shamay-Tsoory SG, Fischer M, Dvash J, Harari H, Perach-Bloom N, Levkovitz Y. Intranasal administration of oxytocin increases envy and schadenfreude (gloating). Biol Psychiatry. 2009 Nov 1;66(9):864-70. doi: 10.1016/j.biopsych.2009.06.009. Epub 2009 Jul 29.

Reference Type: BACKGROUND

PMID: 19640508 (View on PubMed)

Webber MA, Marder SR. Better pharmacotherapy for schizophrenia: what does the future hold? Curr Psychiatry Rep. 2008 Aug;10(4):352-8. doi: 10.1007/s11920-008-0056-8.

Reference Type: BACKGROUND

PMID: 18627675 (View on PubMed)

Davis MC, Lee J, Horan WP, Clarke AD, McGee MR, Green MF, Marder SR. Effects of single dose intranasal oxytocin on social cognition in schizophrenia. Schizophr Res. 2013 Jul;147(2-3):393-7. doi: 10.1016/j.schres.2013.04.023. Epub 2013 May 12.

Reference Type: RESULT

PMID: 23676253 (View on PubMed)

Related Links

http://www.ncbi.nlm.nih.gov/pubmed/23676253

Link to PubMed journal article citation for peer-reviewed publication describing study

Other Identifiers

PCC 2011-020223

Identifier Type: -

Identifier Source: org_study_id