Psychological Stress
Conditions
Keywords
stress, sex, fear, generalization, cortisol, alpha-amylase, estradiol, progesterone
Brief summary
The impact of well-known risk factors for such disorders (stress, biological sex, anxiety-related dispositions) on fear generalization will be examined. Findings from this study may provide insight into how these risk factors influence the development and/or maintenance of psychological disorders that involve overgeneralization of fear and could facilitate future approaches to their treatment.
Detailed description
Many researchers approach the etiology of trauma-, stressor-, and anxiety-related mental disorders from the perspective of classical conditioning processes gone awry. According to this view, abnormal associative relationships between neutral, conditioned stimuli (CSs) and aversive, unconditioned stimuli (USs) underlie pathological anxiety and result in unusually intense fear memories or fear memories that cannot be properly extinguished. Recent work has expanded this view by showing that many psychological disorders involving pathological anxiety are associated with an exaggerated form of the commonly adaptive classical conditioning phenomenon, stimulus generalization, leading individuals with such disorders to respond with fear and anxiety to a variety of environmental contexts and cues that should not be threatening. Few studies have been conducted in humans to better understand the process of fear generalization, and factors that might influence susceptibility to overgeneralize fear have yet to be assessed. It is well-known that stress, biological sex, and anxiety-related dispositions of an individual increase one's susceptibility for pathological anxiety and significantly impact fear learning; thus, it is possible that such factors, alone or in combination, contribute to clinical anxiety by influencing fear generalization processes. Aim 1 of the present study is to determine the effects of acute stress and its physiological correlates on fear generalization in human participants. Because acute stress profoundly impacts cognitive brain areas that underlie generalization, it is predicted that acute stress will enhance or impair fear generalization, depending on when the stressor is administered relative to fear learning. Aim 2 is to assess the role of biological sex in fear generalization and acute stress-induced changes in such processes. Females are more likely than males to develop several psychological disorders that involve pathological anxiety, and research has consistently reported sex-related differences in fear learning and stress-induced alterations of fear learning, effects that have been associated with ovarian hormones. Thus, it is predicted that females will exhibit greater fear generalization than males that will be impacted differently by stress. It is also hypothesized that the observed effects will correlate with estradiol and progesterone in females. The final aim of this project (Aim 3) is to evaluate the relationship between childhood stress, dispositional anxiety, and fear generalization. Early life stress has been repeatedly associated with altered stress responses and the development of anxiety-related phenotypes, yet the influence of childhood stress and trait anxiety on fear generalization have yet to be examined. This study will be the first to examine how several factors that are known to increase susceptibility for trauma-, stressor, and anxiety-related psychological disorders impact fear generalization in human subjects. The resulting findings will provide important insight into the etiology of such disorders, which could aid future approaches to their treatment.
Interventions
BEHAVIORALStress immediately before learning in males
Male participants will be exposed to the socially evaluated cold pressor test immediately prior to fear learning. Participants will place their dominant hand in a bath of ice cold water for up to 3 minutes. The participants will also be informed that they are being videotaped for analysis of facial expressions and be asked to stare at a camera throughout the manipulation. Immediately following the acute stressor, participants will undergo the acquisition phase of fear conditioning.
BEHAVIORALSham control immediately before learning in males
Male participants will be exposed to the sham control condition (no stress) immediately prior to fear learning. Participants will place their dominant hand in a bath of lukewarm water for up to 3 minutes. Immediately following the sham control condition, participants will undergo the acquisition phase of fear conditioning.
BEHAVIORALStress 30 minutes before learning in males
Male participants will be exposed to the socially evaluated cold pressor test 30 minutes prior to fear learning. Participants will place their dominant hand in a bath of ice cold water for up to 3 minutes. The participants will also be informed that they are being videotaped for analysis of facial expressions and be asked to stare at a camera throughout the manipulation. Thirty minutes following the acute stressor, participants will undergo the acquisition phase of fear conditioning.
BEHAVIORALSham control 30 minutes before learning in males
Male participants will be exposed to the sham control condition (no stress) 30 minutes prior to fear learning. Participants will place their dominant hand in a bath of lukewarm water for up to 3 minutes. Thirty minutes following the sham control condition, participants will undergo the acquisition phase of fear conditioning.
BEHAVIORALStress immediately before learning in females
Female participants will be exposed to the socially evaluated cold pressor test immediately prior to fear learning. Participants will place their dominant hand in a bath of ice cold water for up to 3 minutes. The participants will also be informed that they are being videotaped for analysis of facial expressions and be asked to stare at a camera throughout the manipulation. Immediately following the acute stressor, participants will undergo the acquisition phase of fear conditioning.
BEHAVIORALSham control immediately before learning in females
Female participants will be exposed to the sham control condition (no stress) immediately prior to fear learning. Participants will place their dominant hand in a bath of lukewarm water for up to 3 minutes. Immediately following the sham control condition, participants will undergo the acquisition phase of fear conditioning.
BEHAVIORALStress 30 minutes before learning in females
Female participants will be exposed to the socially evaluated cold pressor test 30 minutes prior to fear learning. Participants will place their dominant hand in a bath of ice cold water for up to 3 minutes. The participants will also be informed that they are being videotaped for analysis of facial expressions and be asked to stare at a camera throughout the manipulation. Thirty minutes following the acute stressor, participants will undergo the acquisition phase of fear conditioning.
BEHAVIORALSham control 30 minutes before learning in females
Female participants will be exposed to the sham control condition (no stress) 30 minutes prior to fear learning. Participants will place their dominant hand in a bath of lukewarm water for up to 3 minutes. Thirty minutes following the sham control condition, participants will undergo the acquisition phase of fear conditioning.
Sponsors
National Institute of Mental Health (NIMH)
Ohio Northern University
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* 18 years of age * Registered student at Ohio Northern University in Ada, Ohio
Exclusion criteria
* Regular use of tobacco or recreational drugs (e.g., marijuana, cocaine, heroin, etc.) * Previous diagnosis of Raynaud's disease or peripheral vascular disease * Previous diagnosis of skin diseases (e.g., severe psoriasis, eczema, scleroderma) * History of syncope or vasovagal response to stress * History of any heart conditions or cardiovascular issues (e.g., high blood pressure) * History of severe head trauma * Current treatment with narcotics, beta-blockers, or steroids * Previous diagnosis of substance use disorder * Regular nightshift work * Hearing loss * Consumed alcohol in past 24 hours * Engaged in strenuous exercise in past 24 hours * Ate or drank anything but water in past 2 hours
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | Average of ratings from all trials on Day 2 | Participants were exposed to 3 blocks of trials, and each block included 1 presentation of the CS+, one presentation of each of 7 generalization stimuli (GSs), and one presentation of the CS-. Participants were instructed to press, within 3 seconds of stimulus onset, a button marked + if they expected the stimulus to be followed by the US, a button marked - if they did not expect the stimulus to be followed by the US, or a button marked 0 if they were uncertain. For the purpose of data analysis, + was scored as +1, - was scored as -1, and 0 was scored as 0. Average expectancy ratings for each stimulus across all 3 blocks were used as an indicator of fear. Greater scores for the generalization stimuli (GS) indicated a greater generalization of fear. |
| US Expectancy Ratings to CS+ and CS- During Acquisition | Average of the ratings from trial block 13, trial block 14, trial block 15, and trial block 16 on Day 1 | Participants were exposed to 16 blocks of trials, and each block included 1 presentation of the CS+ and one presentation of the CS-. During the last 12 blocks, CS+ trials included the presentation of an aversive US. During each trial, participants pressed, within 3 seconds of stimulus onset, a button marked + if they expected the stimulus to be followed by the US, a button marked - if they did not expect the stimulus to be followed by the US, or a button marked 0 if they were uncertain. For the purpose of data analysis, + was scored as +1, - were scored as -1, and 0 was scored as 0. Average expectancy ratings during the last 4 blocks of trials were used as an indicator of fear learning (greater responses to the CS+, relative to the CS-, indicated greater learning). |
| Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | Average of responses from all trials on Day 2 | Electrodermal activity was measured following presentation of the CS+, 7 generalization stimuli (GSs), and CS- during generalization testing on Day 2. Participants were exposed to 3 blocks of trials, with each block including a single presentation of each stimulus. For each block, skin conductance responses were quantified by calculating the average increase in electrodermal activity (from a 1 s pre-stimulus baseline) 3-6 s after onset of the CS+, 7 GSs, or CS- onset.. Average skin conductance responses to each stimulus across all 3 blocks were used as an indicator of fear expression. Greater scores for the generalization stimuli (GS) indicated a greater generalization of fear. |
| Fear-potentiated Startle Responses to the CS+ and CS- During Acquisition | Average of the responses from trial block 13, trial block 14, trial block 15, and trial block 16 on Day 1 | Peak eyeblink startle responses 20-200 ms following presentation of a startle probe were measured. Startle responses were assessed for each of 3 trial types: (1) following the startle probe alone \[noise alone (NA) trials\], (2) following the CS+ and startle probe (CS+ trials), and (3) following the CS- and startle probe (CS- trials). Participants were exposed to 16 blocks of trials, and each block included 1 presentation of each trial type. During the last 12 blocks, CS+ trials also included the presentation of an aversive US. For each block, startle responses to NA trials were subtracted from startle responses to CS+ trials and from startle responses to CS- trials to create 2 separate fear-potentiated startle response measures: 1 for the CS+ and 1 for the CS-. Average fear-potentiated startle responses to the CS+ and CS- during the last 4 blocks of trials were used as an indicator of fear learning (greater responses to the CS+, relative to the CS-, indicated greater learning). |
| Skin Conductance Responses to CS+ and CS- During Acquisition | Average of the responses from trial block 13, trial block 14, trial block 15, and trial block 16 on Day 1 | Electrodermal activity was measured following presentation of the CS+ and CS- during acquisition on Day 1. Participants were exposed to 16 blocks of trials, with each block including a single presentation of each stimulus. During the last 12 blocks, CS+ trials included the presentation of an aversive US. For each block, skin conductance responses were quantified by calculating the average increase in electrodermal activity (from a 1 s pre-stimulus baseline) 3-6 s after CS+ or CS- onset. Average skin conductance responses to the CS+ and CS- during the last 4 blocks of trials were used as an indicator of fear learning (greater responses to the CS+, relative to the CS-, indicated greater learning). |
| EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | Average of responses from all trials on Day 2 | Peak eyeblink startle responses 20-200 ms following the presentation of a startle probe were measured. Startle responses were assessed for each of 10 trial types: (1) following the startle probe alone \[noise alone (NA) trials\], (2) following the CS+ and startle probe (CS+ trials), (3) following each of 7 generalization stimuli and startle probe (GS trials), and (4) following the CS- and startle probe (CS- trials). Participants were exposed to 3 blocks of trials, and each block included 1 presentation of each trial type. For each block, startle responses to the NA trials were subtracted from startle responses to the CS+, GSs, and CS- trials to create separate fear-potentiated startle response measures for each of the 9 different stimuli. Average fear-potentiated startle responses to each stimulus across all 3 blocks were used as an indicator of fear expression. Greater scores for the generalization stimuli (GS) indicated a greater generalization of fear. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Average Subjective Stress, as Assessed by Verbal Self Report | Stress or sham control condition on Day 1 | During the stress or sham control manipulation, participants rated the stressfulness of the water bath at 1-minute intervals on an 11-point scale ranging from 0-10, with 0 = lack of stress and 10 = unbearable stress. The obtained ratings were averaged and analyzed. Greater ratings indicated greater subjective stress during the stressor. |
| Change in Baseline Salivary Alpha-amylase (U/ml) | Day 1 (change from baseline to immediately after stress) | Saliva samples were collected from participants prior to undergoing the stress or sham control condition (baseline) and then immediately after the manipulation. The change in salivary alpha-amylase levels was analyzed. Greater levels indicated greater alpha-amylase responses to stress. |
| Change in Baseline Salivary Cortisol (Nmol/l) | Day 1 (change from baseline to 25 min post-stress) | Saliva samples were collected from participants prior to undergoing the stress or sham control condition (baseline) and then 25 min later. The change in salivary cortisol levels was analyzed. Greater levels indicated greater cortisol responses to stress. |
| Average Subjective Pain, as Assessed by Verbal Self Report | Stress or sham control condition on Day 1 | During the stress or sham control manipulation, participants rated the painfulness of the water bath at 1-minute intervals on an 11-point scale ranging from 0-10, with 0 = lack of pain and 10 = unbearable pain. The obtained ratings were averaged and analyzed. Greater ratings indicated greater subjective pain during the stressor. |
| Change in Heart Rate (Bpm) | Day 1 (change from baseline to during stress or sham control manipulation) | Heart rate (bpm) measurements were aken via the PPG module of the Biopac MP150 system from participants prior to undergoing the stress or sham control condition (baseline) and then halfway through the manipulation.The change in heart rate was analyzed. |
| Change in Salivary Progesterone (pg/ml) | Day 1 (change from baseline to 25 min post-stress) | Saliva samples were collected from female participants prior to undergoing the stress or sham control condition (baseline) and then 25 min later. The change in salivary progesterone levels were analyzed. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Salivary Estradiol (pg/ml) | Average across Day 1 (baseline) and Day 2 (baseline) | Salivary estradiol (pg/ml) was measured by enzyme immunoassay (Salimetrics LLC) performed on saliva samples collected from female participants on Days 1 and 2. |
| PTSD Checklist - Civilian Version | Day 2 - following generalization testing | The PTSD Checklist - Civilian Version was administered following generalization testing on Day 2. The checklist is a 17-item measure of symptoms of post-traumatic stress disorder (PTSD). The minimum score is 0, and the maximum score is 80. Greater scores reflect greater symptoms related to PTSD. |
| Center for Epidemiological Studies Depression Scale (CES-D) | Day 2 - following generalization testing | The Center for Epidemiological Studies Depression Scale (CES-D) was administered following generalization testing on Day 2. The CES-D is a 20-item measure of symptoms of depression. The possible range for scores is 0-60 with higher scores suggesting more severe symptoms of depression. |
| Anxiety Sensitivity Index | Day 2 - following generalization testing | The Anxiety Sensitivity Index (ASI) was administered following generalization testing on Day 2. The ASI consists of 18 items and yields a score that reflects an individual's dispositional anxiety sensitivity. The minimum score is 0, and the maximum score is 72. Greater scores reflect a greater sensitivity to anxiety. |
| Childhood Trauma Questionnaire (CTQ) | Day 2 - following generalization testing | The Childhood Trauma Questionnaire (CTQ) was administered following generalization testing on Day 2. The questionnaire consists of 25 items and yields a score between 25 and 125. Higher scores represent greater levels of childhood trauma exposure. |
| State Anxiety | Day 2 - following generalization testing | The Spielberger State-Trait Anxiety Inventory (STAI) was administered following generalization testing on Day 2. The STAI provides scores (20-80) for state and trait anxiety. State anxiety was used for this measure and was a sum of 20 items from the STAI. The minimum score for state anxiety was 20, and the maximum score was 80. Higher scores represented higher levels of state anxiety. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Stress, Immediate, Males Stress immediately before learning in males
Stress immediately before learning in males: Male participants will be exposed to the socially evaluated cold pressor test immediately prior to fear learning. Participants will place their dominant hand in a bath of ice cold water for up to 3 minutes. The participants will also be informed that they are being videotaped for analysis of facial expressions and be asked to stare at a camera throughout the manipulation. Immediately following the acute stressor, participants will undergo the acquisition phase of fear conditioning. | 56 |
| Stress, Delayed, Males Stress 30 minutes before learning in males
Stress 30 minutes before learning in males: Male participants will be exposed to the socially evaluated cold pressor test 30 minutes prior to fear learning. Participants will place their dominant hand in a bath of ice cold water for up to 3 minutes. The participants will also be informed that they are being videotaped for analysis of facial expressions and be asked to stare at a camera throughout the manipulation. Thirty minutes following the acute stressor, participants will undergo the acquisition phase of fear conditioning. | 59 |
| Sham Control, Immediate, Males Sham control immediately before learning in males
Sham control immediately before learning in males: Male participants will be exposed to the sham control condition (no stress) immediately prior to fear learning. Participants will place their dominant hand in a bath of lukewarm water for up to 3 minutes. Immediately following the sham control condition, participants will undergo the acquisition phase of fear conditioning. | 58 |
| Sham Control, Delayed, Males Sham control 30 minutes before learning in males
Sham control 30 minutes before learning in males: Male participants will be exposed to the sham control condition (no stress) 30 minutes prior to fear learning. Participants will place their dominant hand in a bath of lukewarm water for up to 3 minutes. Thirty minutes following the sham control condition, participants will undergo the acquisition phase of fear conditioning. | 57 |
| Stress, Immediate, Females Stress immediately before learning in females
Stress immediately before learning in females: Female participants will be exposed to the socially evaluated cold pressor test immediately prior to fear learning. Participants will place their dominant hand in a bath of ice cold water for up to 3 minutes. The participants will also be informed that they are being videotaped for analysis of facial expressions and be asked to stare at a camera throughout the manipulation. Immediately following the acute stressor, participants will undergo the acquisition phase of fear conditioning. | 97 |
| Stress, Delayed, Females Stress 30 minutes before learning in females
Stress 30 minutes before learning in females: Female participants will be exposed to the socially evaluated cold pressor test 30 minutes prior to fear learning. Participants will place their dominant hand in a bath of ice cold water for up to 3 minutes. The participants will also be informed that they are being videotaped for analysis of facial expressions and be asked to stare at a camera throughout the manipulation. Thirty minutes following the acute stressor, participants will undergo the acquisition phase of fear conditioning. | 87 |
| Sham Control, Immediate, Females Sham control immediately before learning in females
Sham control immediately before learning in females: Female participants will be exposed to the sham control condition (no stress) immediately prior to fear learning. Participants will place their dominant hand in a bath of lukewarm water for up to 3 minutes. Immediately following the sham control condition, participants will undergo the acquisition phase of fear conditioning. | 94 |
| Sham Control, Delayed, Females Sham control 30 minutes before learning in females
Sham control 30 minutes before learning in females: Female participants will be exposed to the sham control condition (no stress) 30 minutes prior to fear learning. Participants will place their dominant hand in a bath of lukewarm water for up to 3 minutes. Thirty minutes following the sham control condition, participants will undergo the acquisition phase of fear conditioning. | 98 |
| Total | 606 |
Baseline characteristics
| Characteristic | Stress, Immediate, Males | Sham Control, Delayed, Females | Stress, Delayed, Males | Sham Control, Immediate, Males | Total | Sham Control, Immediate, Females | Stress, Immediate, Females | Stress, Delayed, Females | Sham Control, Delayed, Males |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 19.38 years STANDARD_DEVIATION 1.65 | 18.97 years STANDARD_DEVIATION 1.16 | 19.95 years STANDARD_DEVIATION 1.79 | 19.19 years STANDARD_DEVIATION 1.26 | 19.19 years STANDARD_DEVIATION 1.68 | 18.84 years STANDARD_DEVIATION 0.86 | 18.77 years STANDARD_DEVIATION 0.98 | 19.39 years STANDARD_DEVIATION 3.06 | 19.61 years STANDARD_DEVIATION 1.32 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 4 Participants | 2 Participants | 2 Participants | 20 Participants | 6 Participants | 4 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 55 Participants | 94 Participants | 57 Participants | 56 Participants | 586 Participants | 88 Participants | 93 Participants | 87 Participants | 56 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height | 70 inches STANDARD_DEVIATION 2.83645 | 65.0332 inches STANDARD_DEVIATION 3.00121 | 70.3051 inches STANDARD_DEVIATION 3.07523 | 71.1724 inches STANDARD_DEVIATION 2.34811 | 67.1894 inches STANDARD_DEVIATION 3.9486 | 65.734 inches STANDARD_DEVIATION 3.05567 | 64.7526 inches STANDARD_DEVIATION 3.06197 | 65.1552 inches STANDARD_DEVIATION 2.92375 | 70.5088 inches STANDARD_DEVIATION 3.26301 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 4 Participants | 3 Participants | 2 Participants | 27 Participants | 1 Participants | 6 Participants | 6 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 2 Participants | 7 Participants | 4 Participants | 29 Participants | 3 Participants | 3 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 50 Participants | 90 Participants | 48 Participants | 52 Participants | 546 Participants | 90 Participants | 87 Participants | 79 Participants | 50 Participants |
| Region of Enrollment United States | 56 participants | 98 participants | 59 participants | 58 participants | 606 participants | 94 participants | 97 participants | 87 participants | 57 participants |
| Sex: Female, Male Female | 0 Participants | 98 Participants | 0 Participants | 0 Participants | 376 Participants | 94 Participants | 97 Participants | 87 Participants | 0 Participants |
| Sex: Female, Male Male | 56 Participants | 0 Participants | 59 Participants | 58 Participants | 230 Participants | 0 Participants | 0 Participants | 0 Participants | 57 Participants |
| Weight | 175.6429 pounds STANDARD_DEVIATION 39.5481 | 153.4286 pounds STANDARD_DEVIATION 41.21405 | 175.7458 pounds STANDARD_DEVIATION 32.5198 | 182.5862 pounds STANDARD_DEVIATION 37.76522 | 162.5990 pounds STANDARD_DEVIATION 40.3379 | 154.7553 pounds STANDARD_DEVIATION 36.01424 | 146.1237 pounds STANDARD_DEVIATION 34.88889 | 149.2989 pounds STANDARD_DEVIATION 32.9302 | 192.8772 pounds STANDARD_DEVIATION 44.194 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 56 | 0 / 59 | 0 / 58 | 0 / 57 | 0 / 97 | 0 / 87 | 0 / 94 | 0 / 98 |
| other Total, other adverse events | 0 / 56 | 0 / 59 | 0 / 58 | 0 / 57 | 0 / 97 | 0 / 87 | 0 / 94 | 0 / 98 |
| serious Total, serious adverse events | 0 / 56 | 0 / 59 | 0 / 58 | 0 / 57 | 0 / 97 | 0 / 87 | 0 / 94 | 0 / 98 |
Outcome results
Primary
EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing
Peak eyeblink startle responses 20-200 ms following the presentation of a startle probe were measured. Startle responses were assessed for each of 10 trial types: (1) following the startle probe alone \[noise alone (NA) trials\], (2) following the CS+ and startle probe (CS+ trials), (3) following each of 7 generalization stimuli and startle probe (GS trials), and (4) following the CS- and startle probe (CS- trials). Participants were exposed to 3 blocks of trials, and each block included 1 presentation of each trial type. For each block, startle responses to the NA trials were subtracted from startle responses to the CS+, GSs, and CS- trials to create separate fear-potentiated startle response measures for each of the 9 different stimuli. Average fear-potentiated startle responses to each stimulus across all 3 blocks were used as an indicator of fear expression. Greater scores for the generalization stimuli (GS) indicated a greater generalization of fear.
Time frame: Average of responses from all trials on Day 2
Population: The overall number of participants analyzed is not consistent with the numbers in the participant flow module. Some fear-potentiated startle responses were unable to be obtained from participants due to technical issues (e.g., poor electrode conductance).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Stress, Immediate, Males, CS+ | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 52.059 Fear-potentiated startle (microvolts) | Standard Error 9.552 |
| Stress, Immediate, Males, CS- | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 42.389 Fear-potentiated startle (microvolts) | Standard Error 8.467 |
| Stress, Delayed, Males, CS+ | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 24.461 Fear-potentiated startle (microvolts) | Standard Error 8.215 |
| Stress, Delayed, Males, CS- | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 36.099 Fear-potentiated startle (microvolts) | Standard Error 7.563 |
| Sham Control, Immediate, Males, CS+ | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 25.637 Fear-potentiated startle (microvolts) | Standard Error 7.085 |
| Sham Control, Immediate, Males, CS- | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 13.225 Fear-potentiated startle (microvolts) | Standard Error 7.13 |
| Sham Control, Delayed, Males, CS+ | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 36.013 Fear-potentiated startle (microvolts) | Standard Error 7.759 |
| Sham Control, Delayed, Males, CS- | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 16.838 Fear-potentiated startle (microvolts) | Standard Error 7.797 |
| Stress, Immediate, Females, CS+ | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 19.063 Fear-potentiated startle (microvolts) | Standard Error 7.897 |
| Stress, Immediate, Females, CS- | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 51.595 Fear-potentiated startle (microvolts) | Standard Error 9.552 |
| Stress, Delayed, Females, CS+ | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 47.292 Fear-potentiated startle (microvolts) | Standard Error 8.467 |
| Stress, Delayed, Females, CS- | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 23.265 Fear-potentiated startle (microvolts) | Standard Error 8.215 |
| Sham Control, Immediate, Females, CS+ | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 26.790 Fear-potentiated startle (microvolts) | Standard Error 7.563 |
| Sham Control, Immediate, Females, CS- | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 17.900 Fear-potentiated startle (microvolts) | Standard Error 7.085 |
| Sham Control, Delayed, Females, CS+ | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 17.642 Fear-potentiated startle (microvolts) | Standard Error 7.13 |
| Sham Control, Delayed, Females, CS- | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 18.197 Fear-potentiated startle (microvolts) | Standard Error 7.759 |
| Stress, Delayed, Males, GS7 | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 17.472 Fear-potentiated startle (microvolts) | Standard Error 7.797 |
| Stress, Delayed, Males, CS- | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 18.542 Fear-potentiated startle (microvolts) | Standard Error 7.897 |
| Sham Control, Immediate, Males, CS+ | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 59.295 Fear-potentiated startle (microvolts) | Standard Error 10.317 |
| Sham Control, Immediate, Males, GS1 | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 36.931 Fear-potentiated startle (microvolts) | Standard Error 9.146 |
| Sham Control, Immediate, Males, GS2 | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 29.738 Fear-potentiated startle (microvolts) | Standard Error 8.874 |
| Sham Control, Immediate, Males, GS3 | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 32.878 Fear-potentiated startle (microvolts) | Standard Error 8.169 |
| Sham Control, Immediate, Males, GS4 | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 31.296 Fear-potentiated startle (microvolts) | Standard Error 7.652 |
| Sham Control, Immediate, Males, GS5 | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 28.073 Fear-potentiated startle (microvolts) | Standard Error 7.701 |
| Sham Control, Immediate, Males, GS6 | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 32.893 Fear-potentiated startle (microvolts) | Standard Error 8.38 |
| Sham Control, Immediate, Males, GS7 | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 21.807 Fear-potentiated startle (microvolts) | Standard Error 8.422 |
| Sham Control, Immediate, Males, CS- | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 25.547 Fear-potentiated startle (microvolts) | Standard Error 8.529 |
| Sham Control, Delayed, Males, CS+ | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 68.576 Fear-potentiated startle (microvolts) | Standard Error 9.668 |
| Sham Control, Delayed, Males, GS1 | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 52.235 Fear-potentiated startle (microvolts) | Standard Error 8.57 |
| Sham Control, Delayed, Males, GS2 | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 36.234 Fear-potentiated startle (microvolts) | Standard Error 8.315 |
| Sham Control, Delayed, Males, GS3 | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 33.031 Fear-potentiated startle (microvolts) | Standard Error 7.655 |
| Sham Control, Delayed, Males, GS4 | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 37.434 Fear-potentiated startle (microvolts) | Standard Error 7.171 |
| Sham Control, Delayed, Males, GS5 | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 22.264 Fear-potentiated startle (microvolts) | Standard Error 7.216 |
| Sham Control, Delayed, Males, GS6 | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 29.489 Fear-potentiated startle (microvolts) | Standard Error 7.853 |
| Sham Control, Delayed, Males, GS7 | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 27.508 Fear-potentiated startle (microvolts) | Standard Error 7.892 |
| Sham Control, Delayed, Males, CS- | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 35.165 Fear-potentiated startle (microvolts) | Standard Error 7.993 |
| Stress, Immediate, Females, CS+ | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 59.043 Fear-potentiated startle (microvolts) | Standard Error 7.245 |
| Stress, Immediate, Females, GS1 | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 49.511 Fear-potentiated startle (microvolts) | Standard Error 6.422 |
| Stress, Immediate, Females, GS2 | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 37.996 Fear-potentiated startle (microvolts) | Standard Error 6.231 |
| Stress, Immediate, Females, GS3 | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 38.498 Fear-potentiated startle (microvolts) | Standard Error 5.737 |
| Stress, Immediate, Females, GS4 | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 32.051 Fear-potentiated startle (microvolts) | Standard Error 5.374 |
| Stress, Immediate, Females, GS5 | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 26.428 Fear-potentiated startle (microvolts) | Standard Error 5.408 |
| Stress, Immediate, Females, GS6 | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 48.603 Fear-potentiated startle (microvolts) | Standard Error 5.885 |
| Stress, Immediate, Females, GS7 | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 32.181 Fear-potentiated startle (microvolts) | Standard Error 5.914 |
| Stress, Immediate, Females, CS- | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 19.585 Fear-potentiated startle (microvolts) | Standard Error 5.99 |
| Stress, Delayed, Females, CS+ | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 57.618 Fear-potentiated startle (microvolts) | Standard Error 7.563 |
| Stress, Delayed, Females, GS1 | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 51.025 Fear-potentiated startle (microvolts) | Standard Error 6.704 |
| Stress, Delayed, Females, GS2 | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 31.866 Fear-potentiated startle (microvolts) | Standard Error 6.505 |
| Stress, Delayed, Females, GS3 | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 36.741 Fear-potentiated startle (microvolts) | Standard Error 5.988 |
| Stress, Delayed, Females, GS4 | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 26.989 Fear-potentiated startle (microvolts) | Standard Error 5.609 |
| Stress, Delayed, Females, GS5 | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 23.399 Fear-potentiated startle (microvolts) | Standard Error 5.645 |
| Stress, Delayed, Females, GS6 | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 42.591 Fear-potentiated startle (microvolts) | Standard Error 6.143 |
| Stress, Delayed, Females, GS7 | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 25.380 Fear-potentiated startle (microvolts) | Standard Error 6.173 |
| Stress, Delayed, Females, CS- | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 28.132 Fear-potentiated startle (microvolts) | Standard Error 6.252 |
| Sham Control, Immediate, Females, CS+ | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 51.693 Fear-potentiated startle (microvolts) | Standard Error 7.148 |
| Sham Control, Immediate, Females, GS1 | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 49.296 Fear-potentiated startle (microvolts) | Standard Error 6.336 |
| Sham Control, Immediate, Females, GS2 | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 29.101 Fear-potentiated startle (microvolts) | Standard Error 6.148 |
| Sham Control, Immediate, Females, GS3 | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 36.858 Fear-potentiated startle (microvolts) | Standard Error 5.66 |
| Sham Control, Immediate, Females, GS4 | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 28.705 Fear-potentiated startle (microvolts) | Standard Error 5.302 |
| Sham Control, Immediate, Females, GS5 | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 24.520 Fear-potentiated startle (microvolts) | Standard Error 5.335 |
| Sham Control, Immediate, Females, GS6 | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 37.415 Fear-potentiated startle (microvolts) | Standard Error 5.806 |
| Sham Control, Immediate, Females, GS7 | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 28.944 Fear-potentiated startle (microvolts) | Standard Error 5.835 |
| Sham Control, Immediate, Females, CS- | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 24.180 Fear-potentiated startle (microvolts) | Standard Error 5.909 |
| Sham Control, Delayed, Females, CS+ | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 65.451 Fear-potentiated startle (microvolts) | Standard Error 7.101 |
| Sham Control, Delayed, Females, GS1 | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 61.473 Fear-potentiated startle (microvolts) | Standard Error 6.294 |
| Sham Control, Delayed, Females, GS2 | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 40.557 Fear-potentiated startle (microvolts) | Standard Error 6.107 |
| Sham Control, Delayed, Females, GS3 | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 42.141 Fear-potentiated startle (microvolts) | Standard Error 5.622 |
| Sham Control, Delayed, Females, GS4 | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 30.156 Fear-potentiated startle (microvolts) | Standard Error 5.267 |
| Sham Control, Delayed, Females, GS5 | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 34.117 Fear-potentiated startle (microvolts) | Standard Error 5.3 |
| Sham Control, Delayed, Females, GS6 | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 43.093 Fear-potentiated startle (microvolts) | Standard Error 5.768 |
| Sham Control, Delayed, Females, GS7 | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 34.696 Fear-potentiated startle (microvolts) | Standard Error 5.796 |
| Sham Control, Delayed, Females, CS- | EMG Responses to CS+, CS-, and Generalization Stimuli During Generalization Testing | 42.714 Fear-potentiated startle (microvolts) | Standard Error 5.87 |
p-value: 0.931ANOVA
Primary
Fear-potentiated Startle Responses to the CS+ and CS- During Acquisition
Peak eyeblink startle responses 20-200 ms following presentation of a startle probe were measured. Startle responses were assessed for each of 3 trial types: (1) following the startle probe alone \[noise alone (NA) trials\], (2) following the CS+ and startle probe (CS+ trials), and (3) following the CS- and startle probe (CS- trials). Participants were exposed to 16 blocks of trials, and each block included 1 presentation of each trial type. During the last 12 blocks, CS+ trials also included the presentation of an aversive US. For each block, startle responses to NA trials were subtracted from startle responses to CS+ trials and from startle responses to CS- trials to create 2 separate fear-potentiated startle response measures: 1 for the CS+ and 1 for the CS-. Average fear-potentiated startle responses to the CS+ and CS- during the last 4 blocks of trials were used as an indicator of fear learning (greater responses to the CS+, relative to the CS-, indicated greater learning).
Time frame: Average of the responses from trial block 13, trial block 14, trial block 15, and trial block 16 on Day 1
Population: The overall number of participants analyzed is not consistent with the numbers in the participant flow module. Some fear-potentiated startle responses were unable to be obtained from participants due to technical issues (e.g., poor electrode conductance).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Stress, Immediate, Males, CS+ | Fear-potentiated Startle Responses to the CS+ and CS- During Acquisition | 52.059 Fear-potentiated startle (microvolts) | Standard Error 9.46 |
| Stress, Immediate, Males, CS- | Fear-potentiated Startle Responses to the CS+ and CS- During Acquisition | 19.162 Fear-potentiated startle (microvolts) | Standard Error 7.955 |
| Stress, Delayed, Males, CS+ | Fear-potentiated Startle Responses to the CS+ and CS- During Acquisition | 44.388 Fear-potentiated startle (microvolts) | Standard Error 9.46 |
| Stress, Delayed, Males, CS- | Fear-potentiated Startle Responses to the CS+ and CS- During Acquisition | 9.732 Fear-potentiated startle (microvolts) | Standard Error 7.955 |
| Sham Control, Immediate, Males, CS+ | Fear-potentiated Startle Responses to the CS+ and CS- During Acquisition | 42.123 Fear-potentiated startle (microvolts) | Standard Error 9.972 |
| Sham Control, Immediate, Males, CS- | Fear-potentiated Startle Responses to the CS+ and CS- During Acquisition | 20.215 Fear-potentiated startle (microvolts) | Standard Error 8.385 |
| Sham Control, Delayed, Males, CS+ | Fear-potentiated Startle Responses to the CS+ and CS- During Acquisition | 47.904 Fear-potentiated startle (microvolts) | Standard Error 9.581 |
| Sham Control, Delayed, Males, CS- | Fear-potentiated Startle Responses to the CS+ and CS- During Acquisition | 26.64 Fear-potentiated startle (microvolts) | Standard Error 8.056 |
| Stress, Immediate, Females, CS+ | Fear-potentiated Startle Responses to the CS+ and CS- During Acquisition | 64.313 Fear-potentiated startle (microvolts) | Standard Error 7.051 |
| Stress, Immediate, Females, CS- | Fear-potentiated Startle Responses to the CS+ and CS- During Acquisition | 14.437 Fear-potentiated startle (microvolts) | Standard Error 5.929 |
| Stress, Delayed, Females, CS+ | Fear-potentiated Startle Responses to the CS+ and CS- During Acquisition | 75.269 Fear-potentiated startle (microvolts) | Standard Error 7.365 |
| Stress, Delayed, Females, CS- | Fear-potentiated Startle Responses to the CS+ and CS- During Acquisition | 33.479 Fear-potentiated startle (microvolts) | Standard Error 6.193 |
| Sham Control, Immediate, Females, CS+ | Fear-potentiated Startle Responses to the CS+ and CS- During Acquisition | 61.243 Fear-potentiated startle (microvolts) | Standard Error 7.101 |
| Sham Control, Immediate, Females, CS- | Fear-potentiated Startle Responses to the CS+ and CS- During Acquisition | 26.584 Fear-potentiated startle (microvolts) | Standard Error 5.971 |
| Sham Control, Delayed, Females, CS+ | Fear-potentiated Startle Responses to the CS+ and CS- During Acquisition | 62.828 Fear-potentiated startle (microvolts) | Standard Error 7.051 |
| Sham Control, Delayed, Females, CS- | Fear-potentiated Startle Responses to the CS+ and CS- During Acquisition | 21.856 Fear-potentiated startle (microvolts) | Standard Error 5.929 |
p-value: 0.453ANOVA
Primary
Skin Conductance Responses to CS+ and CS- During Acquisition
Electrodermal activity was measured following presentation of the CS+ and CS- during acquisition on Day 1. Participants were exposed to 16 blocks of trials, with each block including a single presentation of each stimulus. During the last 12 blocks, CS+ trials included the presentation of an aversive US. For each block, skin conductance responses were quantified by calculating the average increase in electrodermal activity (from a 1 s pre-stimulus baseline) 3-6 s after CS+ or CS- onset. Average skin conductance responses to the CS+ and CS- during the last 4 blocks of trials were used as an indicator of fear learning (greater responses to the CS+, relative to the CS-, indicated greater learning).
Time frame: Average of the responses from trial block 13, trial block 14, trial block 15, and trial block 16 on Day 1
Population: The overall number of participants analyzed is not consistent with the numbers in the participant flow module. Some skin conductance responses were unable to be obtained from participants due to technical issues (e.g., poor electrode conductance).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Stress, Immediate, Males, CS+ | Skin Conductance Responses to CS+ and CS- During Acquisition | .107 Skin conductance response (μSiemens) | Standard Error 0.042 |
| Stress, Immediate, Males, CS- | Skin Conductance Responses to CS+ and CS- During Acquisition | .070 Skin conductance response (μSiemens) | Standard Error 0.039 |
| Stress, Delayed, Males, CS+ | Skin Conductance Responses to CS+ and CS- During Acquisition | .138 Skin conductance response (μSiemens) | Standard Error 0.041 |
| Stress, Delayed, Males, CS- | Skin Conductance Responses to CS+ and CS- During Acquisition | .090 Skin conductance response (μSiemens) | Standard Error 0.038 |
| Sham Control, Immediate, Males, CS+ | Skin Conductance Responses to CS+ and CS- During Acquisition | .112 Skin conductance response (μSiemens) | Standard Error 0.043 |
| Sham Control, Immediate, Males, CS- | Skin Conductance Responses to CS+ and CS- During Acquisition | .102 Skin conductance response (μSiemens) | Standard Error 0.04 |
| Sham Control, Delayed, Males, CS+ | Skin Conductance Responses to CS+ and CS- During Acquisition | .163 Skin conductance response (μSiemens) | Standard Error 0.042 |
| Sham Control, Delayed, Males, CS- | Skin Conductance Responses to CS+ and CS- During Acquisition | .105 Skin conductance response (μSiemens) | Standard Error 0.039 |
| Stress, Immediate, Females, CS+ | Skin Conductance Responses to CS+ and CS- During Acquisition | .153 Skin conductance response (μSiemens) | Standard Error 0.031 |
| Stress, Immediate, Females, CS- | Skin Conductance Responses to CS+ and CS- During Acquisition | .084 Skin conductance response (μSiemens) | Standard Error 0.029 |
| Stress, Delayed, Females, CS+ | Skin Conductance Responses to CS+ and CS- During Acquisition | .135 Skin conductance response (μSiemens) | Standard Error 0.034 |
| Stress, Delayed, Females, CS- | Skin Conductance Responses to CS+ and CS- During Acquisition | .078 Skin conductance response (μSiemens) | Standard Error 0.032 |
| Sham Control, Immediate, Females, CS+ | Skin Conductance Responses to CS+ and CS- During Acquisition | .206 Skin conductance response (μSiemens) | Standard Error 0.031 |
| Sham Control, Immediate, Females, CS- | Skin Conductance Responses to CS+ and CS- During Acquisition | .072 Skin conductance response (μSiemens) | Standard Error 0.028 |
| Sham Control, Delayed, Females, CS+ | Skin Conductance Responses to CS+ and CS- During Acquisition | .244 Skin conductance response (μSiemens) | Standard Error 0.03 |
| Sham Control, Delayed, Females, CS- | Skin Conductance Responses to CS+ and CS- During Acquisition | .096 Skin conductance response (μSiemens) | Standard Error 0.028 |
p-value: 0.923ANOVA
Primary
Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing
Electrodermal activity was measured following presentation of the CS+, 7 generalization stimuli (GSs), and CS- during generalization testing on Day 2. Participants were exposed to 3 blocks of trials, with each block including a single presentation of each stimulus. For each block, skin conductance responses were quantified by calculating the average increase in electrodermal activity (from a 1 s pre-stimulus baseline) 3-6 s after onset of the CS+, 7 GSs, or CS- onset.. Average skin conductance responses to each stimulus across all 3 blocks were used as an indicator of fear expression. Greater scores for the generalization stimuli (GS) indicated a greater generalization of fear.
Time frame: Average of responses from all trials on Day 2
Population: The overall number of participants analyzed is not consistent with the numbers in the participant flow module. Some skin conductance responses were unable to be obtained from participants due to technical issues (e.g., poor electrode conductance).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Stress, Immediate, Males, CS+ | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .193 Skin conductance response (μSiemens) | Standard Error 0.049 |
| Stress, Immediate, Males, CS- | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .156 Skin conductance response (μSiemens) | Standard Error 0.047 |
| Stress, Delayed, Males, CS+ | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .103 Skin conductance response (μSiemens) | Standard Error 0.039 |
| Stress, Delayed, Males, CS- | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .114 Skin conductance response (μSiemens) | Standard Error 0.043 |
| Sham Control, Immediate, Males, CS+ | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .072 Skin conductance response (μSiemens) | Standard Error 0.039 |
| Sham Control, Immediate, Males, CS- | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .046 Skin conductance response (μSiemens) | Standard Error 0.04 |
| Sham Control, Delayed, Males, CS+ | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .241 Skin conductance response (μSiemens) | Standard Error 0.053 |
| Sham Control, Delayed, Males, CS- | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .246 Skin conductance response (μSiemens) | Standard Error 0.049 |
| Stress, Immediate, Females, CS+ | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .094 Skin conductance response (μSiemens) | Standard Error 0.039 |
| Stress, Immediate, Females, CS- | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .270 Skin conductance response (μSiemens) | Standard Error 0.047 |
| Stress, Delayed, Females, CS+ | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .262 Skin conductance response (μSiemens) | Standard Error 0.045 |
| Stress, Delayed, Females, CS- | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .140 Skin conductance response (μSiemens) | Standard Error 0.037 |
| Sham Control, Immediate, Females, CS+ | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .177 Skin conductance response (μSiemens) | Standard Error 0.041 |
| Sham Control, Immediate, Females, CS- | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .095 Skin conductance response (μSiemens) | Standard Error 0.037 |
| Sham Control, Delayed, Females, CS+ | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .118 Skin conductance response (μSiemens) | Standard Error 0.038 |
| Sham Control, Delayed, Females, CS- | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .254 Skin conductance response (μSiemens) | Standard Error 0.05 |
| Stress, Delayed, Males, GS7 | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .101 Skin conductance response (μSiemens) | Standard Error 0.047 |
| Stress, Delayed, Males, CS- | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .116 Skin conductance response (μSiemens) | Standard Error 0.037 |
| Sham Control, Immediate, Males, CS+ | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .127 Skin conductance response (μSiemens) | Standard Error 0.054 |
| Sham Control, Immediate, Males, GS1 | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .154 Skin conductance response (μSiemens) | Standard Error 0.051 |
| Sham Control, Immediate, Males, GS2 | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .081 Skin conductance response (μSiemens) | Standard Error 0.043 |
| Sham Control, Immediate, Males, GS3 | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .158 Skin conductance response (μSiemens) | Standard Error 0.047 |
| Sham Control, Immediate, Males, GS4 | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .041 Skin conductance response (μSiemens) | Standard Error 0.042 |
| Sham Control, Immediate, Males, GS5 | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .053 Skin conductance response (μSiemens) | Standard Error 0.044 |
| Sham Control, Immediate, Males, GS6 | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .260 Skin conductance response (μSiemens) | Standard Error 0.058 |
| Sham Control, Immediate, Males, GS7 | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .103 Skin conductance response (μSiemens) | Standard Error 0.054 |
| Sham Control, Immediate, Males, CS- | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .138 Skin conductance response (μSiemens) | Standard Error 0.042 |
| Sham Control, Delayed, Males, CS+ | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .196 Skin conductance response (μSiemens) | Standard Error 0.048 |
| Sham Control, Delayed, Males, GS1 | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .212 Skin conductance response (μSiemens) | Standard Error 0.045 |
| Sham Control, Delayed, Males, GS2 | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .107 Skin conductance response (μSiemens) | Standard Error 0.038 |
| Sham Control, Delayed, Males, GS3 | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .129 Skin conductance response (μSiemens) | Standard Error 0.041 |
| Sham Control, Delayed, Males, GS4 | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .067 Skin conductance response (μSiemens) | Standard Error 0.037 |
| Sham Control, Delayed, Males, GS5 | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .035 Skin conductance response (μSiemens) | Standard Error 0.039 |
| Sham Control, Delayed, Males, GS6 | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .218 Skin conductance response (μSiemens) | Standard Error 0.051 |
| Sham Control, Delayed, Males, GS7 | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .193 Skin conductance response (μSiemens) | Standard Error 0.047 |
| Sham Control, Delayed, Males, CS- | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .075 Skin conductance response (μSiemens) | Standard Error 0.037 |
| Stress, Immediate, Females, CS+ | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .225 Skin conductance response (μSiemens) | Standard Error 0.036 |
| Stress, Immediate, Females, GS1 | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .184 Skin conductance response (μSiemens) | Standard Error 0.035 |
| Stress, Immediate, Females, GS2 | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .119 Skin conductance response (μSiemens) | Standard Error 0.029 |
| Stress, Immediate, Females, GS3 | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .168 Skin conductance response (μSiemens) | Standard Error 0.032 |
| Stress, Immediate, Females, GS4 | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .123 Skin conductance response (μSiemens) | Standard Error 0.029 |
| Stress, Immediate, Females, GS5 | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .132 Skin conductance response (μSiemens) | Standard Error 0.03 |
| Stress, Immediate, Females, GS6 | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .232 Skin conductance response (μSiemens) | Standard Error 0.039 |
| Stress, Immediate, Females, GS7 | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .196 Skin conductance response (μSiemens) | Standard Error 0.036 |
| Stress, Immediate, Females, CS- | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .093 Skin conductance response (μSiemens) | Standard Error 0.028 |
| Stress, Delayed, Females, CS+ | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .213 Skin conductance response (μSiemens) | Standard Error 0.04 |
| Stress, Delayed, Females, GS1 | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .201 Skin conductance response (μSiemens) | Standard Error 0.038 |
| Stress, Delayed, Females, GS2 | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .098 Skin conductance response (μSiemens) | Standard Error 0.032 |
| Stress, Delayed, Females, GS3 | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .147 Skin conductance response (μSiemens) | Standard Error 0.035 |
| Stress, Delayed, Females, GS4 | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .085 Skin conductance response (μSiemens) | Standard Error 0.031 |
| Stress, Delayed, Females, GS5 | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .122 Skin conductance response (μSiemens) | Standard Error 0.033 |
| Stress, Delayed, Females, GS6 | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .252 Skin conductance response (μSiemens) | Standard Error 0.043 |
| Stress, Delayed, Females, GS7 | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .127 Skin conductance response (μSiemens) | Standard Error 0.04 |
| Stress, Delayed, Females, CS- | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .074 Skin conductance response (μSiemens) | Standard Error 0.031 |
| Sham Control, Immediate, Females, CS+ | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .226 Skin conductance response (μSiemens) | Standard Error 0.037 |
| Sham Control, Immediate, Females, GS1 | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .199 Skin conductance response (μSiemens) | Standard Error 0.035 |
| Sham Control, Immediate, Females, GS2 | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .094 Skin conductance response (μSiemens) | Standard Error 0.029 |
| Sham Control, Immediate, Females, GS3 | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .150 Skin conductance response (μSiemens) | Standard Error 0.032 |
| Sham Control, Immediate, Females, GS4 | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .100 Skin conductance response (μSiemens) | Standard Error 0.029 |
| Sham Control, Immediate, Females, GS5 | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .097 Skin conductance response (μSiemens) | Standard Error 0.03 |
| Sham Control, Immediate, Females, GS6 | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .259 Skin conductance response (μSiemens) | Standard Error 0.039 |
| Sham Control, Immediate, Females, GS7 | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .137 Skin conductance response (μSiemens) | Standard Error 0.037 |
| Sham Control, Immediate, Females, CS- | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .109 Skin conductance response (μSiemens) | Standard Error 0.029 |
| Sham Control, Delayed, Females, CS+ | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .243 Skin conductance response (μSiemens) | Standard Error 0.035 |
| Sham Control, Delayed, Females, GS1 | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .261 Skin conductance response (μSiemens) | Standard Error 0.033 |
| Sham Control, Delayed, Females, GS2 | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .100 Skin conductance response (μSiemens) | Standard Error 0.028 |
| Sham Control, Delayed, Females, GS3 | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .195 Skin conductance response (μSiemens) | Standard Error 0.03 |
| Sham Control, Delayed, Females, GS4 | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .113 Skin conductance response (μSiemens) | Standard Error 0.027 |
| Sham Control, Delayed, Females, GS5 | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .138 Skin conductance response (μSiemens) | Standard Error 0.028 |
| Sham Control, Delayed, Females, GS6 | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .326 Skin conductance response (μSiemens) | Standard Error 0.037 |
| Sham Control, Delayed, Females, GS7 | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .198 Skin conductance response (μSiemens) | Standard Error 0.035 |
| Sham Control, Delayed, Females, CS- | Skin Conductance Responses to CS+, Generalization Stimuli, and CS- During Generalization Testing | .158 Skin conductance response (μSiemens) | Standard Error 0.027 |
p-value: 0.399ANOVA
Primary
US Expectancy Ratings to CS+ and CS- During Acquisition
Participants were exposed to 16 blocks of trials, and each block included 1 presentation of the CS+ and one presentation of the CS-. During the last 12 blocks, CS+ trials included the presentation of an aversive US. During each trial, participants pressed, within 3 seconds of stimulus onset, a button marked + if they expected the stimulus to be followed by the US, a button marked - if they did not expect the stimulus to be followed by the US, or a button marked 0 if they were uncertain. For the purpose of data analysis, + was scored as +1, - were scored as -1, and 0 was scored as 0. Average expectancy ratings during the last 4 blocks of trials were used as an indicator of fear learning (greater responses to the CS+, relative to the CS-, indicated greater learning).
Time frame: Average of the ratings from trial block 13, trial block 14, trial block 15, and trial block 16 on Day 1
Population: The overall number of participants analyzed is not consistent with the numbers in the participant flow module. Some US expectancy ratings were unable to be obtained from participants due to technical issues (e.g., response pad malfunction) or participant error.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Stress, Immediate, Males, CS+ | US Expectancy Ratings to CS+ and CS- During Acquisition | .737 score on scale from -1 to +1 | Standard Error 0.064 |
| Stress, Immediate, Males, CS- | US Expectancy Ratings to CS+ and CS- During Acquisition | -.865 score on scale from -1 to +1 | Standard Error 0.068 |
| Stress, Delayed, Males, CS+ | US Expectancy Ratings to CS+ and CS- During Acquisition | .964 score on scale from -1 to +1 | Standard Error 0.062 |
| Stress, Delayed, Males, CS- | US Expectancy Ratings to CS+ and CS- During Acquisition | -.954 score on scale from -1 to +1 | Standard Error 0.066 |
| Sham Control, Immediate, Males, CS+ | US Expectancy Ratings to CS+ and CS- During Acquisition | .797 score on scale from -1 to +1 | Standard Error 0.066 |
| Sham Control, Immediate, Males, CS- | US Expectancy Ratings to CS+ and CS- During Acquisition | -.775 score on scale from -1 to +1 | Standard Error 0.07 |
| Sham Control, Delayed, Males, CS+ | US Expectancy Ratings to CS+ and CS- During Acquisition | .860 score on scale from -1 to +1 | Standard Error 0.061 |
| Sham Control, Delayed, Males, CS- | US Expectancy Ratings to CS+ and CS- During Acquisition | -.907 score on scale from -1 to +1 | Standard Error 0.065 |
| Stress, Immediate, Females, CS+ | US Expectancy Ratings to CS+ and CS- During Acquisition | .807 score on scale from -1 to +1 | Standard Error 0.047 |
| Stress, Immediate, Females, CS- | US Expectancy Ratings to CS+ and CS- During Acquisition | -.782 score on scale from -1 to +1 | Standard Error 0.05 |
| Stress, Delayed, Females, CS+ | US Expectancy Ratings to CS+ and CS- During Acquisition | .867 score on scale from -1 to +1 | Standard Error 0.05 |
| Stress, Delayed, Females, CS- | US Expectancy Ratings to CS+ and CS- During Acquisition | -.845 score on scale from -1 to +1 | Standard Error 0.053 |
| Sham Control, Immediate, Females, CS+ | US Expectancy Ratings to CS+ and CS- During Acquisition | .889 score on scale from -1 to +1 | Standard Error 0.047 |
| Sham Control, Immediate, Females, CS- | US Expectancy Ratings to CS+ and CS- During Acquisition | -.840 score on scale from -1 to +1 | Standard Error 0.05 |
| Sham Control, Delayed, Females, CS+ | US Expectancy Ratings to CS+ and CS- During Acquisition | .881 score on scale from -1 to +1 | Standard Error 0.047 |
| Sham Control, Delayed, Females, CS- | US Expectancy Ratings to CS+ and CS- During Acquisition | -.898 score on scale from -1 to +1 | Standard Error 0.05 |
p-value: 0.872ANOVA
Primary
US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing
Participants were exposed to 3 blocks of trials, and each block included 1 presentation of the CS+, one presentation of each of 7 generalization stimuli (GSs), and one presentation of the CS-. Participants were instructed to press, within 3 seconds of stimulus onset, a button marked + if they expected the stimulus to be followed by the US, a button marked - if they did not expect the stimulus to be followed by the US, or a button marked 0 if they were uncertain. For the purpose of data analysis, + was scored as +1, - was scored as -1, and 0 was scored as 0. Average expectancy ratings for each stimulus across all 3 blocks were used as an indicator of fear. Greater scores for the generalization stimuli (GS) indicated a greater generalization of fear.
Time frame: Average of ratings from all trials on Day 2
Population: The overall number of participants analyzed is not consistent with the numbers in the participant flow module. Some US expectancy ratings were unable to be obtained from participants due to technical issues (e.g., response pad malfunction) or participant error.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Stress, Immediate, Males, CS+ | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | .217 score on scale from -1 to +1 | Standard Error 0.119 |
| Stress, Immediate, Males, CS- | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | .140 score on scale from -1 to +1 | Standard Error 0.094 |
| Stress, Delayed, Males, CS+ | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.357 score on scale from -1 to +1 | Standard Error 0.111 |
| Stress, Delayed, Males, CS- | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.527 score on scale from -1 to +1 | Standard Error 0.095 |
| Sham Control, Immediate, Males, CS+ | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.822 score on scale from -1 to +1 | Standard Error 0.069 |
| Sham Control, Immediate, Males, CS- | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.810 score on scale from -1 to +1 | Standard Error 0.069 |
| Sham Control, Delayed, Males, CS+ | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.907 score on scale from -1 to +1 | Standard Error 0.05 |
| Sham Control, Delayed, Males, CS- | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.984 score on scale from -1 to +1 | Standard Error 0.045 |
| Stress, Immediate, Females, CS+ | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.961 score on scale from -1 to +1 | Standard Error 0.045 |
| Stress, Immediate, Females, CS- | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.089 score on scale from -1 to +1 | Standard Error 0.116 |
| Stress, Delayed, Females, CS+ | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.067 score on scale from -1 to +1 | Standard Error 0.092 |
| Stress, Delayed, Females, CS- | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.533 score on scale from -1 to +1 | Standard Error 0.109 |
| Sham Control, Immediate, Females, CS+ | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.519 score on scale from -1 to +1 | Standard Error 0.093 |
| Sham Control, Immediate, Females, CS- | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.807 score on scale from -1 to +1 | Standard Error 0.068 |
| Sham Control, Delayed, Females, CS+ | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.874 score on scale from -1 to +1 | Standard Error 0.067 |
| Sham Control, Delayed, Females, CS- | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.889 score on scale from -1 to +1 | Standard Error 0.049 |
| Stress, Delayed, Males, GS7 | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.911 score on scale from -1 to +1 | Standard Error 0.044 |
| Stress, Delayed, Males, CS- | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.948 score on scale from -1 to +1 | Standard Error 0.044 |
| Sham Control, Immediate, Males, CS+ | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | .315 score on scale from -1 to +1 | Standard Error 0.13 |
| Sham Control, Immediate, Males, GS1 | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | .204 score on scale from -1 to +1 | Standard Error 0.103 |
| Sham Control, Immediate, Males, GS2 | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.130 score on scale from -1 to +1 | Standard Error 0.121 |
| Sham Control, Immediate, Males, GS3 | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.296 score on scale from -1 to +1 | Standard Error 0.104 |
| Sham Control, Immediate, Males, GS4 | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.593 score on scale from -1 to +1 | Standard Error 0.076 |
| Sham Control, Immediate, Males, GS5 | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.676 score on scale from -1 to +1 | Standard Error 0.075 |
| Sham Control, Immediate, Males, GS6 | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.833 score on scale from -1 to +1 | Standard Error 0.055 |
| Sham Control, Immediate, Males, GS7 | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.907 score on scale from -1 to +1 | Standard Error 0.049 |
| Sham Control, Immediate, Males, CS- | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.870 score on scale from -1 to +1 | Standard Error 0.049 |
| Sham Control, Delayed, Males, CS+ | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | .225 score on scale from -1 to +1 | Standard Error 0.119 |
| Sham Control, Delayed, Males, GS1 | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | .016 score on scale from -1 to +1 | Standard Error 0.094 |
| Sham Control, Delayed, Males, GS2 | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.411 score on scale from -1 to +1 | Standard Error 0.111 |
| Sham Control, Delayed, Males, GS3 | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.496 score on scale from -1 to +1 | Standard Error 0.095 |
| Sham Control, Delayed, Males, GS4 | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.740 score on scale from -1 to +1 | Standard Error 0.069 |
| Sham Control, Delayed, Males, GS5 | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.814 score on scale from -1 to +1 | Standard Error 0.069 |
| Sham Control, Delayed, Males, GS6 | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.837 score on scale from -1 to +1 | Standard Error 0.05 |
| Sham Control, Delayed, Males, GS7 | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.899 score on scale from -1 to +1 | Standard Error 0.045 |
| Sham Control, Delayed, Males, CS- | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.907 score on scale from -1 to +1 | Standard Error 0.045 |
| Stress, Immediate, Females, CS+ | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | .135 score on scale from -1 to +1 | Standard Error 0.087 |
| Stress, Immediate, Females, GS1 | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | .093 score on scale from -1 to +1 | Standard Error 0.069 |
| Stress, Immediate, Females, GS2 | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.447 score on scale from -1 to +1 | Standard Error 0.082 |
| Stress, Immediate, Females, GS3 | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.489 score on scale from -1 to +1 | Standard Error 0.07 |
| Stress, Immediate, Females, GS4 | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.768 score on scale from -1 to +1 | Standard Error 0.051 |
| Stress, Immediate, Females, GS5 | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.768 score on scale from -1 to +1 | Standard Error 0.051 |
| Stress, Immediate, Females, GS6 | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.808 score on scale from -1 to +1 | Standard Error 0.037 |
| Stress, Immediate, Females, GS7 | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.865 score on scale from -1 to +1 | Standard Error 0.033 |
| Stress, Immediate, Females, CS- | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.882 score on scale from -1 to +1 | Standard Error 0.033 |
| Stress, Delayed, Females, CS+ | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.010 score on scale from -1 to +1 | Standard Error 0.096 |
| Stress, Delayed, Females, GS1 | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | .035 score on scale from -1 to +1 | Standard Error 0.076 |
| Stress, Delayed, Females, GS2 | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.384 score on scale from -1 to +1 | Standard Error 0.09 |
| Stress, Delayed, Females, GS3 | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.455 score on scale from -1 to +1 | Standard Error 0.077 |
| Stress, Delayed, Females, GS4 | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.707 score on scale from -1 to +1 | Standard Error 0.056 |
| Stress, Delayed, Females, GS5 | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.753 score on scale from -1 to +1 | Standard Error 0.056 |
| Stress, Delayed, Females, GS6 | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.818 score on scale from -1 to +1 | Standard Error 0.04 |
| Stress, Delayed, Females, GS7 | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.904 score on scale from -1 to +1 | Standard Error 0.036 |
| Stress, Delayed, Females, CS- | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.889 score on scale from -1 to +1 | Standard Error 0.036 |
| Sham Control, Immediate, Females, CS+ | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | .116 score on scale from -1 to +1 | Standard Error 0.09 |
| Sham Control, Immediate, Females, GS1 | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | .120 score on scale from -1 to +1 | Standard Error 0.071 |
| Sham Control, Immediate, Females, GS2 | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.404 score on scale from -1 to +1 | Standard Error 0.084 |
| Sham Control, Immediate, Females, GS3 | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.467 score on scale from -1 to +1 | Standard Error 0.072 |
| Sham Control, Immediate, Females, GS4 | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.769 score on scale from -1 to +1 | Standard Error 0.053 |
| Sham Control, Immediate, Females, GS5 | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.787 score on scale from -1 to +1 | Standard Error 0.052 |
| Sham Control, Immediate, Females, GS6 | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.867 score on scale from -1 to +1 | Standard Error 0.038 |
| Sham Control, Immediate, Females, GS7 | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.911 score on scale from -1 to +1 | Standard Error 0.034 |
| Sham Control, Immediate, Females, CS- | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.889 score on scale from -1 to +1 | Standard Error 0.034 |
| Sham Control, Delayed, Females, CS+ | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | .171 score on scale from -1 to +1 | Standard Error 0.087 |
| Sham Control, Delayed, Females, GS1 | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | .142 score on scale from -1 to +1 | Standard Error 0.069 |
| Sham Control, Delayed, Females, GS2 | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.383 score on scale from -1 to +1 | Standard Error 0.081 |
| Sham Control, Delayed, Females, GS3 | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.475 score on scale from -1 to +1 | Standard Error 0.07 |
| Sham Control, Delayed, Females, GS4 | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.737 score on scale from -1 to +1 | Standard Error 0.051 |
| Sham Control, Delayed, Females, GS5 | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.737 score on scale from -1 to +1 | Standard Error 0.05 |
| Sham Control, Delayed, Females, GS6 | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.871 score on scale from -1 to +1 | Standard Error 0.037 |
| Sham Control, Delayed, Females, GS7 | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.942 score on scale from -1 to +1 | Standard Error 0.033 |
| Sham Control, Delayed, Females, CS- | US Expectancy Ratings to CS+, CS-, and Generalization Stimuli During Generalization Testing | -.954 score on scale from -1 to +1 | Standard Error 0.033 |
p-value: 0.998ANOVA
Secondary
Average Subjective Pain, as Assessed by Verbal Self Report
During the stress or sham control manipulation, participants rated the painfulness of the water bath at 1-minute intervals on an 11-point scale ranging from 0-10, with 0 = lack of pain and 10 = unbearable pain. The obtained ratings were averaged and analyzed. Greater ratings indicated greater subjective pain during the stressor.
Time frame: Stress or sham control condition on Day 1
Population: The overall number of participants analyzed is not consistent with the numbers in the participant flow module. Some participants did not report subjective pain ratings.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Stress, Immediate, Males, CS+ | Average Subjective Pain, as Assessed by Verbal Self Report | 6.089 score on a scale of 0-10 | Standard Error 0.228 |
| Stress, Immediate, Males, CS- | Average Subjective Pain, as Assessed by Verbal Self Report | 6.415 score on a scale of 0-10 | Standard Error 0.223 |
| Stress, Delayed, Males, CS+ | Average Subjective Pain, as Assessed by Verbal Self Report | .123 score on a scale of 0-10 | Standard Error 0.243 |
| Stress, Delayed, Males, CS- | Average Subjective Pain, as Assessed by Verbal Self Report | .159 score on a scale of 0-10 | Standard Error 0.226 |
| Sham Control, Immediate, Males, CS+ | Average Subjective Pain, as Assessed by Verbal Self Report | 6.806 score on a scale of 0-10 | Standard Error 0.167 |
| Sham Control, Immediate, Males, CS- | Average Subjective Pain, as Assessed by Verbal Self Report | 6.765 score on a scale of 0-10 | Standard Error 0.181 |
| Sham Control, Delayed, Males, CS+ | Average Subjective Pain, as Assessed by Verbal Self Report | .092 score on a scale of 0-10 | Standard Error 0.172 |
| Sham Control, Delayed, Males, CS- | Average Subjective Pain, as Assessed by Verbal Self Report | .131 score on a scale of 0-10 | Standard Error 0.163 |
p-value: 0.519ANOVA
Secondary
Average Subjective Stress, as Assessed by Verbal Self Report
During the stress or sham control manipulation, participants rated the stressfulness of the water bath at 1-minute intervals on an 11-point scale ranging from 0-10, with 0 = lack of stress and 10 = unbearable stress. The obtained ratings were averaged and analyzed. Greater ratings indicated greater subjective stress during the stressor.
Time frame: Stress or sham control condition on Day 1
Population: The overall number of participants analyzed is not consistent with the numbers in the participant flow module. Some participants did not report subjective stress ratings.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Stress, Immediate, Males, CS+ | Average Subjective Stress, as Assessed by Verbal Self Report | 4.457 score on scale of 0-10 | Standard Error 0.289 |
| Stress, Immediate, Males, CS- | Average Subjective Stress, as Assessed by Verbal Self Report | 5.778 score on scale of 0-10 | Standard Error 0.283 |
| Stress, Delayed, Males, CS+ | Average Subjective Stress, as Assessed by Verbal Self Report | .675 score on scale of 0-10 | Standard Error 0.307 |
| Stress, Delayed, Males, CS- | Average Subjective Stress, as Assessed by Verbal Self Report | .318 score on scale of 0-10 | Standard Error 0.286 |
| Sham Control, Immediate, Males, CS+ | Average Subjective Stress, as Assessed by Verbal Self Report | 5.910 score on scale of 0-10 | Standard Error 0.212 |
| Sham Control, Immediate, Males, CS- | Average Subjective Stress, as Assessed by Verbal Self Report | 5.843 score on scale of 0-10 | Standard Error 0.23 |
| Sham Control, Delayed, Males, CS+ | Average Subjective Stress, as Assessed by Verbal Self Report | .184 score on scale of 0-10 | Standard Error 0.217 |
| Sham Control, Delayed, Males, CS- | Average Subjective Stress, as Assessed by Verbal Self Report | .405 score on scale of 0-10 | Standard Error 0.207 |
p-value: 0.007ANOVA
Secondary
Change in Baseline Salivary Alpha-amylase (U/ml)
Saliva samples were collected from participants prior to undergoing the stress or sham control condition (baseline) and then immediately after the manipulation. The change in salivary alpha-amylase levels was analyzed. Greater levels indicated greater alpha-amylase responses to stress.
Time frame: Day 1 (change from baseline to immediately after stress)
Population: The overall number of participants analyzed is not consistent with the numbers in the participant flow module. Some salivary cortisol levels were unable to be obtained due to a lack of adequate saliva.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Stress, Immediate, Males, CS+ | Change in Baseline Salivary Alpha-amylase (U/ml) | 4.210 Change in alpha-amylase (U/ml) | Standard Error 7.132 |
| Stress, Immediate, Males, CS- | Change in Baseline Salivary Alpha-amylase (U/ml) | -12.943 Change in alpha-amylase (U/ml) | Standard Error 7.042 |
| Stress, Delayed, Males, CS+ | Change in Baseline Salivary Alpha-amylase (U/ml) | 7.656 Change in alpha-amylase (U/ml) | Standard Error 7.528 |
| Stress, Delayed, Males, CS- | Change in Baseline Salivary Alpha-amylase (U/ml) | -3.411 Change in alpha-amylase (U/ml) | Standard Error 6.792 |
| Sham Control, Immediate, Males, CS+ | Change in Baseline Salivary Alpha-amylase (U/ml) | 17.561 Change in alpha-amylase (U/ml) | Standard Error 5.4 |
| Sham Control, Immediate, Males, CS- | Change in Baseline Salivary Alpha-amylase (U/ml) | 2.608 Change in alpha-amylase (U/ml) | Standard Error 6.005 |
| Sham Control, Delayed, Males, CS+ | Change in Baseline Salivary Alpha-amylase (U/ml) | 5.090 Change in alpha-amylase (U/ml) | Standard Error 5.323 |
| Sham Control, Delayed, Males, CS- | Change in Baseline Salivary Alpha-amylase (U/ml) | -3.601 Change in alpha-amylase (U/ml) | Standard Error 5.213 |
p-value: 0.992ANOVA
Secondary
Change in Baseline Salivary Cortisol (Nmol/l)
Saliva samples were collected from participants prior to undergoing the stress or sham control condition (baseline) and then 25 min later. The change in salivary cortisol levels was analyzed. Greater levels indicated greater cortisol responses to stress.
Time frame: Day 1 (change from baseline to 25 min post-stress)
Population: The overall number of participants analyzed is not consistent with the numbers in the participant flow module. Some salivary cortisol levels were unable to be obtained due to a lack of adequate saliva.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Stress, Immediate, Males, CS+ | Change in Baseline Salivary Cortisol (Nmol/l) | 1.413 Change in cortisol (nmol/l) | Standard Error 0.308 |
| Stress, Immediate, Males, CS- | Change in Baseline Salivary Cortisol (Nmol/l) | 1.014 Change in cortisol (nmol/l) | Standard Error 0.315 |
| Stress, Delayed, Males, CS+ | Change in Baseline Salivary Cortisol (Nmol/l) | -.039 Change in cortisol (nmol/l) | Standard Error 0.333 |
| Stress, Delayed, Males, CS- | Change in Baseline Salivary Cortisol (Nmol/l) | .236 Change in cortisol (nmol/l) | Standard Error 0.32 |
| Sham Control, Immediate, Males, CS+ | Change in Baseline Salivary Cortisol (Nmol/l) | .728 Change in cortisol (nmol/l) | Standard Error 0.227 |
| Sham Control, Immediate, Males, CS- | Change in Baseline Salivary Cortisol (Nmol/l) | .710 Change in cortisol (nmol/l) | Standard Error 0.254 |
| Sham Control, Delayed, Males, CS+ | Change in Baseline Salivary Cortisol (Nmol/l) | .558 Change in cortisol (nmol/l) | Standard Error 0.231 |
| Sham Control, Delayed, Males, CS- | Change in Baseline Salivary Cortisol (Nmol/l) | -.091 Change in cortisol (nmol/l) | Standard Error 0.223 |
p-value: 0.1ANOVA
Secondary
Change in Heart Rate (Bpm)
Heart rate (bpm) measurements were aken via the PPG module of the Biopac MP150 system from participants prior to undergoing the stress or sham control condition (baseline) and then halfway through the manipulation.The change in heart rate was analyzed.
Time frame: Day 1 (change from baseline to during stress or sham control manipulation)
Population: The overall number of participants analyzed is not consistent with the numbers in the participant flow module. Some heart rate measurements were unable to be obtained from participants due to technical issues (e.g., pulse oximeter malfunction).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Stress, Immediate, Males, CS+ | Change in Heart Rate (Bpm) | 4.924 Change in heart rate (beats per minute) | Standard Error 1.159 |
| Stress, Immediate, Males, CS- | Change in Heart Rate (Bpm) | 3.922 Change in heart rate (beats per minute) | Standard Error 1.12 |
| Stress, Delayed, Males, CS+ | Change in Heart Rate (Bpm) | -.379 Change in heart rate (beats per minute) | Standard Error 1.235 |
| Stress, Delayed, Males, CS- | Change in Heart Rate (Bpm) | .345 Change in heart rate (beats per minute) | Standard Error 1.146 |
| Sham Control, Immediate, Males, CS+ | Change in Heart Rate (Bpm) | 5.339 Change in heart rate (beats per minute) | Standard Error 0.851 |
| Sham Control, Immediate, Males, CS- | Change in Heart Rate (Bpm) | 4.348 Change in heart rate (beats per minute) | Standard Error 0.918 |
| Sham Control, Delayed, Males, CS+ | Change in Heart Rate (Bpm) | .096 Change in heart rate (beats per minute) | Standard Error 0.873 |
| Sham Control, Delayed, Males, CS- | Change in Heart Rate (Bpm) | -1.337 Change in heart rate (beats per minute) | Standard Error 0.835 |
p-value: 0.457ANOVA
Secondary
Change in Salivary Progesterone (pg/ml)
Saliva samples were collected from female participants prior to undergoing the stress or sham control condition (baseline) and then 25 min later. The change in salivary progesterone levels were analyzed.
Time frame: Day 1 (change from baseline to 25 min post-stress)
Population: The overall number of participants analyzed is not consistent with the numbers in the participant flow module. Some salivary cortisol levels were unable to be obtained due to a lack of adequate saliva.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Stress, Immediate, Males, CS+ | Change in Salivary Progesterone (pg/ml) | 247.165 Change in progesterone (pg/ml) | Standard Error 51.177 |
| Stress, Immediate, Males, CS- | Change in Salivary Progesterone (pg/ml) | 160.933 Change in progesterone (pg/ml) | Standard Error 56.776 |
| Stress, Delayed, Males, CS+ | Change in Salivary Progesterone (pg/ml) | 197.625 Change in progesterone (pg/ml) | Standard Error 52.856 |
| Stress, Delayed, Males, CS- | Change in Salivary Progesterone (pg/ml) | 198.469 Change in progesterone (pg/ml) | Standard Error 52.421 |
p-value: 0.415ANOVA
Other Pre-specified
Anxiety Sensitivity Index
The Anxiety Sensitivity Index (ASI) was administered following generalization testing on Day 2. The ASI consists of 18 items and yields a score that reflects an individual's dispositional anxiety sensitivity. The minimum score is 0, and the maximum score is 72. Greater scores reflect a greater sensitivity to anxiety.
Time frame: Day 2 - following generalization testing
Population: The overall number of participants analyzed is not consistent with the numbers in the participant flow module. Some participants did not complete the questionnaire.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Stress, Immediate, Males, CS+ | Anxiety Sensitivity Index | 16.047 score on a scale of 0-72 | Standard Error 1.649 |
| Stress, Immediate, Males, CS- | Anxiety Sensitivity Index | 15.933 score on a scale of 0-72 | Standard Error 1.612 |
| Stress, Delayed, Males, CS+ | Anxiety Sensitivity Index | 14.816 score on a scale of 0-72 | Standard Error 1.754 |
| Stress, Delayed, Males, CS- | Anxiety Sensitivity Index | 14.591 score on a scale of 0-72 | Standard Error 1.63 |
| Sham Control, Immediate, Males, CS+ | Anxiety Sensitivity Index | 18.838 score on a scale of 0-72 | Standard Error 1.209 |
| Sham Control, Immediate, Males, CS- | Anxiety Sensitivity Index | 16.882 score on a scale of 0-72 | Standard Error 1.311 |
| Sham Control, Delayed, Males, CS+ | Anxiety Sensitivity Index | 17.171 score on a scale of 0-72 | Standard Error 1.24 |
| Sham Control, Delayed, Males, CS- | Anxiety Sensitivity Index | 15.619 score on a scale of 0-72 | Standard Error 1.18 |
p-value: 0.901ANOVA
Other Pre-specified
Center for Epidemiological Studies Depression Scale (CES-D)
The Center for Epidemiological Studies Depression Scale (CES-D) was administered following generalization testing on Day 2. The CES-D is a 20-item measure of symptoms of depression. The possible range for scores is 0-60 with higher scores suggesting more severe symptoms of depression.
Time frame: Day 2 - following generalization testing
Population: The overall number of participants analyzed is not consistent with the numbers in the participant flow module. Some participants did not complete the questionnaire.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Stress, Immediate, Males, CS+ | Center for Epidemiological Studies Depression Scale (CES-D) | 12.767 score of a scale of 0-60 | Standard Error 1.439 |
| Stress, Immediate, Males, CS- | Center for Epidemiological Studies Depression Scale (CES-D) | 10.000 score of a scale of 0-60 | Standard Error 1.407 |
| Stress, Delayed, Males, CS+ | Center for Epidemiological Studies Depression Scale (CES-D) | 15.579 score of a scale of 0-60 | Standard Error 1.531 |
| Stress, Delayed, Males, CS- | Center for Epidemiological Studies Depression Scale (CES-D) | 10.909 score of a scale of 0-60 | Standard Error 1.423 |
| Sham Control, Immediate, Males, CS+ | Center for Epidemiological Studies Depression Scale (CES-D) | 15.950 score of a scale of 0-60 | Standard Error 1.055 |
| Sham Control, Immediate, Males, CS- | Center for Epidemiological Studies Depression Scale (CES-D) | 13.441 score of a scale of 0-60 | Standard Error 1.144 |
| Sham Control, Delayed, Males, CS+ | Center for Epidemiological Studies Depression Scale (CES-D) | 13.974 score of a scale of 0-60 | Standard Error 1.082 |
| Sham Control, Delayed, Males, CS- | Center for Epidemiological Studies Depression Scale (CES-D) | 14.583 score of a scale of 0-60 | Standard Error 1.03 |
p-value: 0.166ANOVA
Other Pre-specified
Childhood Trauma Questionnaire (CTQ)
The Childhood Trauma Questionnaire (CTQ) was administered following generalization testing on Day 2. The questionnaire consists of 25 items and yields a score between 25 and 125. Higher scores represent greater levels of childhood trauma exposure.
Time frame: Day 2 - following generalization testing
Population: The overall number of participants analyzed is not consistent with the numbers in the participant flow module. Some participants did not complete the questionnaire.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Stress, Immediate, Males, CS+ | Childhood Trauma Questionnaire (CTQ) | 34.93 score on a scale of 25-125 | Standard Error 1.836 |
| Stress, Immediate, Males, CS- | Childhood Trauma Questionnaire (CTQ) | 32.600 score on a scale of 25-125 | Standard Error 1.795 |
| Stress, Delayed, Males, CS+ | Childhood Trauma Questionnaire (CTQ) | 31.632 score on a scale of 25-125 | Standard Error 1.953 |
| Stress, Delayed, Males, CS- | Childhood Trauma Questionnaire (CTQ) | 34.909 score on a scale of 25-125 | Standard Error 1.815 |
| Sham Control, Immediate, Males, CS+ | Childhood Trauma Questionnaire (CTQ) | 37.688 score on a scale of 25-125 | Standard Error 1.346 |
| Sham Control, Immediate, Males, CS- | Childhood Trauma Questionnaire (CTQ) | 34.471 score on a scale of 25-125 | Standard Error 1.46 |
| Sham Control, Delayed, Males, CS+ | Childhood Trauma Questionnaire (CTQ) | 35.184 score on a scale of 25-125 | Standard Error 1.381 |
| Sham Control, Delayed, Males, CS- | Childhood Trauma Questionnaire (CTQ) | 35.333 score on a scale of 25-125 | Standard Error 1.314 |
p-value: 0.627ANOVA
Other Pre-specified
PTSD Checklist - Civilian Version
The PTSD Checklist - Civilian Version was administered following generalization testing on Day 2. The checklist is a 17-item measure of symptoms of post-traumatic stress disorder (PTSD). The minimum score is 0, and the maximum score is 80. Greater scores reflect greater symptoms related to PTSD.
Time frame: Day 2 - following generalization testing
Population: The overall number of participants analyzed is not consistent with the numbers in the participant flow module. Some participants did not complete the questionnaire.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Stress, Immediate, Males, CS+ | PTSD Checklist - Civilian Version | 31.628 score on a scale of 0-80 | Standard Error 1.774 |
| Stress, Immediate, Males, CS- | PTSD Checklist - Civilian Version | 29.800 score on a scale of 0-80 | Standard Error 1.734 |
| Stress, Delayed, Males, CS+ | PTSD Checklist - Civilian Version | 34.868 score on a scale of 0-80 | Standard Error 1.887 |
| Stress, Delayed, Males, CS- | PTSD Checklist - Civilian Version | 30.886 score on a scale of 0-80 | Standard Error 1.754 |
| Sham Control, Immediate, Males, CS+ | PTSD Checklist - Civilian Version | 36.088 score on a scale of 0-80 | Standard Error 1.301 |
| Sham Control, Immediate, Males, CS- | PTSD Checklist - Civilian Version | 32.456 score on a scale of 0-80 | Standard Error 1.411 |
| Sham Control, Delayed, Males, CS+ | PTSD Checklist - Civilian Version | 34.868 score on a scale of 0-80 | Standard Error 1.335 |
| Sham Control, Delayed, Males, CS- | PTSD Checklist - Civilian Version | 34.190 score on a scale of 0-80 | Standard Error 1.269 |
p-value: 0.252ANOVA
Other Pre-specified
Salivary Estradiol (pg/ml)
Salivary estradiol (pg/ml) was measured by enzyme immunoassay (Salimetrics LLC) performed on saliva samples collected from female participants on Days 1 and 2.
Time frame: Average across Day 1 (baseline) and Day 2 (baseline)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Stress, Immediate, Males, CS+ | Salivary Estradiol (pg/ml) | 2.040 pg/ml | Standard Error 0.131 |
| Stress, Immediate, Males, CS- | Salivary Estradiol (pg/ml) | 2.050 pg/ml | Standard Error 0.144 |
| Stress, Delayed, Males, CS+ | Salivary Estradiol (pg/ml) | 1.971 pg/ml | Standard Error 0.137 |
| Stress, Delayed, Males, CS- | Salivary Estradiol (pg/ml) | 1.955 pg/ml | Standard Error 0.132 |
p-value: 0.923ANOVA
Other Pre-specified
State Anxiety
The Spielberger State-Trait Anxiety Inventory (STAI) was administered following generalization testing on Day 2. The STAI provides scores (20-80) for state and trait anxiety. State anxiety was used for this measure and was a sum of 20 items from the STAI. The minimum score for state anxiety was 20, and the maximum score was 80. Higher scores represented higher levels of state anxiety.
Time frame: Day 2 - following generalization testing
Population: The overall number of participants analyzed is not consistent with the numbers in the participant flow module. Some participants did not complete the questionnaire.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Stress, Immediate, Males, CS+ | State Anxiety | 38.395 score on a scale of 20-80 | Standard Error 1.738 |
| Stress, Immediate, Males, CS- | State Anxiety | 36.422 score on a scale of 20-80 | Standard Error 1.699 |
| Stress, Delayed, Males, CS+ | State Anxiety | 37.868 score on a scale of 20-80 | Standard Error 1.849 |
| Stress, Delayed, Males, CS- | State Anxiety | 38.750 score on a scale of 20-80 | Standard Error 1.718 |
| Sham Control, Immediate, Males, CS+ | State Anxiety | 43.213 score on a scale of 20-80 | Standard Error 1.274 |
| Sham Control, Immediate, Males, CS- | State Anxiety | 41.441 score on a scale of 20-80 | Standard Error 1.382 |
| Sham Control, Delayed, Males, CS+ | State Anxiety | 40.868 score on a scale of 20-80 | Standard Error 1.307 |
| Sham Control, Delayed, Males, CS- | State Anxiety | 41.845 score on a scale of 20-80 | Standard Error 1.244 |
p-value: 0.981ANOVA