Social Phobia
Conditions
Keywords
Social Phobia, Social Anxiety Disorder, Social Safety Learning, Intranasal Oxytocin
Brief summary
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).
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.
Interventions
Single acute administration of 24 international units (IU) oxytocin or matching placebo
Sponsors
University of Washington
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Neural Responses in the CS+R vs CS+S Contrast in the Insula During the Extinction Phase | 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. |
| Neural Responses in the CS+R vs CS+S Contrast in the Hippocampus During the Extinction Phase | 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. |
| Neural Responses in the CS+R vs CS+S Contrast in the Anterior Cingulate Cortex During the Extinction Phase | 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. |
| Neural Responses in the CS+R vs CS+S Contrast in the Ventromedial Prefrontal Cortex During the Extinction Phase | 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. |
| Neural Responses in the CS+R vs CS+S Contrast in the Anterior Cingulate Cortex During the Reinstatement Phase | 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. |
| Neural Responses in the CS+R vs CS+S Contrast in the Insula During the Reinstatement Phase | 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. |
| Neural Responses in the CS+R vs CS+S Contrast in the Hippocampus During the Reinstatement Phase | 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. |
| Neural Responses in the CS+R vs CS+S Contrast in the Amygdala During the Reinstatement Phase | 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. |
| Skin Conductance Responses (SCR) to CS- During Extinction | immediately (45 minutes) after receiving drug | mean skin conductance responses (SCR) for CS- stimuli during Extinction |
| Skin Conductance Responses (SCR) to CS+S During Extinction | immediately (45 minutes) after receiving drug | mean skin conductance responses (SCR) for CS+S stimuli during Extinction |
| Skin Conductance Responses (SCR) to CS+R During Extinction | immediately (45 minutes) after receiving drug | mean skin conductance responses (SCR) for CS+R stimuli during Extinction |
| Skin Conductance Responses (SCR) to CS- During Reinstatement | immediately (45 minutes) after receiving drug | mean skin conductance responses (SCR) for CS- stimuli during Reinstatement |
| Skin Conductance Responses (SCR) to CS+S During Reinstatement | immediately (45 minutes) after receiving drug | mean skin conductance responses (SCR) for CS+S stimuli during Reinstatement |
| Skin Conductance Responses (SCR) to CS+R During Reinstatement | immediately (45 minutes) after receiving drug | mean skin conductance responses (SCR) for CS+R stimuli during Reinstatement |
| Neural Responses in the CS+R vs CS- Contrast in the Insula During the Extinction Phase | 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. |
| Neural Responses in the CS+R vs CS- Contrast in the Amygdala During the Extinction Phase | 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. |
| Neural Responses in the CS+R vs CS+S Contrast in the Ventromedial Prefrontal Cortex During the Reinstatement Phase | 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. |
| Neural Responses in the CS+R vs CS- Contrast in the Hippocampus During the Extinction Phase | 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. |
| Neural Responses in the CS+R vs CS- Contrast in the Anterior Cingulate Cortex During the Extinction Phase | 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. |
| Neural Responses in the CS+R vs CS- Contrast in the Ventromedial Prefrontal Cortex During the Extinction Phase | 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. |
| Neural Responses in the CS+R vs CS- Contrast in the Amygdala During the Reinstatement Phase | 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. |
| Neural Responses in the CS+R vs CS- Contrast in the Insula During the Reinstatement Phase | 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. |
| Neural Responses in the CS+R vs CS- Contrast in the Hippocampus During the Reinstatement Phase | 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. |
| Neural Responses in the CS+R vs CS- Contrast in the Anterior Cingulate Cortex During the Reinstatement Phase | 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. |
| Neural Responses in the CS+S vs CS- Contrast in the Hippocampus During the Extinction Phase | 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. |
| Neural Responses in the CS+R vs CS- Contrast in the Ventromedial Prefrontal Cortex During the Reinstatement Phase | 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. |
| Neural Responses in the CS+S vs CS- Contrast in the Amygdala During the Extinction Phase | 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. |
| Neural Responses in the CS+S vs CS- Contrast in the Insula During the Extinction Phase | 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. |
| Neural Responses in the CS+S vs CS- Contrast in the Ventromedial Prefrontal Cortex During the Extinction Phase | 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. |
| Neural Responses in the CS+S vs CS- Contrast in the Anterior Cingulate Cortex During the Extinction Phase | 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. |
| Neural Responses in the CS+S vs CS- Contrast in the Amygdala During the Reinstatement Phase | 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. |
| Neural Responses in the CS+S vs CS- Contrast in the Insula During the Reinstatement Phase | 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. |
| Neural Responses in the CS+S vs CS- Contrast in the Hippocampus During the Reinstatement Phase | 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. |
| Neural Responses in the CS+S vs CS- Contrast in the Anterior Cingulate Cortex During the Reinstatement Phase | 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. |
| Neural Responses in the CS+S vs CS- Contrast in the Ventromedial Prefrontal Cortex During the Reinstatement Phase | 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORAngela Fang, PhD
University of Washington
Participant flow
Recruitment details
Participants were recruited from the community via online and print advertisements and through local research volunteer databases.
Pre-assignment details
121 participants were consented and assessed for eligibility. 104 participants were randomized to drug group (10 patients with SAD and 7 healthy participants were excluded due to ineligibility). In the SAD group, 7 did not meet criteria for SAD or SAD was not primary, 3 had active substance use disorders in the past 6 months, 1 had a history of brain lesion, 1 had current psychotherapy, and 1 had past manic episode. In the healthy group, 6 had past depression and 1 had subclinical SAD symptoms.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 24.592233 years STANDARD_DEVIATION 6.851988 |
| Depression Anxiety Stress Scale | 45.304348 units on a scale STANDARD_DEVIATION 23.599759 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 83 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Liebowitz Social Anxiety Scale (LSAS) | 82.296296 units on a scale STANDARD_DEVIATION 17.065067 |
| Race/Ethnicity, Customized Asian | 48 Participants |
| Race/Ethnicity, Customized Black | 3 Participants |
| Race/Ethnicity, Customized Hawaiian/Pacific Islander | 2 Participants |
| Race/Ethnicity, Customized Hispanic | 11 Participants |
| Race/Ethnicity, Customized Middle eastern | 1 Participants |
| Race/Ethnicity, Customized Native | 1 Participants |
| Race/Ethnicity, Customized Native, black | 1 Participants |
| Race/Ethnicity, Customized Other | 1 Participants |
| Race/Ethnicity, Customized White | 35 Participants |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | 10 Participants |
| skin conductance responses (SCR) to CS- during Acquisition | 0.050110 microsiemens STANDARD_DEVIATION 0.117717 |
| skin conductance responses (SCR) to CS+ during Acquisition | 0.060565 microsiemens STANDARD_DEVIATION 0.138834 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 0 / 28 | 0 / 28 | 0 / 24 |
| other Total, other adverse events | 11 / 23 | 17 / 28 | 16 / 28 | 13 / 24 |
| serious Total, serious adverse events | 0 / 23 | 0 / 28 | 0 / 28 | 0 / 24 |
Outcome results
None listed