Dr. Damian Sendler COVID-19 Stress Study Results Are In

Damian Sendler: Stress researchers in psychology and neuroscience face new challenges in the wake of the COVID-19 pandemic. The Trier Social Stress Test, a widely used experimental paradigm, uses physical social encounters to elicit stress through social-evaluative threat. Traditional stress induction methods are difficult to implement because of current lockdowns and contact restrictions. As the pandemic is expected to increase the prevalence of stress-related mental disorders, stress research is critical. Virtual reality (VR), pre-recordings (PR), and online adaptations (OAR) are some recent trends in stress induction research that are being examined. As well as being critical for COVID-19 stress research, these methods are sure to spark interest in stress research for years to come. It is possible that they can be used in new settings and with participants who are either homebound or movement-restricted. New experimental variations are possible, which could improve procedures and even the way stress is conceptualized. With all due respect to stress researchers, the COVID-19 pandemic could eventually serve as a driving force for progress.

Damian Jacob Sendler: We all know what it’s like to be stressed out, because in our daily lives, we run into a slew of stressful situations (e.g., having to give an oral presentation at work, acting under time pressure, or facing the next exam). The neuroendocrine stress response is triggered when the organism’s internal resources are taxed due to an imbalance between external and internal demands, which is commonly how stress is defined (Lazarus, 1993). Adrenal medulla releases catecholamines like adrenaline and noradrenaline as a result of this activation of the sympathetic nervous system (SNS), which causes heart rate, blood pressure or sweating to rise (Goldstein, 1987; Jols and Baraman 2009). It also activates the hypothalamus-pituitary-adrenal-cortical (HPA) system (Aguilera, 2011). Glucocorticoids, such as cortisol, are then released into the bloodstream, where they affect cells all over the body (de Kloet et al., 2005). Neurocognitive processes like decision-making, memory, and extinction learning and relapse have all been shown to be affected by the effects of the glucocorticoid hormone (Meir Drexler et al., 2019). The organism’s current environment is assumed to have induced the changes. Consequently, the acute stress response is seen as an adaptive means of coping. However, the body can be harmed if stressed out on a regular basis or in excess (Epel et al., 2018; McEwen, 1998). The precise mechanisms and complex interactions between genetic and environmental risk factors over the course of a person’s lifetime remain poorly understood, despite the significant progress made in recent decades (Ehlert et al., 2001; Zänkert et al., 2019).

Dr. Sendler: Globally, the COVID-19 pandemic is a universal and chronic stressor that affects everyone, regardless of their socioeconomic status. As a result, an unprecedented public mental health crisis could result (Pfefferbaum and North, 2020). With mental illness on the rise (Baxter et al., 2014; Cohen and Janicki-Deverts, 2012; DeVries and Wilkerson, 2003), this review article (1) highlights the urgent need for experimental stress research using standardized stresses during the current COVID-19 pandemic; (2) explores the conceptual and methodological challenges the discipline faces in this unusual situation; and (3) concludes with some recommendations for future research.

More and more people are suffering from anxiety and depression as a result of stress-related mental disorders in recent years (Baxter et al. 2014; Cohen and Janicki-Deverts, 2012; DeVries and Wilkerson, 2003), which is leading to personal hardships as well as monetary and social issues for society at large (Baxter et al., 2014). (Hassard et al., 2018; Trautmann et al., 2016). Many mental health disorders, including posttraumatic stress disorder (PTSD; Yehuda, 2002), anxiety disorders (Sandn and Chorot, 1993; Shin and Liberzon, 2010), and depression (Colodro-Conde et al., 2018; Musliner et al., 2015), have been linked to stress in etiological diathesis-stress models (Cohen et al., 2016; Cohen et al., 2007; Ottenweller (Thompson et al., 2007).

To understand these mental disorders, it is important to note that the COVID-19 pandemic may serve as an additional source of stress. These three aspects of stressors (novelty, unpredictability, and uncontrollability) support this hypothesis (Mason, 1968). In addition, the political measures imposed to stop the virus from spreading may also be viewed as stressful by those who have been infected. Surveys of the general public have confirmed the latter (Groarke et al., 2020; Kowal et al., 2020; Qiu et al., 2020). Many people are concerned about the spread of COVID-19, their daily routines being disrupted, and the general lack of certainty about the future (Amirkhan, 2021; Hagger et al., 2020; Mahmud et al., 2021). In addition, health care workers (Bohlken et al., 2020; Chew et al., 2020; Spoorthy et al., 2020) and those who have lost their jobs or are experiencing financial difficulties as a result of the pandemic report increased stress levels (Achdut and Refaeli, 2020; Blustein et al., 2020). Similar stress was found in those who felt isolated due to a lack of social interaction (Brooks et al., 2020; Groarke et al., 2020), as well as parents who had difficulty caring for their children because of the closure of local schools and kindergartens (Brown et al., 2020). As a result, the COVID-19 pandemic must be considered a unique stressor that will have serious consequences for health and well-being because it is both chronic and universal.

There’s been an increase in anxiety and depression during the current pandemic, with specific factors such as social or economic disadvantages influencing stress perceptions, recent studies have found (Bueno-Notivol et al., 2021; Ettman et al., 2020; Kowal et al., 2020). Probability-based methods were used in a nationally representative sample by Holman et al. (2020) to predict the progression of mental disorders at an early but critical stage of the pandemic. There is a higher risk of mental health problems among people with pre-existing health conditions, those who have been exposed to secondary stressors, and those who have been exposed to COVID-19-related media coverage. According to Boyraz and Legros (2020) and Bridgland et al. (2021), the pandemic may even be a traumatic experience that could lead to an increase in the prevalence of posttraumatic stress disorder (PTSD).

Mental health problems have spiked in the past in the wake of tragedies like 9/11 (Laugharne and colleagues in 2007, Lowell and colleagues in 2018, Neria and colleagues in 2011, Yehuda in 2002), school shootings (Rossin-Slater and colleagues in 2020), and earthquakes and hurricanes (Ironson and colleagues in 1997), among others. Great Recession 2007–2009 exacerbated mental health problems (Margerison-Zilko et al., 2016). It has been shown that mental health problems have increased during pandemics, such as the Middle East Respiratory Syndrome (MERS; for example Jeong et al., 2016) and the Severe Acute Respiratory Syndrome (SARS; for example Chan et al., 2006). With these findings, one can conclude that the COVID-19 pandemic as a global and long-lasting stressor will have comparable devastating consequences. According to Kickbusch et al. (2020), this is the greatest threat to health and well-being, social welfare, and the global economy in living memory, implying greater destructive power than every previous crisis of the recent past. Fig. 1 provides a schematic diagram of stressors encountered in laboratory contexts and in everyday life, along with their relevance for basic, clinical, and epidemiological stress research, to illustrate the implications of the COVID-19 pandemic on society and research.

Here is a visual representation of how stress can be induced in the lab or in the real world, as well as how this information can be used in basic, clinical, and epidemiological stress studies. Acute and well-controlled stress induction paradigms are used in the laboratory, but they are artificial. We face a variety of long-term stressors in our daily lives that are of interest to basic, clinical, and epidemiological stress studies. Because of their high ecological validity, field stressors are well-recognized in basic stress research. As a result, stress research has already focused on certain types of stressful or traumatic events. For clinical, epidemiological, and basic stress research, the COVID-19 pandemic can be regarded as a chronic field stressor. BioRender.com was used to generate this image.

Yet another approach claims that stress, or more specifically, overexertion, is to blame for the still-unsolved variation in the actual distribution of COVID-19. Amirkhan (2021), for example, hypothesized that stress would increase the individual susceptibility to COVID-19 infection given the unequal distribution of infections across countries and social classes. A growing body of research shows that chronic stress has a negative impact on the body’s immune system, resulting in an increased risk of infection or illness as well as a longer duration (Glaser and Kiecolt-Glaser, 2005).

We can conclude that stress is linked to poor health outcomes under COVID-19 conditions, highlighting the importance of making the pandemic an urgent public health priority (Ettman et al., 2020; Pfefferbaum and North, 2020). In light of this, stress research has a particularly high societal impact. To fully comprehend the COVID-19 pandemic’s consequences, epidemiological and clinical perspectives are required (Daly and Robinson, 2021; Ettman et al., 2020; Khan et al., 2020). Basic stress research, on the other hand, is particularly relevant at this time of pandemic, as will be described below.

Basic stress research, in addition to epidemiological and clinical stress research, can provide fundamental insights that are essential for clinical applications, we argue. Earlier studies on acute laboratory stress have already had a direct or indirect impact on clinical practice in this context. The first evidence that a lack of habituation to repeated stress exposure in cortisol response kinetics might be a marker for health was provided by Pruessner et al. (1997) and Kirschbaum et al. (1995). Cortisol responsiveness in atopic diseases was found to be diminished in the studies conducted by the Buske-Kirschbaum team in 2003 and 2010. Finally, these results can be incorporated into McEwen’s theoretical considerations on allostatic load (1998).

A parallel approach to basic research should be taken by clinical approaches to stress during COVID-19, which integrates pertinent data to reach an all-encompassing consensus on basic mechanisms of action. In most cases, the onset of a medical condition is gradual and often begins with a few minor symptoms (Myin-Germeys et al., 2009; van Os et al., 2009). A narrow focus on individuals with overt clinical symptoms may be oversimplifying psychopathological outcomes associated with COVID-19. Subclinical and latent changes may have occurred even in people who do not qualify for diagnosis (Khan et al., 2020). It is possible that stress-related changes in brain function and structure are to blame for these symptoms. Prefrontal and limbic regions have previously been linked to chronic stress (Ansell et al., 2012; Berretz et al., 2021) and altered functional connectivity in frontoparietal brain circuits (Ansell et al., 2012). (Liston et al., 2009).

Magnet resonance imaging was used by Salomon et al. (2020) to study stress-related brain plasticity in Israel at an early stage of the pandemic (MRI). Prior to the pandemic’s outbreak, the researchers scanned healthy participants and compared their brain volumes to those of control participants scanned twice before the pandemic. Stress and anxiety-related neural circuits have increased in volume, according to Salomon et al. (2020). Importantly, these findings show that the pandemic of COVID-19 can affect the brains of those who have not been infected, and not just those who have been exposed to the virus (Crunfli et al., 2020; Lu et al., 2020).

Behavioral changes may also occur as a result of pandemic-related changes. For example, studies have shown that alcohol consumption has risen in some countries (Calina et al., 2021; Ingram et al., 2020). Individual health can be adversely affected and the risk of contracting COVID-19 and/or developing other physical or mental illnesses can be increased as a result of such maladaptive ways of dealing with stress (Gouin, 2011).

Basic stress research can complement epidemiological and clinical approaches to the COVID-19 pandemic by attempting to uncover subtle as well as severe alterations caused by adverse conditions. The HPA axis and the SNS are likely to play a role in the development of mental disorders if stress is a significant factor (Ehlert et al., 2001; Zänkert et al., 2019). The cost and time required to collect physiological markers such as saliva samples from large cohorts is prohibitive in large-scale population studies (Adam and Kumari, 2009; Friedman et al., 1988). Multiple physiological and neural stress markers can be assessed by basic stress research, which can help close this research gap. Laboratory research has been successful in identifying sources of intra-individual and inter-individual variability through a combination of comprehensive stress assessment and the fundamental strengths of laboratory research (e.g., control of confounding variables, standardization of experimental procedures). Taking these factors into consideration may help explain why some people are more susceptible to stress-related health issues than others (Epel et al., 2018; McEwen, 1998).

The question of whether chronic levels of increased stress affect acute stress processing is still being debated in relation to how COVID-19-related basic stress research may improve our understanding of human stress processing in general (Kudielka and Wüst, 2010; Lam et al., 2019; Matthews et al., 2001). Many studies show that chronic or cumulative stress can lead to a reduced stress response, which can be seen in a decreased sensitivity to acute stressors (Fries et al., 2005; Lam et al., 2019; Matthews et al., 2001; Sandner et al., 2020). There aren’t many systematic studies on this topic yet because it’s unethical to subject participants to chronic stress and risking their mental health just for research’s sake.

McEwen spent a lot of time talking about chronic stress (1998). Allostatic responses that are adaptive under normal conditions can be activated (1) too frequently, (2) too long, (3) not at all, or (4) without environmental adaptation were found in the laboratory by the researchers. A unique opportunity to learn more about the effects of chronic stress could arise if the COVID-19 pandemic causes the organism to exhibit one or more of these maladaptive response patterns.

Stressors that last for a long period of time and have no clear beginning or end are common in everyday life (Epel et al., 2018). As McEwen suggested, naturalistic stressors are similar to those conditions that lead to allostatic load (1998). It is therefore more ecologically relevant to investigate chronic stress rather than just its acute counterpart. As a field stressor relevant to the designated individual, COVID-19 adds another layer of ecological validity to the study (Rohleder et al., 2007). In light of the fact that basic stress researchers are typically restricted to artificially inducing stress in their experiments, it has been questioned how far laboratory findings can be applied in real-world scenarios (Johnston et al., 2008; Rohleder et al., 2007; Turner et al., 1990; van Doornen and van Blokland, 1992). COVID-19 is an excellent opportunity to measure stress in a field context because of the pandemic.

COVID-19 pandemic has been operationalized as an independent variable in ongoing experiments by some researchers who have already recognized this potential. Before the COVID-19 quarantine in Italy, Somma et al. (2021) collected data from behavioral tests that assessed the asymmetry of visual-spatial attention in a larger sample. They retested a subset of their participants several months later and found that quarantine had even more of a lateral effect on their test results. As can be seen, the COVID-19 pandemic had a significant impact on how people process visual-spatial data. There may be other cognitive and behavioral domains that may have been affected, as well as how these alterations may affect mental health in general, if further research is done.

The COVID-pandemic may not meet all quality criteria for experimental research despite its high ecological validity. Although the pandemic and other field stressors are not uniform stressors, they have numerous confounding variables (Amirkhan, 2021; Bueno-Notivol et al., 2021; Kowal et al., 2020). As a result, stress researchers must continue to rely on stress induction in the lab. Scientifically rigorous laboratory research has resulted in reliable experimental paradigms such as the Trier Social Stress Test that can be used to induce stress (TSST; Allen et al., 2017; Dickerson and Kemeny, 2004; Goodman et al., 2017; Kirschbaum et al., 1993). In the COVID-19 pandemic, these well-established protocols pose a significant challenge to stress researchers.

Stress research paradigms involving human participants are typically designed to expose them to situations that include elements of social evaluation. The social-evaluative aspect of a stressor is particularly important, compared to other aspects (Dickerson and Kemeny, 2004). The theory of social self-preservation explains its significance (Dickerson et al., 2004; Kemeny et al., 2004). Humans (as well as primates and other animals) aspire to maintain not only their physical but also their social well-being and status, according to this theory. The so-called social self-preservation system detects any threat to one’s social integrity and activates specific biological responses to counteract it. The HPA axis may be responsible for these physiological responses (Dickerson et al., 2004; Dickerson and Kemeny, 2004; Kemeny et al., 2004). A large portion of the ecological validity of laboratory stress-induction paradigms can be attributed to the fact that stress is primarily experienced in social contexts (von Dawans and colleagues, 2021).

Stress induction paradigms typically include some sort of social-evaluative threat, which is by definition most effective in human interactions, such as face-to-face social encounters. As an illustration, participants in the TSST complete a mock job interview and a series of difficult arithmetic problems while being evaluated by an anonymous panel of reviewers (Kirschbaum et al., 1993). Using the TSST as a model, researchers have demonstrated that stress induction can be made more effective by including explicit social-evaluative components (Kirschbaum et al., 1993). Also involving social evaluation are the Socially Evaluated Cold-Pressor Test (SECPT; Schwabe et al, 2008); the Simple Stress Procedure (SSSP); and the Maastricht Acute Stress Test (MAST; Le etal, 2020). (MAST; Smeets et al., 2012). Stress induction paradigms that rely on the social-evaluative element cannot be used during COVID-19 because of contact restrictions and home-based practices.

The social-evaluative component of established stress induction paradigms is what impedes their use in the context of the COVID-19 pandemic. It’s important to stress induction, even if we’ve already discussed experimental methods that don’t include it. This raises the question as to whether there is a need for research into stress induction without social-evaluative threats, or whether there are promising alternatives to the induction of psychosocial stress that could be used.

Recent research shows that it is possible to create social-evaluative threat by deviating from in-person social encounters between participants and panel. Using an invisible TSST panel, Andrews et al. (2007) demonstrated that stress reactivity could be achieved. Among other things, Düsing et al. (2016) found that replacing the panel with a video camera caused significant increases in cortisol levels. Furthermore, the authors of the study Düsing et al. (2016) hypothesized that their application of the TSST would cause cortisol concentrations to rise more subtly. Following the meta-analytic findings of Dickerson and Kemeny (2004), this is consistent with their findings. For example, this suggests that comparing differences in mean cortisol release does not take into account the sensitivity of cortisol reactivity. The social-evaluative component’s intensity, which can be altered in accordance with individual research proposals, may be a factor in the HPA axis’s reactivity (Andrews et al., 2007). In order to achieve significant cortisol reactivity for basic stress research, it may be desirable to use significant social-evaluative threat (feasible under the given circumstances).

As Labuschagne et al. (2019) argued, because the original TSST methodological description was so brief, it is likely that the paradigm will be different from laboratory to laboratory. Even though this could explain the variations in participants’ stress responses found in various labs and studies, the overall effectiveness of the TSST appears to be highly conserved. Because of this, future research should determine which procedural components are essential to the paradigm’s viability as well as which ones are optional or could be used as a target for further adaptations. According to Narvaez Linares et al. (2020), the number of panel members, as well as the number from which serial subtraction is started, can have an impact on the reliability and reproducibility of TSST applications in different laboratories.

Importantly, there are already research contexts in which participants and panelists cannot meet in person. Direct social confrontation is impossible to elicit social-evaluative threat in the MRI setting, which holds great promise for learning more about the neural mechanisms underlying stress processing (Noack et al., 2019). However, a number of different approaches to stress induction for neuroimaging in the scanner have been proposed (Berretz et al., 2021).

SET (e.g. Eisenbarth et al., 2016) asks participants to prepare for a speech that will be recorded and evaluated by people who aren’t there in person, for example. Under extreme time constraints, participants in the Montreal Imaging Stress Task (MIST; Dedovic et al., 2005) solve difficult arithmetic problems while receiving feedback on their average performance in comparison to that of other, hypothetical participants. ScanSTRESS (Streit et al., 2014) utilizes a panel located in the scanner’s control room as an additional feature. To provide individual (disapproving) feedback on the participant’s arithmetic performance, a live video feed is shown on the participant’s screen. The Minnesota Imaging Stress Test in Children uses a similar strategy for treating adolescents (MISTiC; Herzberg et al., 2020). Once they’ve had five minutes to prepare for the speech, participants are shown via live video feed while lying in the scanner and have to introduce themselves to the jury. Participants must then complete a multiple-choice arithmetic task as a follow-up. The arithmetic task in this paradigm can be scanned, but the speech task cannot because scanner noise interferes with the task. Furthermore, the motion artefacts associated with speaking would degrade the scanning quality. Preparation and delivery of an address in front of a pre-recorded panel is also required in the newly-developed Imaging Paradigm for Evaluative Social Stress (IMPRESS; Fehlner and colleagues, 2020).

Adapting established stress induction paradigms to new contexts is clearly suggested by these adaptations to contextual challenges. Laboratory stress research may find inspiration from MRI-based stress research because both settings have the same problem of in-person encounters inducing socially-evaluative threat being impractical.

For the MRI environment, different neuroimaging stress induction paradigms lead to overlapping but also distinct activations of different brain regions (Berretz et al., 2021). As a result, more research in this area is needed to determine which paradigm is best suited to each study’s objectives. Hence, determining whether a stereotypic neural stress response exists and how the discrepancies produced by various stress induction paradigms can be explained are critical steps to take in this direction (Berretz et al., 2021). Research on remote stress induction in the laboratory is being helped by approaches to social-evaluative stress induction that have been developed for use in MRI scanners.

Damian Jacob Markiewicz Sendler: Prior to the onset of the COVID-19 pandemic in the United States, a number of adaptations of the TSST were published that attempted to make it independent of physical panels (Helminen et al., 2019; Jönsson et al., 2010; Zimmer, 2019). Virtual reality and pre-recorded applications are two broad categories for these protocols. Evaluative threat is realized in both cases without any face-to-face social contact. The TSST-VR (virtual reality TSST) puts participants in front of computer-generated avatars rather than a live panel (Fallon et al., 2016; Helminen et al., 2019; Standard et al., 2020). As a result of the COVID-19 pandemic, fewer people are congregating in the laboratory, lowering infection risk. It’s also worth noting that there are some drawbacks to this approach. Cleaning and disinfecting potentially contaminated virtual reality devices, for example, is a necessity for experimenters. However, this panel is not presented in person or in real time, but rather in pre-recorded videos for TSST pre-recorded applications (DeJoseph et al., 2019; Hawn et al., 2015; Smith et al., 2020). Below you’ll find more information on the procedural aspects of TSST-VR and pre-recorded versions, as well as details on effect sizes.

It has been a major goal in many other research fields to adapt both experimental paradigms and therapeutic interventions to virtual reality (Emmelkamp, 2005; Lohse et al., 2014; Slater, 2009). Computer-generated sensory input is used in virtual reality to create the illusion of operating in real-world scenarios that are sufficiently similar to physical experience (Fallon et al., 2016). To activate the brain’s schema-based system, only minimal computer-generated information is needed to activate a system for imagining real-world scenarios in terms of schemas, resulting in the activation of a system that encodes imaginations of real-world scenarios in terms of schemas (Diemer et al., 2014; Parsons and Rizzo, 2008). In this way, even a virtual panel debate should invoke social norms (Zimmer et al., 2019).

According to Helminen et al. (2019) on 13 studies using different versions of the TSST-VR, this procedure generally serves to successfully induce stress, as indicated by a significant cortisol response, which was found to be the case in all 13 studies. There was an average size of this effect of 0.65, which suggests that the cortisol response caused by the use of the TSST-VR was smaller than previously thought, even though it was statistically significant. A small effect size is more typical in the standard TSST when measuring cortisol levels. Allen et al. (2014) and Goodman et al. (2014) both use d = 0.925 as a rough approximation (2017). Two studies that directly compare the use of the Tactile Sensory Stimulation (TSST) in virtual and real-world environments support this conclusion. Despite this, because the virtual and original TSST cortisol reactivity patterns are so similar, the authors came to the conclusion that the TSST-VR is just as effective as the original TSST.

Achieving the desired stress response may be contingent on technology’s ability to provide a realistic sense of presence in the virtual environment (Jönsson et al., 2010; Montero-López et al., 2016). Because of this, one would expect that the more input is derived from virtual reality (ie, more immersive the paradigm), the stronger emerges the feeling of being involved and spatially present within this virtual world (Slater, 2009). Effect sizes in individual studies were found to be affected by the virtual environment’s immersion in Helminen et al. (2019), among other factors. These researchers compared studies that used high and low levels of virtual reality immersion and found that the mean effect sizes of the studies that used higher levels of virtual reality immersion were significantly larger. In light of these considerations, it appears to be preferable to use CAVE systems or head-mounted displays (Helminen et al., 2019).

Damian Sendler

Damien Sendler: In addition to a lack of immersion, participants suffer when they take on the role of “observer” rather than “participant” in the scene. However, low interactivity may severely diminish the experience of social-evaluative threat (Fallon et al., 2016; Jönsson et al., 2010), even though this aspect was not examined in its influence on the effect sizes of individual studies in the meta-analysis by Helminen et al. (2019). TSST-VR avatars that represent the panel have been programmed to show subtle gestures to avoid this. An experimenter who is not visible to the participant typically controls these movements and other interactive features. Avatar behavior can be matched with participant performance in this way, allowing for some sort of interaction to be taken into account. This has been shown to be possible in several studies, including those by Fallon et al. in 2016 and by Fich et al. in 2014. To give their panel a voice, some protocols use pre-recorded audiotapes in addition to the situational flexibility provided by the panel members’ nonverbal appearance (Jönsson and colleagues, 2010; Santl and associates, 2019; Shiban and associates, 2016).

Psychological (stress) research could benefit greatly from the use of smartphones in addition to online applications (Miller, 2012). Several apps have been developed for use by patients in this context. According to Wisniewski et al (2019), for example, an entire battery of simplified neuropsychological tests appears in the form of “games”. Lam et al. (2021) used smartphones to monitor cognitive functioning in multiple sclerosis (MS) patients using an app-based version of the Symbol Digit Modalities Test (SDMT) (SDMT; Smith, 1982, 1968). Considering that the apps in both studies could be used in healthy subjects to address non-clinical research questions, it is possible to do so. The iDichotic app (Bless et al., 2013), a smartphone-based implementation of the dichotic listening task, was already intended to have a wider application. Participants from all over the world have used this app to great effect in research on language lateralization using this app (Beste et al., 2018; Ocklenburg et al., 2016; Schmitz et al., 2018).

Given the ease with which a TSST-OL can be run on a smartphone’s video communication software, it appears that stress induction via smartphone is possible. Smartphones may have an advantage over laptop computers in terms of portability when compared to online adaptations. If you have a small screen, this could be a problem A minimum screen size of 13 inches was required for inclusion in the study conducted by Gunnar et al. (2020).

Despite this, mobile apps allow for a greater number of samples to be collected than online versions (Bless et al., 2013). Furthermore, smartphone-based research can be carried out without the presence of an experimenter. Torous et al. (2020) also emphasized this viewpoint, focusing on the COVID-19 pandemic. An app-based approach to telehealth is needed in the current climate of crisis, according to these authors. Researchers may see this as a positive development because it greatly enhances data accessibility and scalability (Torous et al., 2020).

It is possible that stress researchers could lose out on the benefits of unlimited scalability due to the fact that stress research studies typically require a more in-depth assessment of variables whose quality could be compromised. Stress should not only be measured by behavioral or self-reported parameters, as is widely accepted (Dickerson and Kemeny, 2004; Epel et al., 2018). To that end, the following paragraphs will discuss methods for ensuring accurate measurement of stress markers in newer iterations of tried-and-true stress induction procedures.

The reliable measurement of stress markers is an important consideration when evaluating new approaches to stress induction (Harvie et al., 2021). It is common to use questionnaires or other self-report methods (Epel et al., 2018) to assess the subjective psychological component of the stress response. These methods can easily be applied to procedures like the TSST-OL. Self-reported data can be collected via a shared link using online survey software, which can be used on any device with a stable internet connection to obtain subjective stress measurements during video calls.

Enhanced self-reporting techniques, such as ecological momentary assessment, may be made possible by mobile devices like smartphones (EMA). There are a plethora of methods that can be used to collect real-time information about an individual’s ecological context using EMA (Shiffman et al., 2008). EMA is capable of registering random fluctuations in individual stress levels at (random or predetermined) time intervals for stress research (Kudielka et al., 2012; Schlotz, 2011; Shiffman et al., 2008). Using smartphone stress questionnaires, Sicorello et al. (2020) recruited participants over the course of several days. Besides that, they kept a close eye on the circumstances surrounding the changes they noticed. Study participants’ susceptibility to external events is influenced by a gene variation in serotonin transporter. Additionally, EMA can be used by researchers to monitor individual stress levels in relation to a specific stressful event (event-based monitoring) in a systematic manner (Shiffman et al., 2008). Using a smartphone-based longitudinal EMA approach, Huckins et al. (2020) found a correlation between the COVID-19 pandemic and an increase in symptoms of anxiety and depression in a student sample.

Physiological stress markers may be assessed as a result of these approaches. In addition to saliva samples, other stress markers like heart rate or blood pressure can be recorded with EMA, which includes everything from written self-reports to phone interviews to physiological assessments using sensors (Harari et al., 2016; Shiffman et al., 2008; Wang et al., 2014). (Anjum et al., 2011; Foody et al., 2014; Steptoe et al., 2007). Instead of sending participants home with their own ambulatory cardiac hardware and having it returned, Eagle et al. (2021) chose to send ambulatory cardiac hardware that was not associated with EMA for the purpose of measuring sympathetic parameters. Polar and Apple watches (e.g., Hernando et al., 2018) and heart rate chest straps (e.g., Jentsch and Wolf, 2020) have been used by other researchers to track a variety of activity parameters in larger samples (Wang et al., 2017).

Furthermore, these methods require additional sensors or even invasive devices to be used in order to work (Ciman and Wac, 2016). Portable or even wearable, these devices can be used outside the laboratory, but they still need to be purchased and shipped. The devices must therefore be computer or smartphone-based in order to facilitate widespread use. It was Harvie et al. (2021) who first recognized this opportunity in a TSST-OL variant by measuring heart rate variability in addition to self-reported stress on a smartphone with appropriate software. According to an increasing body of literature, there is a debate about whether smartphones’ built-in software or sensors should be used to collect information about people’s behavioral and lifestyle patterns (Can et al., 2019; Garcia-Ceja et al., 2016; Harari et al., 2016; Miller, 2012). Individual behavior can thus be characterized using smartphone sensor data, which can be used to perform so-called digital phenotyping (Wisniewski et al., 2019).

Damian Jacob Sendler

Additionally, it appears that measuring HPA axis-related endocrine parameters is feasible. For stress research, saliva samples are typically requested to extract cortisol. There is a simple method to collect data from participants using online stress paradigms. When Gunnar et al. (2020) decided to mail saliva collection materials to their participants’ homes, they left it up to the participants to return the materials once the study was over. Furthermore, this was not a brand-new idea at the time. CARDIA (Coronary Artery Risk Development in Young Adults) was a study conducted decades ago by Friedman et al. (1988). Non-frozen mailed samples of cortisol have been shown to be relatively stable or at least can be assumed to survive a regular postal delivery taking a few days at room temperature (Garde and Hansen, 2005). In order to ensure the quality of the data, it appears that participants must be well-trained on how best to collect saliva samples (Adam and Kumari, 2009; Lucas et al., 2019).

Alpha amylase, which is an indirect indicator of sympathetic activation, can be retrieved from saliva (Nater and Rohleder, 2009). Gunnar et al. (2020), on the other hand, measured both alpha amylase and cortisol from samples collected at home and mailed to the laboratory. There are currently no studies systematically verifying the stability of alpha amylase in non-frozen samples or under thermal constraints. Salivary alpha amylase appears to be stable for at least five days at room temperature, however (O’Donnell et al., 2009).

Stress hormones can be measured by analyzing saliva samples in non-laboratory settings, as demonstrated by this study. This means that online or smartphone-based stress induction procedures don’t eliminate the possibility of assessing all central stress markers to determine whether a particular stress exposure was successful or not.

Yet another advantage is provided by stress induction paradigms that are not restricted to the confines of a research lab setting. Samples that cannot be obtained locally or that are difficult to test using standard stress induction procedures can be accessed through these methods. Older adults with limited mobility space, bedridden, or homebound people can be assessed using online applications if they are easy to use and do not require extensive digital technology experience (Jeon and Dunkle, 2009; Osmanovic-Thunström, 2015; Chanproong et al., 2016; Ornstein et al., 2015; Qiu et al., 2010). Furthermore, home-based stress research allows for access to specific patient groups, such as those with neurodegenerative diseases like MS, for which stress systems have been linked to pathogenesis and progression (Gold et al., 2005). For these patients, previous research has established online tools or automatic internet-based programs for therapeutic purposes (Fischer et al., 2015). As a result of the COVID-19 pandemic, demand for these services has increased even more. Examples include a review of various tools used in what is known as “tele-neurology,” which focuses on neurological examinations of patients with Multiple Sclerosis (MS) using video-based or digital technology in general by Moccia et al. (2020).

When it comes to stress research, online applications have set new standards because samples from all over the world are more accessible as long as they have access to a specific device with an internet connection. Few studies have compared the stress levels and coping abilities of Scottish and Australian (Pithers and Soden, 1998) or Turkish and Macedonian teachers (Eres and Atanasoska, 2011) to date. Berry et al. (1987) conducted a literature review on the effects of acculturative stress on immigrants, refugees, and other members of ethnic minorities in Canada. These early studies, however, only used questionnaire methods to assess stress. A more in-depth assessment can be made using modern technology and the stress procedures discussed in Section 4. For example, a TSST-OL could be conducted online by people from all over the world. According to Dufau et al. (2011), new technologies have the potential to revolutionize cognitive science by making it possible to collect data from participants all over the world using appropriate devices. Consequently, sampling biases due to the need for participants to visit designated research facilities and natural homogeneity among study participants can be overcome.

Another possibility is the development of new screening standards for specific samples. There are still many unanswered questions about individual differences in stress responsiveness in general. Researchers could collect preliminary data from large samples using online stress experiments, and then invite only a subset of individuals who meet specific predefined criteria to the laboratory for further testing (Parker et al., 2020). Systematic and precise investigation of people with blunted and raised stress-related cortisol responses, for example, may be made possible by this.

Virtual reality and pre-recorded or online applications of stress induction paradigms allow for new experimental variations during the current COVID-19 pandemic. With regard to methodological considerations, the TSST-VR or prerecorded variations promote standardization and resource utilization (Fallon et al., 2016; Zimmer et al., 2019). TSST-VR and TSST-OL open up new avenues for stress research by allowing key stress components to be implemented in ways that were previously unimaginable. These methods may be able to accomplish two things at once. It’s possible to alter the actual procedure’s level of stress, for example. In contrast, they would allow for systematic manipulation of the variables that determine the magnitude of a triggered stress response to be determined.

The current COVID-19 pandemic has a long-term impact on mental health and well-being, and it is imperative to conduct epidemiological, clinical, and basic stress research to better understand this effect. The COVID-19 pandemic serves as a catalyst for rethinking the use of social-evaluative components in established stress induction paradigms. We’ve come to the conclusion that the TSST can benefit from a variety of modifications based on the various tools and technologies at our disposal. Beyond the COVID-19 pandemic, new approaches to stress research will be beneficial. These will make it easier to conduct studies with participants who are confined to their homes or have limited mobility. Finally, they offer new avenues for experimentation in terms of adaptability to individual research objectives, as well as new perspectives on experimental variation.

Dr. Sendler

Damian Jacob Markiewicz Sendler

Sendler Damian Jacob

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