A Pharmaco-imaging Approach to Predicting Social Functioning and Clinical Responses to Oxytocin Administration in Schizophrenia

Study Overview
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Brief Summary
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Schizophrenia has a devastating and disproportionate effect on veterans compared to the general US population. Some of the most disabling symptoms, such as low motivation, difficulty expressing emotions, and decreased ability to infer the mental states of others, cause poor social functioning. This means that veterans with schizophrenia have trouble navigating interpersonal interactions and building meaningful relationships in the community. Unfortunately, current antipsychotic medications typically only improve positive symptoms but fail to improve social functioning deficits, which are strong predictors of poor quality of life and functional outcomes. Oxytocin, a peptide found in the brain, plays an important role in social behavior and is known to moderate affiliation, stress, and learning across taxa. In this study, the investigators will test whether oxytocin could be an effective treatment for social functioning deficits in schizophrenia. The investigators will examine changes in brain activation to understand how oxytocin affects behavior and to predict which individuals may benefit from oxytocin treatment.

Detailed Description
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The study uses a combined within- and between-subject placebo-controlled study design. After screening, participants will be randomized into two study arms for the fMRI phase of the study. In each study arm, participants will complete a placebo-controlled, within-subject, pharmaco-fMRI paradigm with one of two possible dosages of oxytocin (20 or 40IU) and placebo. In the fMRI scanner, they will complete two well-validated theory of mind tasks: the false belief task and the person description task. Following the fMRI phase of the study, participants will be randomized to receive the same dosage of oxytocin the participant received in the fMRI phase, or placebo, twice daily for 3 weeks. Before and after the three weeks of drug administration, participants will be assessed for social functioning, social ability, negative symptoms, and theory of mind. More participants will be randomized to receive chronically administered oxytocin than placebo to maximize the study's power to test the investigators' hypothesis that acute oxytocin-induced increases in right temporo-parietal junction activity will be positively correlated with improvements in social functioning (primary outcome), social ability, negative symptoms, and theory of mind over three weeks of oxytocin administration.

Official Title
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A Pharmaco-imaging Approach to Predicting Social Functioning and Clinical Responses to Oxytocin Administration in Schizophrenia

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: Oxytocin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Veteran age 18-70 a diagnosis of schizophrenia, schizophreniform, schizoaffective, or brief psychotic disorder determined by the Structured Clinical Interview for DSM-5 no medication changes or psychiatric hospitalizations in the past month SFS modified raw score of no more than 75 Exclusion Criteria: substance use disorder in the past month, except mild to moderate cannabis use disorder illness affecting the nasal passages significant neurological/medical disorder pacemakers extensive dental work claustrophobia deafness inability to read currently participating in a psychosocial intervention targeting social functioning deficits currently taking high dose testosterone or estrogen/progesterone inability to complete VOT

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: The study uses a combined within- and between-subject placebo-controlled study design. After screening, participants will be randomized into two study arms for the fMRI phase of the study. In each study arm, participants will complete a placebo-controlled, within-subject, pharmaco fMRI paradigm with one of two possible dosages of oxytocin (20 or 40IU) and placebo. 75 participants will be randomized to receive 20IU oxytocin and placebo and 75 will be randomized to receive 40IU oxytocin and placebo, with the order of administration randomized and separated by two weeks. Following the fMRI phase of the study, participants will be randomized to receive the same dosage of oxytocin the participant received in the fMRI phase, or placebo, twice daily for 3 weeks.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intranasal Oxytocin<br>Dosages of oxytocin: 20IU or 40IU. | Drug: Oxytocin<br>* Intranasal administration of oxytocin<br>* Other names: Syntocinon;|
| Placebo Comparator: Placebo<br>Saline | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Social Functioning Score | The Social Functioning Scale is a 79-item semi-structured interview based assessment that includes [a global summary score (primary outcome) as well as seven subscales (secondary outcomes): social engagement, interpersonal communication, independence, competence, recreation, prosocial, and employment.] A mean of the subscale scores provides overall score of social functioning. Each subscale score is transformed into a standard distribution with a mean of 100 and standard deviation of 15 for comparability and interpretation. Higher scores indicates a high level of functioning. | From the baseline visit in the chronic OT administration portion of the study design to after three weeks of oxytocin administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CAINS Score (clinical assessment interview for negative symptoms) | Negative symptoms will be assessed with the CAINS, comprising two subscales reflecting the negative symptom factors: The 9-item Motivation and Pleasure subscale (each item is scored from 0 no impairments to 4 severe deficit) captures experiential negative symptoms by assessing motivation, behavior, and pleasure derived from social, vocational, and recreational activities over the past week. The MAP total score therefore ranges from 0-36. The 4-item Expression subscale (each item is scored from 0 no impairment to 4 severe deficit) captures both non-verbal (face, posture) and verbal expressivity (output, prosody). The EXP total score ranges from 0 to 16 (higher scores indicate greater severity of symptoms). The CAINS has excellent convergent and divergent validity. | From the baseline visit in the chronic OT administration portion of the study design to after three weeks of oxytocin administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Oxytocin