Biological Response to Brief Psychological Challenge

University of Pittsburgh72 enrolled

Overview

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.

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.

Eligibility

Sex: ALLMin age: 20 YearsMax age: 50 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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.

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

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

Secondary Outcomes

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.

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

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

Cortisol

Circulating levels of cortisol assessed by ELISA

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

Epinephrine

Levels of epinephrine in plasma

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

Norepinephrine

Levels of norepinephrine in plasma

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

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

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

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

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

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

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

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

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

Biological Response to Brief Psychological Challenge

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes