Anticipatory stress: a model to study cardiovascular and sympathetic responses to mental stress?

Cardiovascular reactivity to acute laboratory mental stress is predictive of future adverse health outcomes. Specifically, greater increases in blood pressure in response to mental stress are associated with increased cardiovascular disease risk (Chida & Steptoe, 2010). However, the underlying mechanisms responsible for altered blood pressure reactivity to mental stress have not been elucidated. While the sympathetic nervous system plays an integral role in the canonical response to acute stress exposure, interindividual responses in direct measures of efferent sympathetic outflow (i.e. muscle sympathetic nerve activity; MSNA) during mental stress are highly variable. Indeed, previous studies have observed increased, decreased or unchanged MSNA in response to mental stress. Although the reason(s) for this interindividual variability remain unclear, laboratory-based mental stress tasks are often limited by irregular breathing, talking, movement and administrator feedback, many of which also affect efferent sympathetic outflow. The Trier social stress test (TSST) is commonly utilized in psychology to study the acute stress response to tasks that are thought to more closely mirror stressors encountered in daily life (e.g., anticipation and social evaluation) (Allen et al. 2014). The TSST consists of an anticipatory phase, speech phase and mental math phase. Critically, the anticipatory phase is largely devoid of confounding variables present in traditional mental stress tasks (e.g., Stroop color word task). In a recent publication in The Journal of Physiology, Bigalke et al. (2022) measured beat-to-beat blood pressure via finger photoplethysmography and MSNA via peroneal microneurography during the TSST in 26 healthy participants (11 males, 15 females; 25 ± 6 years). This built upon previous studies that intermittently measured blood pressure and plasma noradrenaline to determine the cardiovascular and sympathetic responses to the TSST. In the present investigation, Bigalke et al. (2022) observed consistent reductions in MSNA burst frequency during the anticipatory phase and more variable MSNA responses during the speech and mental math phases. This decrease in MSNA was negatively correlated with increases in diastolic blood pressure only during the anticipatory phase, with a trend towards significance (P = 0.051) when assessed during the mental math phase. Active baroreflex resetting and blood pressure fluctuations occur during the onset (e.g., first 2 min) of mental stress. Therefore, the lack of association between MSNA and diastolic blood pressure during the speech and mental math phases may be due to inclusion of the first 2min of each stressor in data analysis. Another possible explanation (as outlined by the authors) may be the influence of speaking on the sympathetic response during these phases. Bigalke et al. (2022) also demonstrated that changes in MSNA burst frequency during the anticipatory phase were positively associated with changes in burst frequency during both the speech and the mental math phases. Our interpretation of the authors’ discussion is that future studies may be able to administer the 5-min anticipatory phase without the ensuing 10 min of acute mental stress typical of the TSST, making the protocol less time intensive for both researchers and participants. However, while the authors concluded that changes in MSNA during the anticipatory phase predicted MSNA responses during mental stress, they did not provide cutoff values for responders and non-responders to mental stress, limiting the utility of this relation. While this represents an important first step, future studies are necessary to extend these findings and develop a predictive model. Interestingly, participants included in this study appear to have moderately severe symptoms of anxiety, with mean Spielberger trait anxiety inventory scores almost reaching the threshold of clinical anxiety (e.g., cutoff score of 40) and mean Beck anxiety inventory scores falling close to or within the mild to moderate anxiety range (e.g., score of 10–18 indicates mild to moderate anxiety). These scores may indicate that these participants are more vulnerable to anticipatory stress due to trait anxiety characteristics (Julian, 2011). Whether a study population harboring trait anxiety and somatic symptoms of anxiety alters cardiovascular and sympathetic responses to the TSST is unclear. Further, whether these measures of anxiety also influence the relation in physiological responses between the anticipatory phase and speech and mental math phases is unknown. It is important that future studies consider the impact of anxiety symptomatology on cardiovascular and sympathetic responsiveness during the TSST. In addition, it is worth noting that differences in MSNA burst amplitude have been previously observed between adults with and without generalized anxiety disorder during the anticipatory phase prior to mental stress (Holwerda et al. 2018). Similar to Bigalke et al. (2022), future studies would benefit from quantifying MSNA beyond burst frequency and incidence. Finally, it will be important to examine how these responses to the TSST may differ in adults with diagnosed psychological illnesses (e.g., depression) and stress-related disorders (e.g., post-traumatic stress disorder) to better understand potential alterations in the stress response and how they may contribute to elevated cardiovascular disease risk. It is important to note that at present, blood pressure responses to mental stress are linked to future cardiovascular disease risk; whether MSNA responses to mental stress are also indicative of heightened future cardiovascular disease risk remains to be elucidated (Chida & Steptoe, 2010). While it is important to assess mechanisms contributing to blood pressure regulation during stress (e.g., efferent sympathetic outflow), evidence suggests that MSNA does not dictate the blood pressure response during mental