Biological Response to Brief Psychological Challenge
Condition: Acute Inflammatory Response to Psychological Stress
MeSH terms: Stress, Psychological
Study type: Interventional

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.
    

Intervention name(s): Socio-evaluative speech task; Control, Quiet Rest
Intervention type(s): Behavioral; Behavioral
Intervention description(s): 5-minute speech task designed to induce physiological arousal in a laboratory setting.; 5-minute quiet rest period.
Allocation: Randomized
Intervention model: Crossover Assignment
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.
Masking: Single (Outcomes Assessor)
Primary purpose: Basic Science