CO₂ challenge-evoked hormonal changes predicting TSST changes in cortisol and subjective distress

The importance of stressor response in relation to the development of psychopathology has been recognized for decades, yet the relationship is not fully understood. The Trier Social Stress Test (TSST) is an established conditioned stressor and frequently used to assess cortisol response to acute stress in different psychopathologies. The 35 % CO₂ Challenge is a biological stressor and has mostly been utilized to assess subjective responses in anxiety related disorders. In the current study (N=189), we assessed the hormonal effects (cortisol, testosterone) and subjective distress (stress, anxiety, and fear) of the 35 % CO₂ Challenge, and several days later, assessed the hormonal and subjective distress effects of the TSST in a mixed-sex, college-aged sample, to test for predictive effects of the 35 % CO₂ Challenge on TSST-evoked outcomes. No testosterone by cortisol interaction effects were found in females. In males, the 35 % CO₂ Challenge-evoked interaction of testosterone and cortisol predicted TSST-evoked subjective stress, anxiety, and fear, with higher concentrations of testosterone predicting subjective distress, but only at (relatively) low concentrations of cortisol (one standard deviation below mean concentrations). This result - in line with the dual-hormone hypothesis - suggests the 35 % CO₂ Challenge could be utilized in a wider array of laboratory stress response research.