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Biological Response to Brief Psychological Challenge

Transduction of Psychological Stress Into Systematic Inflammation by Mitochondrial DNA Signaling

Status
Completed
Phases
NA
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT04078035
Enrollment
72
Registered
2019-09-04
Start date
2020-07-23
Completion date
2022-01-31
Last updated
2024-03-01

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Acute Inflammatory Response to Psychological Stress

Brief summary

The investigators plan to conduct a crossover experimental trial examining physiological responses to a socio-evaluative speech task under laboratory conditions. Participants will attend two laboratory sessions. At one session participants will take part in a brief laboratory stress task and at the other participants will rest for the same period. Measures of cardiovascular response will be assessed at both sessions. In addition, blood will be drawn at multiple time points across a 125 minute period to assess changes in circulating levels of cortisol, catecholamines, markers of inflammation and cell free mitochondrial DNA in response to the task. The investigators expect that the stress task will induce a specific increase in ccf-mtDNA, which will statistically mediate subsequent peak circulating Interleukin-6 and Tumor Necrosis Factor-α levels. In secondary analyses, the investigators will examine whether stress-induced increases in circulating cortisol, epinephrine, and norepinephrine levels correlate with increases in ccf-mtDNA. These studies will establish the kinetics and magnitude of psychological stress-induced ccf-mtDNA release, the association with early stress mediators, and whether ccf-mtDNA mediates the inflammatory response to acute stress in humans.

Detailed description

The proposed study will examine physiologic responses to acute psychological challenge in the laboratory among healthy adults. It is widely accepted that there is an increase in circulating markers of inflammation following a single bout of laboratory stress. This increase in systemic inflammation is believed to contribute to the damaging health effect of psychological stress. However, to date, the biological mechanisms by which psychological stress is transduced into inflammation are unclear. The investigators' preliminary evidence suggests that mitochondrion may play a role, with stress-induced increases in circulating levels of mitochondria- derived signaling molecules that are known to modulate immune cell function and the production of pro-inflammatory cytokines. To test this possibility, the investigators plan to conduct a crossover experimental trial examining physiological responses to an evaluative speech task under laboratory conditions. The investigators have previously used this task to induce physiological arousal. The investigators plan to recruit 60 non-smoking volunteers (50% female, aged 20-50 years) and test these participants on two occasions separated by at least a month. On one occasion the participants will be exposed to the speech task. On the other occasion, the participants will rest quietly for the same period. Conditions will be counterbalanced. At both visits cardiovascular responses (heart rate, blood pressure, and heart rate variability) will be assessed as measures of autonomic activation before, during and after the task period. Participants will also have an intravenous catheter inserted and blood drawn at ten time points over the two hour testing period on each occasion. Blood samples will be sent to laboratories at the University of Pittsburgh and at Columbia University for the assessment of mitochondria-derived signalling molecules, inflammatory markers, and cortisol levels.

Interventions

BEHAVIORALSocio-evaluative speech task

5-minute speech task designed to induce physiological arousal in a laboratory setting.

BEHAVIORALControl, Quiet Rest

5-minute quiet rest period.

Sponsors

National Institute of Mental Health (NIMH)
CollaboratorNIH
University of Pittsburgh
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Outcomes Assessor)

Masking description

Samples of plasma and serum will be identified by participant identification number only. Technicians assessing levels of biological measures in these samples will be blind to condition.

Intervention model description

The investigators propose a crossover experimental trial examining physiological responses to a socio-evaluative speech task under laboratory conditions. Participants will be tested on two occasions separated by at least 1 month. On one occasion, participants will be exposed to the speech task. On the other occasion, participants will rest quietly for the same period of time with identical assessment in the absence of the stressor. Conditions will be counterbalanced in randomized starting order across subjects.

Eligibility

Sex/Gender
ALL
Age
20 Years to 50 Years
Healthy volunteers
Yes

Inclusion criteria

* Generally healthy * Non-smokers/illicit drug users * Blood pressure below 140/90 * Weight \> 110 lbs * BMI \< 30 * Fluent in English * Women -- regular menstrual cycles over the past 12 months (defined as 21- 35 days in length) * Able and willing to give informed consent * Willing to abstain from alcohol and vigorous exercise for 24 hours, from food and drinks (other than water) for 3 hours and from non-prescription medications (other than oral contraception) for 2 days before testing. * Willing to attend two laboratory stress testing sessions, give blood though an intravenous catheter, undergo medical evaluation and complete psychosocial questionnaires.

Exclusion criteria

* Reported history of chronic systemic immune, metabolic or mitochondrial diseases, or chronic diseases that influence the central nervous, autonomic nervous or neuroendocrine systems, e.g., autoimmune disease, chronic infections, cardiovascular disease, diabetes, chronic kidney or liver disease, cancer treatment. * Reported psychiatric history of schizophrenia or other psychotic illness, or mood disorder. * Resting blood pressure \> 140/90 mmHg at baseline testing. * Weight \< 110 lbs * BMI equal to or greater than 30 * Report currently taking glucocorticoid, anti-inflammatory, anti-retroviral, immunosuppressant, insulin, antiarrhythmic, antihypertensive, oral hypoglycemic, antidepressant, benzodiazepine or prescription weight loss medications or other medications known to influence the immune, autonomic or neuroendocrine systems. * For women - Post-menopausal or irregular menstrual cycles over the past 12 months. Report current pregnancy or lactation. * Current smokers (defined as having smoked a cigarette in the previous 3 months). * Current illicit drug use (defined as reported use of illicit drugs such as marijuana, cocaine or heroin in the previous 3 months). * Not fluent in English (have used English in everyday speaking and reading for at least 10 years) * Unable or unwilling to give informed consent * Unwilling to abstain from alcohol and vigorous exercise for 24 hours, from food and drinks (other than water) for 3 hours and from non-prescription medications (other than oral contraception) for 2 days prior to testing.

Design outcomes

Primary

MeasureTime frameDescription
Cell-free Mitochondrial DNA5 minutes before task, and 5, 10, 20, 30, 45, 60, 75, 90 and 120 minutes after the task.Serum levels of mitochondrial DNA assessed from blood samples
Interleukin-65 minutes before to 5, 10, 20, 30, 45, 60, 75, 90, 120 post-task periodsPlasma levels of interleukin-6
Tumor Necrosis Factor-alpha5 minutes before to 5, 10, 20, 30, 45, 60, 75, 90, 120 post-task periodsPlasma levels of tumor necrosis factor-alpha

Secondary

MeasureTime frameDescription
Cortisol5 minutes before to 10, 20, 30, 45, 60 minutes post-task periodsCirculating levels of cortisol assessed by ELISA
Epinephrine5 minutes before to 5, 10, 20, 30, & 60 minutes post-task periodsLevels of epinephrine in plasma
Norepinephrine5 minutes before to 5, 10, 20, 30, & 60 minutes post-task periodsLevels of norepinephrine in plasma
Heart Rate VariabilityPre-task, task, and 1-5 and 6-10 minutes post taskInterbeat intervals of heart rate assessed by 3-lead EKG. Measures were taken continuously from 5 minutes before the task to 10 minutes after the task. Rsults were then averaged across 4 periods: 5 minutes prior to the task, the 5-minute task period, and 5-, and 10-minutes post task
Fatigue2 minutes before and 2, 60, and 120 minutes post-task periodsMomentary assessment of fatigue, measured as score on the fatigue subscale on the brief Profile of Mood States questionnaire. Scores range from 0 - 20, with higher scores reflecting more fatigue.
Heart Ratelast 5 minutes of baseline, 5-min task-period, first two 5 minutes post-task.Continuous measurement of heart rate was averaged across 4 periods: last 5 minutes of baseline, 5-min task-period, first two 5 minutes post-task.
Anxious Mood2 minutes before and 2-, 60- and 120-minutes post-task periodsMomentary assessment of anxious mood, measured as score on the anxiety subscale on the brief Profile of Mood States questionnaire in response to the task periods. Scores range from 0 - 16, with higher scores reflecting more anxious mood.
Vigor2 minutes before and 2-, 60-, and 120-minutes post-task periodsMomentary assessment of vigor, measured as score on the vigor subscale on the brief Profile of Mood States questionnaire in response to the task periods. Scores range from 0 - 12, with higher scores reflecting more vigor.
Depressed Mood2 minutes before and 2-, 60- and 120-minutes post-task periodsMomentary assessment of depressed mood, measured as score on the depression subscale on the brief Profile of Mood States questionnaire in response to the task periods. Scores range from 0 - 12, with higher scores reflecting more depressed mood.
Wellbeing2 minutes before and 2-, 60- and 120-minutes post-task periodsMomentary assessment of wellbeing, measured as score on the wellbeing subscale on the brief Profile of Mood States questionnaire in response to the task periods. Scores range from 0 - 12, with higher scores reflecting more wellbeing.
Calm Mood2 minutes before and 2-, 60-, and 120-minutes post-task periodsMomentary assessment of calm mood, measured as score on the calm subscale on the brief Profile of Mood States questionnaire in response to the task periods. Scores range from 0 - 16, with higher scores reflecting more calm mood.
Anger2 minutes before and 2-, 60-, and 120-minutes post-task periodsMomentary assessment of anger, measured as score on the anger subscale on the brief Profile of Mood States questionnaire in response to the task periods. Scores range from 0 - 12, with higher scores reflecting more anger.
Systolic Blood Pressure5 min pre-task and 5, 10, 20, 30, 45, 60, 75, 90, 120Blood pressure was assessed twice on 10 occasions across the protocol. The two readings on each occasion were averaged.
Diastolic Blood Pressure5 min pre-task and 5, 10, 20, 30, 45, 60, 75, 90, 120 post task onsetDiastolic blood pressure was assessed two times on 10 occasions across the protocol. On each occasion, the two measures were averaged.

Countries

United States

Participant flow

Recruitment details

Participants were recruited into this study between 7/23/2020 and 12/17/2021. Healthy volunteers were recruited from advertisements places around campus and through Pitt+Me, a registry of individuals interested in participating in research taking place at the University of Pittsburgh.

Pre-assignment details

Participants were scheduled for a screening telephone call to determine eligibility. Eligible participants were rescreened at 1st study visit and excluded if they did not meet eligibility criteria. We also excluded individuals on whom we could not insert a functioning intravenous catheter at the first study visit.

Participants by arm

ArmCount
Socio-evaluative Speech Stress, Then Control
Participants will attend two laboratory sessions. At the first session, participants will complete a socio-evaluative speech task, which is a widely used, highly effective way to investigate stress responses in a laboratory setting. Participants will prepare and deliver a brief, 3-minute speech defending themselves against an alleged transgression (e.g., running a stop sign). The speech will be delivered in front of a video camera, a mirror and an audience (the interviewer and another staff member). Participants will be told that their non-verbal behaviors are being evaluated. At the second session, participants will rest quietly for the same period as the speech task, in the absence of the stressor. Socio-evaluative speech task: 5-minute speech task designed to induce physiological arousal in a laboratory setting. Control, Quiet Rest: 5-minute quiet rest period.
36
Control, Then Socio-Evaluative Speech Stress
Participants will attend two laboratory sessions. At the first session, participants will rest quietly for 5 minutes. At the second session, participants will complete a socio-evaluative speech task, which is a widely used, highly effective way to investigate stress responses in a laboratory setting. Participants will prepare and deliver a brief, 3-minute speech defending themselves against an alleged transgression (e.g., running a stop sign). The speech will be delivered in front of a video camera, a mirror and an audience (the interviewer and another staff member). Participants will be told that their non-verbal behaviors are being evaluated. Socio-evaluative speech task: 5-minute speech task designed to induce physiological arousal in a laboratory setting. Control, Quiet Rest: 5-minute quiet rest period.
36
Total72

Withdrawals & dropouts

PeriodReasonFG000FG001
Session 2Lost to Follow-up31
Session 2Unable to insert IV - participant elected to withdraw88

Baseline characteristics

CharacteristicControl, Then Socio-Evaluative Speech StressTotalSocio-evaluative Speech Stress, Then Control
Age, Continuous31 Years
STANDARD_DEVIATION 8
31 Years
STANDARD_DEVIATION 9
32 Years
STANDARD_DEVIATION 9
Body Mass Index22.61 kg/M^2
STANDARD_DEVIATION 2.68
23.46 kg/M^2
STANDARD_DEVIATION 3.64
24.30 kg/M^2
STANDARD_DEVIATION 4.27
Diastolic Blood Pressure65.85 mmHg
STANDARD_DEVIATION 6.73
67.42 mmHg
STANDARD_DEVIATION 6.75
68.92 mmHg
STANDARD_DEVIATION 6.58
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Asian
4 Participants11 Participants7 Participants
Race (NIH/OMB)
Black or African American
3 Participants4 Participants1 Participants
Race (NIH/OMB)
More than one race
1 Participants4 Participants3 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
1 Participants1 Participants0 Participants
Race (NIH/OMB)
White
27 Participants52 Participants25 Participants
Region of Enrollment
United States
36 participants72 participants36 participants
Sex: Female, Male
Female
19 Participants34 Participants15 Participants
Sex: Female, Male
Male
17 Participants38 Participants21 Participants
Systolic Blood Pressure108.06 mmHg
STANDARD_DEVIATION 10.53
110.78 mmHg
STANDARD_DEVIATION 9.42
113.05 mmHg
STANDARD_DEVIATION 7.82

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
0 / 630 / 61
other
Total, other adverse events
0 / 630 / 61
serious
Total, serious adverse events
0 / 630 / 61

Outcome results

Primary

Cell-free Mitochondrial DNA

Serum levels of mitochondrial DNA assessed from blood samples

Time frame: 5 minutes before task, and 5, 10, 20, 30, 45, 60, 75, 90 and 120 minutes after the task.

ArmMeasureGroupValue (MEAN)Dispersion
Socio-evaluative Speech Stress SessionCell-free Mitochondrial DNA5 min pre-task165.79 Copies per uLStandard Deviation 143.01
Socio-evaluative Speech Stress SessionCell-free Mitochondrial DNA5 min175.45 Copies per uLStandard Deviation 144.03
Socio-evaluative Speech Stress SessionCell-free Mitochondrial DNA10 min414.74 Copies per uLStandard Deviation 1942.78
Socio-evaluative Speech Stress SessionCell-free Mitochondrial DNA20 min153.37 Copies per uLStandard Deviation 144.03
Socio-evaluative Speech Stress SessionCell-free Mitochondrial DNA30 min151.50 Copies per uLStandard Deviation 124.64
Socio-evaluative Speech Stress SessionCell-free Mitochondrial DNA45 min171.53 Copies per uLStandard Deviation 178.85
Socio-evaluative Speech Stress SessionCell-free Mitochondrial DNA60 min150.76 Copies per uLStandard Deviation 93.06
Socio-evaluative Speech Stress SessionCell-free Mitochondrial DNA75 min183.87 Copies per uLStandard Deviation 216.89
Socio-evaluative Speech Stress SessionCell-free Mitochondrial DNA90 min187.20 Copies per uLStandard Deviation 202.77
Socio-evaluative Speech Stress SessionCell-free Mitochondrial DNA120 min161.19 Copies per uLStandard Deviation 149.77
Control SessionCell-free Mitochondrial DNA75 min255.99 Copies per uLStandard Deviation 549.68
Control SessionCell-free Mitochondrial DNA5 min pre-task405.56 Copies per uLStandard Deviation 1218.33
Control SessionCell-free Mitochondrial DNA45 min172.03 Copies per uLStandard Deviation 155.38
Control SessionCell-free Mitochondrial DNA5 min164.45 Copies per uLStandard Deviation 133.03
Control SessionCell-free Mitochondrial DNA120 min232.64 Copies per uLStandard Deviation 279.89
Control SessionCell-free Mitochondrial DNA10 min296.62 Copies per uLStandard Deviation 629.78
Control SessionCell-free Mitochondrial DNA60 min215.58 Copies per uLStandard Deviation 437.87
Control SessionCell-free Mitochondrial DNA20 min213.27 Copies per uLStandard Deviation 511.28
Control SessionCell-free Mitochondrial DNA90 min223.99 Copies per uLStandard Deviation 272.97
Control SessionCell-free Mitochondrial DNA30 min163.41 Copies per uLStandard Deviation 147.62
Comparison: Results below present the condition (stress/control) by time interactions.p-value: 0.86Mixed Models Analysis
Primary

Interleukin-6

Plasma levels of interleukin-6

Time frame: 5 minutes before to 5, 10, 20, 30, 45, 60, 75, 90, 120 post-task periods

ArmMeasureGroupValue (MEAN)Dispersion
Socio-evaluative Speech Stress SessionInterleukin-630 min2.01 pg/mlStandard Deviation 1.44
Socio-evaluative Speech Stress SessionInterleukin-65 mins pre-task1.52 pg/mlStandard Deviation 1.29
Socio-evaluative Speech Stress SessionInterleukin-65 min1.76 pg/mlStandard Deviation 1.31
Socio-evaluative Speech Stress SessionInterleukin-610 min1.61 pg/mlStandard Deviation 1.24
Socio-evaluative Speech Stress SessionInterleukin-620 min2.05 pg/mlStandard Deviation 1.49
Socio-evaluative Speech Stress SessionInterleukin-645 min2.30 pg/mlStandard Deviation 1.7
Socio-evaluative Speech Stress SessionInterleukin-660 min2.50 pg/mlStandard Deviation 1.76
Socio-evaluative Speech Stress SessionInterleukin-675 min3.28 pg/mlStandard Deviation 3.61
Socio-evaluative Speech Stress SessionInterleukin-690 min3.80 pg/mlStandard Deviation 3.78
Socio-evaluative Speech Stress SessionInterleukin-6120 min4.50 pg/mlStandard Deviation 3.92
Control SessionInterleukin-675 min3.06 pg/mlStandard Deviation 2.84
Control SessionInterleukin-645 min2.15 pg/mlStandard Deviation 1.32
Control SessionInterleukin-65 mins pre-task1.40 pg/mlStandard Deviation 0.99
Control SessionInterleukin-6120 min4.72 pg/mlStandard Deviation 5.31
Control SessionInterleukin-65 min1.58 pg/mlStandard Deviation 0.94
Control SessionInterleukin-660 min2.27 pg/mlStandard Deviation 1.34
Control SessionInterleukin-610 min1.52 pg/mlStandard Deviation 0.94
Control SessionInterleukin-690 min2.91 pg/mlStandard Deviation 1.97
Control SessionInterleukin-620 min1.78 pg/mlStandard Deviation 1.01
Control SessionInterleukin-630 min1.85 pg/mlStandard Deviation 1.29
Comparison: Results present the condition (stress/control) by time interactions.p-value: 0.74Mixed Models Analysis
Primary

Tumor Necrosis Factor-alpha

Plasma levels of tumor necrosis factor-alpha

Time frame: 5 minutes before to 5, 10, 20, 30, 45, 60, 75, 90, 120 post-task periods

ArmMeasureGroupValue (MEAN)Dispersion
Socio-evaluative Speech Stress SessionTumor Necrosis Factor-alpha10 min6.59 pg/mlStandard Deviation 1.84
Socio-evaluative Speech Stress SessionTumor Necrosis Factor-alpha5 min6.62 pg/mlStandard Deviation 1.9
Socio-evaluative Speech Stress SessionTumor Necrosis Factor-alpha60 min6.41 pg/mlStandard Deviation 1.65
Socio-evaluative Speech Stress SessionTumor Necrosis Factor-alpha20 min6.70 pg/mlStandard Deviation 1.72
Socio-evaluative Speech Stress SessionTumor Necrosis Factor-alpha75 min6.58 pg/mlStandard Deviation 1.68
Socio-evaluative Speech Stress SessionTumor Necrosis Factor-alpha5 min pre-task5.92 pg/mlStandard Deviation 2.21
Socio-evaluative Speech Stress SessionTumor Necrosis Factor-alpha90 min3.78 pg/mlStandard Deviation 6.68
Socio-evaluative Speech Stress SessionTumor Necrosis Factor-alpha30 min6.45 pg/mlStandard Deviation 1.82
Socio-evaluative Speech Stress SessionTumor Necrosis Factor-alpha120 min3.92 pg/mlStandard Deviation 6.43
Socio-evaluative Speech Stress SessionTumor Necrosis Factor-alpha45 min6.61 pg/mlStandard Deviation 1.76
Control SessionTumor Necrosis Factor-alpha120 min6.66 pg/mlStandard Deviation 2.62
Control SessionTumor Necrosis Factor-alpha5 min pre-task6.10 pg/mlStandard Deviation 2.21
Control SessionTumor Necrosis Factor-alpha5 min6.81 pg/mlStandard Deviation 2.79
Control SessionTumor Necrosis Factor-alpha10 min6.28 pg/mlStandard Deviation 1.92
Control SessionTumor Necrosis Factor-alpha20 min6.79 pg/mlStandard Deviation 2.76
Control SessionTumor Necrosis Factor-alpha30 min6.35 pg/mlStandard Deviation 1.89
Control SessionTumor Necrosis Factor-alpha45 min6.74 pg/mlStandard Deviation 2.63
Control SessionTumor Necrosis Factor-alpha60 min6.52 pg/mlStandard Deviation 2.51
Control SessionTumor Necrosis Factor-alpha75 min6.79 pg/mlStandard Deviation 2.64
Control SessionTumor Necrosis Factor-alpha90 min6.75 pg/mlStandard Deviation 1.74
Comparison: Results below present the condition (stress/control) by time interactions.p-value: 0.52Mixed Models Analysis
Secondary

Anger

Momentary assessment of anger, measured as score on the anger subscale on the brief Profile of Mood States questionnaire in response to the task periods. Scores range from 0 - 12, with higher scores reflecting more anger.

Time frame: 2 minutes before and 2-, 60-, and 120-minutes post-task periods

ArmMeasureGroupValue (MEAN)Dispersion
Socio-evaluative Speech Stress SessionAngerPre-task0.30 score on a scaleStandard Deviation 1.03
Socio-evaluative Speech Stress SessionAnger2 min post-task0.70 score on a scaleStandard Deviation 1.57
Socio-evaluative Speech Stress SessionAnger60 min post task onset0.49 score on a scaleStandard Deviation 1.39
Socio-evaluative Speech Stress SessionAnger120 min post task onset0.45 score on a scaleStandard Deviation 1.51
Control SessionAnger120 min post task onset0.14 score on a scaleStandard Deviation 0.59
Control SessionAngerPre-task0.08 score on a scaleStandard Deviation 0.42
Control SessionAnger60 min post task onset0.16 score on a scaleStandard Deviation 0.72
Control SessionAnger2 min post-task0.20 score on a scaleStandard Deviation 1.05
Comparison: Results below present the condition (stress/control) by time interactions.p-value: 0.83Mixed Models Analysis
Secondary

Anxious Mood

Momentary assessment of anxious mood, measured as score on the anxiety subscale on the brief Profile of Mood States questionnaire in response to the task periods. Scores range from 0 - 16, with higher scores reflecting more anxious mood.

Time frame: 2 minutes before and 2-, 60- and 120-minutes post-task periods

ArmMeasureGroupValue (MEAN)Dispersion
Socio-evaluative Speech Stress SessionAnxious Mood2 min pre-task1.44 score on a scaleStandard Deviation 2.13
Socio-evaluative Speech Stress SessionAnxious Mood2 min post-task3.21 score on a scaleStandard Deviation 2.78
Socio-evaluative Speech Stress SessionAnxious Mood60 min post task onset1.56 score on a scaleStandard Deviation 2.21
Socio-evaluative Speech Stress SessionAnxious Mood120 min post task onset1.29 score on a scaleStandard Deviation 2.18
Control SessionAnxious Mood120 min post task onset1.02 score on a scaleStandard Deviation 2.46
Control SessionAnxious Mood2 min pre-task1.35 score on a scaleStandard Deviation 1.97
Control SessionAnxious Mood60 min post task onset1.24 score on a scaleStandard Deviation 2.3
Control SessionAnxious Mood2 min post-task0.93 score on a scaleStandard Deviation 1.97
Comparison: Results below present the condition (stress/control) by time interactions.p-value: 0.03Mixed Models Analysis
Secondary

Calm Mood

Momentary assessment of calm mood, measured as score on the calm subscale on the brief Profile of Mood States questionnaire in response to the task periods. Scores range from 0 - 16, with higher scores reflecting more calm mood.

Time frame: 2 minutes before and 2-, 60-, and 120-minutes post-task periods

ArmMeasureGroupValue (MEAN)Dispersion
Socio-evaluative Speech Stress SessionCalm Mood2 min pre-task9.09 score on a scaleStandard Deviation 2.85
Socio-evaluative Speech Stress SessionCalm Mood2 min post-task5.87 score on a scaleStandard Deviation 2.84
Socio-evaluative Speech Stress SessionCalm Mood60- min post task onset7.59 score on a scaleStandard Deviation 3.4
Socio-evaluative Speech Stress SessionCalm Mood120 min post task onset7.68 score on a scaleStandard Deviation 3.18
Control SessionCalm Mood120 min post task onset7.63 score on a scaleStandard Deviation 3.5
Control SessionCalm Mood2 min pre-task9.38 score on a scaleStandard Deviation 2.9
Control SessionCalm Mood60- min post task onset8.29 score on a scaleStandard Deviation 2.91
Control SessionCalm Mood2 min post-task8.83 score on a scaleStandard Deviation 3.39
Comparison: Results below present the condition (stress/control) by time interactions.p-value: 0.002Mixed Models Analysis
Secondary

Cortisol

Circulating levels of cortisol assessed by ELISA

Time frame: 5 minutes before to 10, 20, 30, 45, 60 minutes post-task periods

ArmMeasureGroupValue (MEAN)Dispersion
Socio-evaluative Speech Stress SessionCortisol5 min pre-task1.50 ug/dLStandard Deviation 0.72
Socio-evaluative Speech Stress SessionCortisol10 min post task onset1.46 ug/dLStandard Deviation 0.76
Socio-evaluative Speech Stress SessionCortisol20 min post task onset1.57 ug/dLStandard Deviation 0.86
Socio-evaluative Speech Stress SessionCortisol30 min post task onset1.49 ug/dLStandard Deviation 0.64
Socio-evaluative Speech Stress SessionCortisol45 min post task onset1.43 ug/dLStandard Deviation 0.62
Socio-evaluative Speech Stress SessionCortisol60 min post task onset1.35 ug/dLStandard Deviation 0.72
Control SessionCortisol45 min post task onset1.24 ug/dLStandard Deviation 0.66
Control SessionCortisol5 min pre-task1.48 ug/dLStandard Deviation 0.76
Control SessionCortisol30 min post task onset1.24 ug/dLStandard Deviation 0.64
Control SessionCortisol10 min post task onset1.30 ug/dLStandard Deviation 0.62
Control SessionCortisol60 min post task onset1.18 ug/dLStandard Deviation 0.6
Control SessionCortisol20 min post task onset1.30 ug/dLStandard Deviation 0.63
Comparison: Results below present the condition (stress/control) by time interactions.p-value: 0.005Mixed Models Analysis
Secondary

Depressed Mood

Momentary assessment of depressed mood, measured as score on the depression subscale on the brief Profile of Mood States questionnaire in response to the task periods. Scores range from 0 - 12, with higher scores reflecting more depressed mood.

Time frame: 2 minutes before and 2-, 60- and 120-minutes post-task periods

ArmMeasureGroupValue (MEAN)Dispersion
Socio-evaluative Speech Stress SessionDepressed Mood2 min pre-task0.32 score on a scaleStandard Deviation 0.91
Socio-evaluative Speech Stress SessionDepressed Mood2 min post-task0.46 score on a scaleStandard Deviation 1.2
Socio-evaluative Speech Stress SessionDepressed Mood60 min post task onset0.64 score on a scaleStandard Deviation 1.34
Socio-evaluative Speech Stress SessionDepressed Mood120 min post task onset0.41 score on a scaleStandard Deviation 1.12
Control SessionDepressed Mood120 min post task onset0.25 score on a scaleStandard Deviation 0.88
Control SessionDepressed Mood2 min pre-task0.23 score on a scaleStandard Deviation 0.79
Control SessionDepressed Mood60 min post task onset0.29 score on a scaleStandard Deviation 0.94
Control SessionDepressed Mood2 min post-task0.27 score on a scaleStandard Deviation 0.94
Comparison: Results below present the condition (stress/control) by time interactions.p-value: 0.51Mixed Models Analysis
Secondary

Diastolic Blood Pressure

Diastolic blood pressure was assessed two times on 10 occasions across the protocol. On each occasion, the two measures were averaged.

Time frame: 5 min pre-task and 5, 10, 20, 30, 45, 60, 75, 90, 120 post task onset

ArmMeasureGroupValue (MEAN)Dispersion
Socio-evaluative Speech Stress SessionDiastolic Blood Pressure10 min post task onset72.65 mmHgStandard Deviation 12.58
Socio-evaluative Speech Stress SessionDiastolic Blood Pressure45 min post task onset79.03 mmHgStandard Deviation 14.32
Socio-evaluative Speech Stress SessionDiastolic Blood Pressure5 min post-task onset72.00 mmHgStandard Deviation 11.71
Socio-evaluative Speech Stress SessionDiastolic Blood Pressure60 min post task onset71.80 mmHgStandard Deviation 13.54
Socio-evaluative Speech Stress SessionDiastolic Blood Pressure20 min post task onset79.58 mmHgStandard Deviation 18.09
Socio-evaluative Speech Stress SessionDiastolic Blood Pressure75 min post task onset68.02 mmHgStandard Deviation 12.45
Socio-evaluative Speech Stress SessionDiastolic Blood Pressure5 min pre-task67.69 mmHgStandard Deviation 9.47
Socio-evaluative Speech Stress SessionDiastolic Blood Pressure90 min post task onset66.37 mmHgStandard Deviation 10.58
Socio-evaluative Speech Stress SessionDiastolic Blood Pressure120 min post task onset66.30 mmHgStandard Deviation 12.59
Socio-evaluative Speech Stress SessionDiastolic Blood Pressure30 min post task onset81.57 mmHgStandard Deviation 16.62
Control SessionDiastolic Blood Pressure120 min post task onset64.10 mmHgStandard Deviation 12.25
Control SessionDiastolic Blood Pressure5 min pre-task65.74 mmHgStandard Deviation 10.18
Control SessionDiastolic Blood Pressure5 min post-task onset66.02 mmHgStandard Deviation 9.46
Control SessionDiastolic Blood Pressure10 min post task onset65.17 mmHgStandard Deviation 9.95
Control SessionDiastolic Blood Pressure20 min post task onset65.27 mmHgStandard Deviation 10.43
Control SessionDiastolic Blood Pressure30 min post task onset66.42 mmHgStandard Deviation 10.15
Control SessionDiastolic Blood Pressure45 min post task onset65.71 mmHgStandard Deviation 10.12
Control SessionDiastolic Blood Pressure60 min post task onset66.17 mmHgStandard Deviation 10.59
Control SessionDiastolic Blood Pressure75 min post task onset65.86 mmHgStandard Deviation 12.07
Control SessionDiastolic Blood Pressure90 min post task onset64.34 mmHgStandard Deviation 10.12
Comparison: Results-interaction between time\^2 and conditionp-value: <0.001Mixed Models Analysis
Secondary

Epinephrine

Levels of epinephrine in plasma

Time frame: 5 minutes before to 5, 10, 20, 30, & 60 minutes post-task periods

ArmMeasureGroupValue (MEAN)Dispersion
Socio-evaluative Speech Stress SessionEpinephrine5 min pre-task50.56 pg/mlStandard Deviation 20.09
Socio-evaluative Speech Stress SessionEpinephrine5 min post task onset54.01 pg/mlStandard Deviation 23.87
Socio-evaluative Speech Stress SessionEpinephrine10 min post task onset49.81 pg/mlStandard Deviation 18.69
Socio-evaluative Speech Stress SessionEpinephrine20 min post task onset47.95 pg/mlStandard Deviation 18.12
Socio-evaluative Speech Stress SessionEpinephrine30 min post task onset47.08 pg/mlStandard Deviation 16.63
Socio-evaluative Speech Stress SessionEpinephrine60 min post task onset48.34 pg/mlStandard Deviation 17.78
Control SessionEpinephrine30 min post task onset44.26 pg/mlStandard Deviation 18.35
Control SessionEpinephrine5 min pre-task48.62 pg/mlStandard Deviation 21.67
Control SessionEpinephrine20 min post task onset45.16 pg/mlStandard Deviation 17.38
Control SessionEpinephrine5 min post task onset47.46 pg/mlStandard Deviation 21.19
Control SessionEpinephrine60 min post task onset41.64 pg/mlStandard Deviation 16.43
Control SessionEpinephrine10 min post task onset52.48 pg/mlStandard Deviation 28.98
Comparison: Results below present the condition (stress/control) by time interactions.p-value: 0.92Mixed Models Analysis
Secondary

Fatigue

Momentary assessment of fatigue, measured as score on the fatigue subscale on the brief Profile of Mood States questionnaire. Scores range from 0 - 20, with higher scores reflecting more fatigue.

Time frame: 2 minutes before and 2, 60, and 120 minutes post-task periods

ArmMeasureGroupValue (MEAN)Dispersion
Socio-evaluative Speech Stress SessionFatiguePre-task4.76 score on scaleStandard Deviation 4.02
Socio-evaluative Speech Stress SessionFatiguepost-task2.59 score on scaleStandard Deviation 2.75
Socio-evaluative Speech Stress SessionFatigue60 min post task onset5.79 score on scaleStandard Deviation 4.15
Socio-evaluative Speech Stress SessionFatigue120 min post task onset5.50 score on scaleStandard Deviation 4.5
Control SessionFatigue120 min post task onset5.41 score on scaleStandard Deviation 4.36
Control SessionFatiguePre-task5.47 score on scaleStandard Deviation 3.72
Control SessionFatigue60 min post task onset6.48 score on scaleStandard Deviation 4.62
Control SessionFatiguepost-task5.36 score on scaleStandard Deviation 3.86
Comparison: Results \_condition (stress/control) by time interactions.p-value: 0.008Mixed Models Analysis
Secondary

Heart Rate

Continuous measurement of heart rate was averaged across 4 periods: last 5 minutes of baseline, 5-min task-period, first two 5 minutes post-task.

Time frame: last 5 minutes of baseline, 5-min task-period, first two 5 minutes post-task.

ArmMeasureGroupValue (MEAN)Dispersion
Socio-evaluative Speech Stress SessionHeart RateMean of 5 min pre-task65.60 Beats per minuteStandard Deviation 9.57
Socio-evaluative Speech Stress SessionHeart Ratemean of 5 min task period79.27 Beats per minuteStandard Deviation 14.44
Socio-evaluative Speech Stress SessionHeart Ratemean of min 1-5 post-task71.37 Beats per minuteStandard Deviation 10.83
Socio-evaluative Speech Stress SessionHeart Ratemean of min 6-10 post-task66.00 Beats per minuteStandard Deviation 9.46
Control SessionHeart Ratemean of min 6-10 post-task65.03 Beats per minuteStandard Deviation 9.24
Control SessionHeart RateMean of 5 min pre-task66.76 Beats per minuteStandard Deviation 9.53
Control SessionHeart Ratemean of min 1-5 post-task67.43 Beats per minuteStandard Deviation 9.2
Control SessionHeart Ratemean of 5 min task period66.36 Beats per minuteStandard Deviation 9.46
p-value: <0.001Mixed Models Analysis
Secondary

Heart Rate Variability

Interbeat intervals of heart rate assessed by 3-lead EKG. Measures were taken continuously from 5 minutes before the task to 10 minutes after the task. Rsults were then averaged across 4 periods: 5 minutes prior to the task, the 5-minute task period, and 5-, and 10-minutes post task

Time frame: Pre-task, task, and 1-5 and 6-10 minutes post task

ArmMeasureGroupValue (MEAN)Dispersion
Socio-evaluative Speech Stress SessionHeart Rate VariabilityMean across 5 min pre-task6.50 log normal millisecondsStandard Deviation 1.05
Socio-evaluative Speech Stress SessionHeart Rate VariabilityMean across 5 min task period5.94 log normal millisecondsStandard Deviation 0.96
Socio-evaluative Speech Stress SessionHeart Rate VariabilityMean across minutes 1-5 post-task6.18 log normal millisecondsStandard Deviation 0.97
Socio-evaluative Speech Stress SessionHeart Rate VariabilityMean across 6-10 minutes post-task6.30 log normal millisecondsStandard Deviation 0.93
Control SessionHeart Rate VariabilityMean across 6-10 minutes post-task6.43 log normal millisecondsStandard Deviation 0.91
Control SessionHeart Rate VariabilityMean across 5 min pre-task6.58 log normal millisecondsStandard Deviation 0.81
Control SessionHeart Rate VariabilityMean across minutes 1-5 post-task6.37 log normal millisecondsStandard Deviation 0.85
Control SessionHeart Rate VariabilityMean across 5 min task period6.50 log normal millisecondsStandard Deviation 0.92
Comparison: Results-interaction between time\^2 and conditionp-value: 0.002Mixed Models Analysis
Secondary

Norepinephrine

Levels of norepinephrine in plasma

Time frame: 5 minutes before to 5, 10, 20, 30, & 60 minutes post-task periods

ArmMeasureGroupValue (MEAN)Dispersion
Socio-evaluative Speech Stress SessionNorepinephrine5 min pre-task522.86 pg/mlStandard Deviation 228.82
Socio-evaluative Speech Stress SessionNorepinephrine5 min post-task onset540.39 pg/mlStandard Deviation 178.62
Socio-evaluative Speech Stress SessionNorepinephrine10 min post-task526.93 pg/mlStandard Deviation 187.47
Socio-evaluative Speech Stress SessionNorepinephrine20 min post-task494.17 pg/mlStandard Deviation 173.34
Socio-evaluative Speech Stress SessionNorepinephrine30 min post-task477.84 pg/mlStandard Deviation 191.16
Socio-evaluative Speech Stress SessionNorepinephrine60 min post-task472.74 pg/mlStandard Deviation 156.83
Control SessionNorepinephrine30 min post-task476.14 pg/mlStandard Deviation 155.51
Control SessionNorepinephrine5 min pre-task480.48 pg/mlStandard Deviation 175.92
Control SessionNorepinephrine20 min post-task470.70 pg/mlStandard Deviation 172.5
Control SessionNorepinephrine5 min post-task onset485.44 pg/mlStandard Deviation 157.6
Control SessionNorepinephrine60 min post-task461.97 pg/mlStandard Deviation 160.05
Control SessionNorepinephrine10 min post-task484.38 pg/mlStandard Deviation 151.81
Comparison: Results below present the condition (stress/control) by time interactions.p-value: 0.04Mixed Models Analysis
Secondary

Systolic Blood Pressure

Blood pressure was assessed twice on 10 occasions across the protocol. The two readings on each occasion were averaged.

Time frame: 5 min pre-task and 5, 10, 20, 30, 45, 60, 75, 90, 120

ArmMeasureGroupValue (MEAN)Dispersion
Socio-evaluative Speech Stress SessionSystolic Blood Pressure5 min pre-task111.18 mmHgStandard Error 9.47
Socio-evaluative Speech Stress SessionSystolic Blood Pressure5 min post-task120.29 mmHgStandard Error 11.71
Socio-evaluative Speech Stress SessionSystolic Blood Pressure10 min post-task120.02 mmHgStandard Error 12.58
Socio-evaluative Speech Stress SessionSystolic Blood Pressure20 min post-task131.55 mmHgStandard Error 18.09
Socio-evaluative Speech Stress SessionSystolic Blood Pressure30 min post-task135.63 mmHgStandard Error 16.62
Socio-evaluative Speech Stress SessionSystolic Blood Pressure45 min post-task133.42 mmHgStandard Error 14.32
Socio-evaluative Speech Stress SessionSystolic Blood Pressure60 min post-task125.43 mmHgStandard Error 13.54
Socio-evaluative Speech Stress SessionSystolic Blood Pressure75 min post-task120.61 mmHgStandard Error 12.45
Socio-evaluative Speech Stress SessionSystolic Blood Pressure90 min post-task117.15 mmHgStandard Error 10.58
Socio-evaluative Speech Stress SessionSystolic Blood Pressure120 min post-tsk115.45 mmHgStandard Error 12.59
Control SessionSystolic Blood Pressure75 min post-task109.59 mmHgStandard Error 12.07
Control SessionSystolic Blood Pressure5 min pre-task109.43 mmHgStandard Error 10.18
Control SessionSystolic Blood Pressure45 min post-task109.14 mmHgStandard Error 10.12
Control SessionSystolic Blood Pressure5 min post-task110.70 mmHgStandard Error 9.46
Control SessionSystolic Blood Pressure120 min post-tsk108.32 mmHgStandard Error 12.25
Control SessionSystolic Blood Pressure10 min post-task109.38 mmHgStandard Error 9.95
Control SessionSystolic Blood Pressure60 min post-task109.46 mmHgStandard Error 10.59
Control SessionSystolic Blood Pressure20 min post-task109.23 mmHgStandard Error 10.43
Control SessionSystolic Blood Pressure90 min post-task109.29 mmHgStandard Error 10.12
Control SessionSystolic Blood Pressure30 min post-task108.98 mmHgStandard Error 10.15
Comparison: Results-interaction between time2 and conditionp-value: <0.001Mixed Models Analysis
Secondary

Vigor

Momentary assessment of vigor, measured as score on the vigor subscale on the brief Profile of Mood States questionnaire in response to the task periods. Scores range from 0 - 12, with higher scores reflecting more vigor.

Time frame: 2 minutes before and 2-, 60-, and 120-minutes post-task periods

ArmMeasureGroupValue (MEAN)Dispersion
Socio-evaluative Speech Stress SessionVigor60 min post task onset1.39 score on a scaleStandard Deviation 1.89
Socio-evaluative Speech Stress SessionVigor2 min pre-task1.84 score on a scaleStandard Deviation 1.97
Socio-evaluative Speech Stress SessionVigor120 min post task onset1.91 score on a scaleStandard Deviation 2.3
Socio-evaluative Speech Stress SessionVigor2 min post-task3.19 score on a scaleStandard Deviation 2.28
Control SessionVigor120 min post task onset1.66 score on a scaleStandard Deviation 2.09
Control SessionVigor2 min pre-task1.65 score on a scaleStandard Deviation 1.87
Control SessionVigor60 min post task onset1.03 score on a scaleStandard Deviation 1.53
Control SessionVigor2 min post-task1.54 score on a scaleStandard Deviation 1.81
Comparison: Results below present the condition (stress/control) by time interactions.p-value: 0.04Mixed Models Analysis
Secondary

Wellbeing

Momentary assessment of wellbeing, measured as score on the wellbeing subscale on the brief Profile of Mood States questionnaire in response to the task periods. Scores range from 0 - 12, with higher scores reflecting more wellbeing.

Time frame: 2 minutes before and 2-, 60- and 120-minutes post-task periods

ArmMeasureGroupValue (MEAN)Dispersion
Socio-evaluative Speech Stress SessionWellbeing2 min pre-task4.25 score on a scaleStandard Deviation 2.11
Socio-evaluative Speech Stress SessionWellbeing2 min post-task3.56 score on a scaleStandard Deviation 2.19
Socio-evaluative Speech Stress SessionWellbeing60-min post-task3.61 score on a scaleStandard Deviation 2.36
Socio-evaluative Speech Stress SessionWellbeing120-min post-task3.93 score on a scaleStandard Deviation 2.7
Control SessionWellbeing120-min post-task3.82 score on a scaleStandard Deviation 2.52
Control SessionWellbeing2 min pre-task4.10 score on a scaleStandard Deviation 2.04
Control SessionWellbeing60-min post-task3.81 score on a scaleStandard Deviation 2.31
Control SessionWellbeing2 min post-task3.93 score on a scaleStandard Deviation 2.34
Comparison: Results below present the condition (stress/control) by time interactions.p-value: 0.49Mixed Models Analysis

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026