Biological Response to Brief Psychological Challenge

Not Applicable

Completed

Conditions: Acute Inflammatory Response to Psychological Stress

Interventions: Behavioral: Socio-evaluative speech task
Behavioral: Control, Quiet Rest

Registration Number: NCT04078035

Lead Sponsor: University of Pittsburgh

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 72

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Socio-evaluative Speech Stress, then Control	Control, Quiet Rest	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 Stress, then Control	Socio-evaluative speech task	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.
Control, then Socio-Evaluative Speech Stress	Control, Quiet Rest	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.
Control, then Socio-Evaluative Speech Stress	Socio-evaluative speech task	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.

Primary Outcome Measures

Name	Time	Method
Cell-free Mitochondrial DNA	5 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-6	5 minutes before to 5, 10, 20, 30, 45, 60, 75, 90, 120 post-task periods	Plasma levels of interleukin-6
Tumor Necrosis Factor-alpha	5 minutes before to 5, 10, 20, 30, 45, 60, 75, 90, 120 post-task periods	Plasma levels of tumor necrosis factor-alpha

Secondary Outcome Measures

Name	Time	Method
Cortisol	5 minutes before to 10, 20, 30, 45, 60 minutes post-task periods	Circulating levels of cortisol assessed by ELISA
Norepinephrine	5 minutes before to 5, 10, 20, 30, & 60 minutes post-task periods	Levels of norepinephrine in plasma
Depressed Mood	2 minutes before and 2-, 60- and 120-minutes post-task periods	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.
Fatigue	2 minutes before and 2, 60, and 120 minutes post-task periods	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.
Calm Mood	2 minutes before and 2-, 60-, and 120-minutes post-task periods	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.
Heart Rate Variability	Pre-task, task, and 1-5 and 6-10 minutes post task	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
Systolic Blood Pressure	5 min pre-task and 5, 10, 20, 30, 45, 60, 75, 90, 120	Blood pressure was assessed twice on 10 occasions across the protocol. The two readings on each occasion were averaged.
Diastolic Blood Pressure	5 min pre-task and 5, 10, 20, 30, 45, 60, 75, 90, 120 post task onset	Diastolic blood pressure was assessed two times on 10 occasions across the protocol. On each occasion, the two measures were averaged.
Epinephrine	5 minutes before to 5, 10, 20, 30, & 60 minutes post-task periods	Levels of epinephrine in plasma
Anger	2 minutes before and 2-, 60-, and 120-minutes post-task periods	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.
Wellbeing	2 minutes before and 2-, 60- and 120-minutes post-task periods	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.
Heart Rate	last 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 Mood	2 minutes before and 2-, 60- and 120-minutes post-task periods	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.
Vigor	2 minutes before and 2-, 60-, and 120-minutes post-task periods	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.