Social Safety Learning in the Brain Oxytocin System

The investigators are conducting this research study to examine whether oxytocin enhances social safety learning (learning safety through the experience of another individual) in people with social anxiety disorder (SAD) compared to healthy volunteers. Oxytocin is a hormone that can also act as a chemical messenger in the brain. Oxytocin plays a role in a number of functions, including responding to fear and social interactions. In this study, the investigators would like to compare the effects of oxytocin and placebo nasal sprays in adults with SAD and healthy adults. This research study will compare an oxytocin nasal spray to a placebo nasal spray. About 120 people will take part in this research study, all at the University of Washington (UW).

Study Overview

• Status: Completed
• Conditions: Social Phobia
• Intervention / Treatment: Drug: Oxytocin nasal spray or placebo

Detailed Description

The goal of the current study is to examine the potential role of oxytocin in enhancing social learning in SAD. The investigators' primary hypothesis is that vicarious extinction learning will contribute to safety learning and that oxytocin will potentiate vicarious extinction learning in patients with SAD, compared to healthy controls (HC). The investigators will directly test the effect of intranasal oxytocin and matching placebo on the brain mechanisms underlying vicarious extinction learning using a novel task. 60 adults with SAD and 60 healthy control participants will perform a task that involves three phases: (i) a standard social fear acquisition procedure while in a mock scanner, followed by (ii) a vicarious extinction and (iii) fear reinstatement test procedure, while being scanned during functional magnetic resonance imaging (fMRI). Participants will receive oxytocin or placebo prior to the extinction phase. The investigators will also measure skin conductance responses as an index of learning in each phase.

• Study Type: Interventional
• Enrollment (Actual): 121
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

For Clinical Sample

• Men and women age 18-45
• Women must be having regular menstrual cycles and not be taking oral contraception
• Primary diagnosis of social anxiety disorder

For Healthy Sample

• Men and women age 18-45
• Women must be having regular menstrual cycles and not be taking oral contraception
• No current or lifetime history of psychiatric, neurological, or medical disorders

Exclusion Criteria:

For All Groups

• Pregnancy or breastfeeding
• Positive urine drug screening test result
• History of nasal pathology
• Current use of any psychotropic medication or steroids
• Active substance use disorder within the past 6 months
• History of serious medical illnesses or untreated endocrine diseases
• History of head injury, neurological disorder, or neurosurgical procedure
• Positive magnetic resonance (MR) screen

For Clinical Sample

• Lifetime diagnoses of mania or psychotic disorder based on the Diagnostic and Statistical Manual (DSM- 5th ed)
• Acute suicidal ideation

For Healthy Sample

• Lifetime DSM-5 diagnosis of any medical, neurological, or psychiatric illness

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Clinical; This group consists of individuals with at least moderate symptoms of social anxiety disorder. This group will receive either an oxytocin or placebo administration (blind randomization).	Drug: Oxytocin nasal spray or placebo; Single acute administration of 24 international units (IU) oxytocin or matching placebo
Placebo Comparator: Controls; This group consists of a healthy sample of individuals (no lifetime diagnoses of mania or psychotic disorders). This group will receive either an oxytocin or placebo administration (blind randomization).	Drug: Oxytocin nasal spray or placebo; Single acute administration of 24 international units (IU) oxytocin or matching placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neural Responses in the CS+R vs CS+S Contrast in the Insula During the Extinction Phase	Change in task-related blood oxygen level dependent (BOLD) responses in the insula during vicarious extinction (specifically for CS+R (reinforced) versus CS+S (non-reinforced) conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the insula region of interest and estimated using a general linear model. Higher mean responses reflect greater discrimination (better able to distinguish between threat and safety cues) between the task conditions.	immediately (45 minutes) after receiving drug
Neural Responses in the CS+R vs CS+S Contrast in the Hippocampus During the Extinction Phase	Change in task-related blood oxygen level dependent (BOLD) responses in the hippocampus during vicarious extinction (specifically for CS+R (reinforced) versus CS+S (non-reinforced) conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the hippocampus region of interest and estimated using a general linear model. Higher mean responses reflect greater discrimination (better able to distinguish between threat and safety cues) between the task conditions.	immediately (45 minutes) after receiving drug
Neural Responses in the CS+R vs CS+S Contrast in the Anterior Cingulate Cortex During the Extinction Phase	Change in task-related blood oxygen level dependent (BOLD) responses in the anterior cingulate cortex during vicarious extinction (specifically for CS+R (reinforced) versus CS+S (non-reinforced) conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the anterior cingulate cortex region of interest and estimated using a general linear model. Higher mean responses reflect greater discrimination (better able to distinguish between threat and safety cues) between the task conditions.	immediately (45 minutes) after receiving drug
Neural Responses in the CS+R vs CS+S Contrast in the Ventromedial Prefrontal Cortex During the Extinction Phase	Change in task-related blood oxygen level dependent (BOLD) responses in the ventromedial prefrontal cortex during vicarious extinction (specifically for CS+R (reinforced) versus CS+S (non-reinforced) conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the ventromedial prefrontal cortex region of interest and estimated using a general linear model. Higher mean responses reflect greater discrimination (better able to distinguish between threat and safety cues) between the task conditions.	immediately (45 minutes) after receiving drug
Neural Responses in the CS+R vs CS+S Contrast in the Anterior Cingulate Cortex During the Reinstatement Phase	Change in task-related blood oxygen level dependent (BOLD) responses in the anterior cingulate cortex during fear reinstatement, which tests for the return of fear (specifically for CS+R (reinforced) versus CS+S (non-reinforced) conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the anterior cingulate cortex region of interest and estimated using a general linear model. Higher mean responses reflect greater discrimination (better able to distinguish between threat and safety cues) between the task conditions.	immediately (45 minutes) after receiving drug
Neural Responses in the CS+R vs CS+S Contrast in the Insula During the Reinstatement Phase	Change in task-related blood oxygen level dependent (BOLD) responses in the insula during fear reinstatement, which tests for the return of fear (specifically for CS+R (reinforced) versus CS+S (non-reinforced) conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the insula region of interest and estimated using a general linear model. Higher mean responses reflect greater discrimination (better able to distinguish between threat and safety cues) between the task conditions.	immediately (45 minutes) after receiving drug
Neural Responses in the CS+R vs CS+S Contrast in the Hippocampus During the Reinstatement Phase	Change in task-related blood oxygen level dependent (BOLD) responses in the hippocampus during fear reinstatement, which tests for the return of fear (specifically for CS+R (reinforced) versus CS+S (non-reinforced) conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the hippocampus region of interest and estimated using a general linear model. Higher mean responses reflect greater discrimination (better able to distinguish between threat and safety cues) between the task conditions.	immediately (45 minutes) after receiving drug
Neural Responses in the CS+R vs CS+S Contrast in the Amygdala During the Reinstatement Phase	Change in task-related blood oxygen level dependent (BOLD) responses in the amygdala during fear reinstatement, which tests for the return of fear (specifically for CS+R (reinforced) versus CS+S (non-reinforced) conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the amygdala region of interest and estimated using a general linear model. Higher mean responses reflect greater discrimination (better able to distinguish between threat and safety cues) between the task conditions.	immediately (45 minutes) after receiving drug
Skin Conductance Responses (SCR) to CS- During Extinction	mean skin conductance responses (SCR) for CS- stimuli during Extinction	immediately (45 minutes) after receiving drug
Skin Conductance Responses (SCR) to CS+S During Extinction	mean skin conductance responses (SCR) for CS+S stimuli during Extinction	immediately (45 minutes) after receiving drug
Skin Conductance Responses (SCR) to CS+R During Extinction	mean skin conductance responses (SCR) for CS+R stimuli during Extinction	immediately (45 minutes) after receiving drug
Skin Conductance Responses (SCR) to CS- During Reinstatement	mean skin conductance responses (SCR) for CS- stimuli during Reinstatement	immediately (45 minutes) after receiving drug
Skin Conductance Responses (SCR) to CS+S During Reinstatement	mean skin conductance responses (SCR) for CS+S stimuli during Reinstatement	immediately (45 minutes) after receiving drug
Skin Conductance Responses (SCR) to CS+R During Reinstatement	mean skin conductance responses (SCR) for CS+R stimuli during Reinstatement	immediately (45 minutes) after receiving drug
Neural Responses in the CS+R vs CS- Contrast in the Insula During the Extinction Phase	Change in task-related blood oxygen level dependent (BOLD) responses in the insula during vicarious extinction (specifically for CS+R (reinforced) versus CS+S (non-reinforced) conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the insula region of interest and estimated using a general linear model. Higher mean responses reflect greater discrimination (better able to distinguish between threat and safety cues) between the task conditions.	immediately (45 minutes) after receiving drug
Neural Responses in the CS+R vs CS- Contrast in the Amygdala During the Extinction Phase	Change in task-related blood oxygen level dependent (BOLD) responses in the amygdala during vicarious extinction (specifically for CS+R (reinforced) versus CS+S (non-reinforced) conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the amygdala region of interest and estimated using a general linear model. Higher mean responses reflect greater discrimination (better able to distinguish between threat and safety cues) between the task conditions.	immediately (45 minutes) after receiving drug
Neural Responses in the CS+R vs CS+S Contrast in the Ventromedial Prefrontal Cortex During the Reinstatement Phase	Change in task-related blood oxygen level dependent (BOLD) responses in the ventromedial prefrontal cortex during fear reinstatement, which tests for the return of fear (specifically for CS+R (reinforced) versus CS+S (non-reinforced) conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the ventromedial prefrontal region of interest and estimated using a general linear model. Higher mean responses reflect greater discrimination (better able to distinguish between threat and safety cues) between the task conditions.	immediately (45 minutes) after receiving drug
Neural Responses in the CS+R vs CS- Contrast in the Hippocampus During the Extinction Phase	Change in task-related blood oxygen level dependent (BOLD) responses in the hippocampus during vicarious extinction (specifically for CS+R (reinforced) versus CS+S (non-reinforced) conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the hippocampus region of interest and estimated using a general linear model. Higher mean responses reflect greater discrimination (better able to distinguish between threat and safety cues) between the task conditions.	immediately (45 minutes) after receiving drug
Neural Responses in the CS+R vs CS- Contrast in the Anterior Cingulate Cortex During the Extinction Phase	Change in task-related blood oxygen level dependent (BOLD) responses in the anterior cingulate cortex during vicarious extinction (specifically for CS+R (reinforced) versus CS+S (non-reinforced) conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the anterior cingulate cortex region of interest and estimated using a general linear model. Higher mean responses reflect greater discrimination (better able to distinguish between threat and safety cues) between the task conditions.	immediately (45 minutes) after receiving drug
Neural Responses in the CS+R vs CS- Contrast in the Ventromedial Prefrontal Cortex During the Extinction Phase	Change in task-related blood oxygen level dependent (BOLD) responses in the ventromedial prefrontal cortex during vicarious extinction (specifically for CS+R (reinforced) versus CS+S (non-reinforced) conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the ventromedial prefrontal cortex region of interest and estimated using a general linear model. Higher mean responses reflect greater discrimination (better able to distinguish between threat and safety cues) between the task conditions.	immediately (45 minutes) after receiving drug
Neural Responses in the CS+R vs CS- Contrast in the Amygdala During the Reinstatement Phase	Change in task-related blood oxygen level dependent (BOLD) responses in the amygdala during fear reinstatement, which tests for the return of fear (specifically for CS+R (reinforced) versus CS- (non-reinforced) conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the amygdala region of interest and estimated using a general linear model. Higher mean responses reflect greater discrimination (better able to distinguish between threat and safety cues) between the task conditions.	immediately (45 minutes) after receiving drug
Neural Responses in the CS+R vs CS- Contrast in the Insula During the Reinstatement Phase	Change in task-related blood oxygen level dependent (BOLD) responses in the insula during fear reinstatement, which tests for the return of fear (specifically for CS+R (reinforced) versus CS- (non-reinforced) conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the insula region of interest and estimated using a general linear model. Higher mean responses reflect greater discrimination (better able to distinguish between threat and safety cues) between the task conditions.	immediately (45 minutes) after receiving drug
Neural Responses in the CS+R vs CS- Contrast in the Hippocampus During the Reinstatement Phase	Change in task-related blood oxygen level dependent (BOLD) responses in the hippocampus during fear reinstatement, which tests for the return of fear (specifically for CS+R (reinforced) versus CS- (non-reinforced) conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the hippocampus region of interest and estimated using a general linear model. Higher mean responses reflect greater discrimination (better able to distinguish between threat and safety cues) between the task conditions.	immediately (45 minutes) after receiving drug
Neural Responses in the CS+R vs CS- Contrast in the Anterior Cingulate Cortex During the Reinstatement Phase	Change in task-related blood oxygen level dependent (BOLD) responses in the anterior cingulate cortex during fear reinstatement, which tests for the return of fear (specifically for CS+R (reinforced) versus CS- (non-reinforced) conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the anterior cingulate cortex region of interest and estimated using a general linear model. Higher mean responses reflect greater discrimination (better able to distinguish between threat and safety cues) between the task conditions.	immediately (45 minutes) after receiving drug
Neural Responses in the CS+S vs CS- Contrast in the Hippocampus During the Extinction Phase	Change in task-related blood oxygen level dependent (BOLD) responses in the hippocampus during vicarious extinction (specifically for CS+S versus CS- conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the hippocampus region of interest and estimated using a general linear model. A lack of difference between these two task conditions is desirable, indicating processing both task conditions as safety cues.	immediately (45 minutes) after receiving drug
Neural Responses in the CS+R vs CS- Contrast in the Ventromedial Prefrontal Cortex During the Reinstatement Phase	Change in task-related blood oxygen level dependent (BOLD) responses in the ventromedial prefrontal cortex during fear reinstatement, which tests for the return of fear (specifically for CS+R (reinforced) versus CS- (non-reinforced) conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the ventromedial prefrontal cortex region of interest and estimated using a general linear model. Higher mean responses reflect greater discrimination (better able to distinguish between threat and safety cues) between the task conditions.	immediately (45 minutes) after receiving drug
Neural Responses in the CS+S vs CS- Contrast in the Amygdala During the Extinction Phase	Change in task-related blood oxygen level dependent (BOLD) responses in the amygdala during vicarious extinction (specifically for CS+S versus CS- conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the amygdala region of interest and estimated using a general linear model. A lack of difference between these two task conditions is desirable, indicating processing both task conditions as safety cues.	immediately (45 minutes) after receiving drug
Neural Responses in the CS+S vs CS- Contrast in the Insula During the Extinction Phase	Change in task-related blood oxygen level dependent (BOLD) responses in the insula during vicarious extinction (specifically for CS+S versus CS- conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the insula region of interest and estimated using a general linear model. A lack of difference between these two task conditions is desirable, indicating processing both task conditions as safety cues.	immediately (45 minutes) after receiving drug
Neural Responses in the CS+S vs CS- Contrast in the Ventromedial Prefrontal Cortex During the Extinction Phase	Change in task-related blood oxygen level dependent (BOLD) responses in the ventromedial prefrontal cortex during vicarious extinction (specifically for CS+S versus CS- conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the ventromedial prefrontal cortex region of interest and estimated using a general linear model. A lack of difference between these two task conditions is desirable, indicating processing both task conditions as safety cues.	immediately (45 minutes) after receiving drug
Neural Responses in the CS+S vs CS- Contrast in the Anterior Cingulate Cortex During the Extinction Phase	Change in task-related blood oxygen level dependent (BOLD) responses in the anterior cingulate cortex during vicarious extinction (specifically for CS+S versus CS- conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the anterior cingulate cortex region of interest and estimated using a general linear model. A lack of difference between these two task conditions is desirable, indicating processing both task conditions as safety cues.	immediately (45 minutes) after receiving drug
Neural Responses in the CS+S vs CS- Contrast in the Amygdala During the Reinstatement Phase	Change in task-related blood oxygen level dependent (BOLD) responses in the amygdala during fear reinstatement, which tests the return of fear (specifically for CS+S versus CS- conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the amygdala region of interest and estimated using a general linear model. A lack of difference between these two task conditions is desirable, indicating processing both task conditions as safety cues.	immediately (45 minutes) after receiving drug
Neural Responses in the CS+S vs CS- Contrast in the Insula During the Reinstatement Phase	Change in task-related blood oxygen level dependent (BOLD) responses in the insula during fear reinstatement, which tests the return of fear (specifically for CS+S versus CS- conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the insula region of interest and estimated using a general linear model. A lack of difference between these two task conditions is desirable, indicating processing both task conditions as safety cues.	immediately (45 minutes) after receiving drug
Neural Responses in the CS+S vs CS- Contrast in the Hippocampus During the Reinstatement Phase	Change in task-related blood oxygen level dependent (BOLD) responses in the hippocampus during fear reinstatement, which tests the return of fear (specifically for CS+S versus CS- conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the hippocampus region of interest and estimated using a general linear model. A lack of difference between these two task conditions is desirable, indicating processing both task conditions as safety cues.	immediately (45 minutes) after receiving drug
Neural Responses in the CS+S vs CS- Contrast in the Anterior Cingulate Cortex During the Reinstatement Phase	Change in task-related blood oxygen level dependent (BOLD) responses in the anterior cingulate cortex during fear reinstatement, which tests the return of fear (specifically for CS+S versus CS- conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the anterior cingulate cortex region of interest and estimated using a general linear model. A lack of difference between these two task conditions is desirable, indicating processing both task conditions as safety cues.	immediately (45 minutes) after receiving drug
Neural Responses in the CS+S vs CS- Contrast in the Ventromedial Prefrontal Cortex During the Reinstatement Phase	Change in task-related blood oxygen level dependent (BOLD) responses in the ventromedial prefrontal cortex during fear reinstatement, which tests the return of fear (specifically for CS+S versus CS- conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the ventromedial prefrontal cortex region of interest and estimated using a general linear model. A lack of difference between these two task conditions is desirable, indicating processing both task conditions as safety cues.	immediately (45 minutes) after receiving drug
Neural Responses in the CS+R vs CS+S Contrast in the Ventromedial Prefrontal Cortex During the Reinstatement Phase	Change in task-related blood oxygen level dependent (BOLD) responses in the amygdala during fear reinstatement, which tests for the return of fear (specifically for CS+R (reinforced) versus CS+S (non-reinforced) conditions). Changes in BOLD responses refer to differences in neural responses between these two task conditions, which were extracted from the ventromedial prefrontal cortex region of interest and estimated using a general linear model. Higher mean responses reflect greater discrimination (better able to distinguish between threat and safety cues) between the task conditions.	immediately (45 minutes) after receiving drug

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
skin conductance responses (SCR) to vicariously extinguished cue versus vicariously reinforced cue during reinstatement	mean SCR for CS- versus CS+	immediately after the intervention

Collaborators and Investigators

• Sponsor: University of Washington
• Investigators: Principal Investigator: Angela Fang, PhD, University of Washington

Study record dates

Study Major Dates

• Study Start (Actual): June 26, 2023
• Primary Completion (Actual): September 30, 2024
• Study Completion (Actual): September 30, 2024

Study Registration Dates

• First Submitted: July 10, 2023
• First Submitted That Met QC Criteria: July 26, 2023
• First Posted (Actual): August 1, 2023

Study Record Updates

• Last Update Posted (Actual): June 11, 2026
• Last Update Submitted That Met QC Criteria: June 10, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Social Phobia; Social Anxiety Disorder; Intranasal Oxytocin; Social Safety Learning
• Additional Relevant MeSH Terms: Mental Disorders; Phobic Disorders; Anxiety Disorders; Phobia, Social; Physiological Effects of Drugs; Reproductive Control Agents; Oxytocics; Oxytocin
• Other Study ID Numbers: STUDY00013670

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No