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

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.