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Completed

NCT Number: NCT05968651

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).

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Key information

Conditions

Social Phobia Anxiety Disorders Mental Disorders Phobia, Social Phobic Disorders

Age range

18 year–45 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

University of Washington

Seattle, Washington, 98195, United States

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Oxytocin nasal spray or placebo

Drug

Single acute administration of 24 international units (IU) oxytocin or matching placebo

Primary outcomes

  1. Neural Responses in the CS+R vs CS+S Contrast in the Insula During the Extinction Phase

    Time frame: immediately (45 minutes) after receiving drug

    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.

  2. Neural Responses in the CS+R vs CS+S Contrast in the Hippocampus During the Extinction Phase

    Time frame: immediately (45 minutes) after receiving drug

    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.

  3. Neural Responses in the CS+R vs CS+S Contrast in the Anterior Cingulate Cortex During the Extinction Phase

    Time frame: immediately (45 minutes) after receiving drug

    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.

  4. Neural Responses in the CS+R vs CS+S Contrast in the Ventromedial Prefrontal Cortex During the Extinction Phase

    Time frame: immediately (45 minutes) after receiving drug

    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.

  5. Neural Responses in the CS+R vs CS+S Contrast in the Anterior Cingulate Cortex During the Reinstatement Phase

    Time frame: immediately (45 minutes) after receiving drug

    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.

  6. Neural Responses in the CS+R vs CS+S Contrast in the Insula During the Reinstatement Phase

    Time frame: immediately (45 minutes) after receiving drug

    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.

  7. Neural Responses in the CS+R vs CS+S Contrast in the Hippocampus During the Reinstatement Phase

    Time frame: immediately (45 minutes) after receiving drug

    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.

  8. Neural Responses in the CS+R vs CS+S Contrast in the Amygdala During the Reinstatement Phase

    Time frame: immediately (45 minutes) after receiving drug

    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.

  9. Skin Conductance Responses (SCR) to CS- During Extinction

    Time frame: immediately (45 minutes) after receiving drug

    mean skin conductance responses (SCR) for CS- stimuli during Extinction

  10. Skin Conductance Responses (SCR) to CS+S During Extinction

    Time frame: immediately (45 minutes) after receiving drug

    mean skin conductance responses (SCR) for CS+S stimuli during Extinction

  11. Skin Conductance Responses (SCR) to CS+R During Extinction

    Time frame: immediately (45 minutes) after receiving drug

    mean skin conductance responses (SCR) for CS+R stimuli during Extinction

  12. Skin Conductance Responses (SCR) to CS- During Reinstatement

    Time frame: immediately (45 minutes) after receiving drug

    mean skin conductance responses (SCR) for CS- stimuli during Reinstatement

  13. Skin Conductance Responses (SCR) to CS+S During Reinstatement

    Time frame: immediately (45 minutes) after receiving drug

    mean skin conductance responses (SCR) for CS+S stimuli during Reinstatement

  14. Skin Conductance Responses (SCR) to CS+R During Reinstatement

    Time frame: immediately (45 minutes) after receiving drug

    mean skin conductance responses (SCR) for CS+R stimuli during Reinstatement

  15. Neural Responses in the CS+R vs CS- Contrast in the Insula During the Extinction Phase

    Time frame: immediately (45 minutes) after receiving drug

    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.

  16. Neural Responses in the CS+R vs CS- Contrast in the Amygdala During the Extinction Phase

    Time frame: immediately (45 minutes) after receiving drug

    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.

  17. Neural Responses in the CS+R vs CS+S Contrast in the Ventromedial Prefrontal Cortex During the Reinstatement Phase

    Time frame: immediately (45 minutes) after receiving drug

    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.

  18. Neural Responses in the CS+R vs CS- Contrast in the Hippocampus During the Extinction Phase

    Time frame: immediately (45 minutes) after receiving drug

    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.

  19. Neural Responses in the CS+R vs CS- Contrast in the Anterior Cingulate Cortex During the Extinction Phase

    Time frame: immediately (45 minutes) after receiving drug

    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.

  20. Neural Responses in the CS+R vs CS- Contrast in the Ventromedial Prefrontal Cortex During the Extinction Phase

    Time frame: immediately (45 minutes) after receiving drug

    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.

  21. Neural Responses in the CS+R vs CS- Contrast in the Amygdala During the Reinstatement Phase

    Time frame: immediately (45 minutes) after receiving drug

    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.

  22. Neural Responses in the CS+R vs CS- Contrast in the Insula During the Reinstatement Phase

    Time frame: immediately (45 minutes) after receiving drug

    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.

  23. Neural Responses in the CS+R vs CS- Contrast in the Hippocampus During the Reinstatement Phase

    Time frame: immediately (45 minutes) after receiving drug

    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.

  24. Neural Responses in the CS+R vs CS- Contrast in the Anterior Cingulate Cortex During the Reinstatement Phase

    Time frame: immediately (45 minutes) after receiving drug

    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.

  25. Neural Responses in the CS+S vs CS- Contrast in the Hippocampus During the Extinction Phase

    Time frame: immediately (45 minutes) after receiving drug

    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.

  26. Neural Responses in the CS+R vs CS- Contrast in the Ventromedial Prefrontal Cortex During the Reinstatement Phase

    Time frame: immediately (45 minutes) after receiving drug

    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.

  27. Neural Responses in the CS+S vs CS- Contrast in the Amygdala During the Extinction Phase

    Time frame: immediately (45 minutes) after receiving drug

    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.

  28. Neural Responses in the CS+S vs CS- Contrast in the Insula During the Extinction Phase

    Time frame: immediately (45 minutes) after receiving drug

    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.

  29. Neural Responses in the CS+S vs CS- Contrast in the Ventromedial Prefrontal Cortex During the Extinction Phase

    Time frame: immediately (45 minutes) after receiving drug

    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.

  30. Neural Responses in the CS+S vs CS- Contrast in the Anterior Cingulate Cortex During the Extinction Phase

    Time frame: immediately (45 minutes) after receiving drug

    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.

  31. Neural Responses in the CS+S vs CS- Contrast in the Amygdala During the Reinstatement Phase

    Time frame: immediately (45 minutes) after receiving drug

    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.

  32. Neural Responses in the CS+S vs CS- Contrast in the Insula During the Reinstatement Phase

    Time frame: immediately (45 minutes) after receiving drug

    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.

  33. Neural Responses in the CS+S vs CS- Contrast in the Hippocampus During the Reinstatement Phase

    Time frame: immediately (45 minutes) after receiving drug

    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.

  34. Neural Responses in the CS+S vs CS- Contrast in the Anterior Cingulate Cortex During the Reinstatement Phase

    Time frame: immediately (45 minutes) after receiving drug

    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.

  35. Neural Responses in the CS+S vs CS- Contrast in the Ventromedial Prefrontal Cortex During the Reinstatement Phase

    Time frame: immediately (45 minutes) after receiving drug

    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.

  36. Neural Responses in the CS+R vs CS+S Contrast in the Ventromedial Prefrontal Cortex During the Reinstatement Phase

    Time frame: immediately (45 minutes) after receiving drug

    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.

Sponsors and collaborators

Lead sponsor

University of Washington

Other

Registry information

Important dates

Study start
2023
Primary completion
2024
Study completion
2024
First posted
Aug 1, 2023
Registry last updated
Jun 11, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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