Questions in need of answers

The pandemic-induced stress illuminates the globalised vulnerability to stressors as well as the impact on all levels of society: international, national, local communities, interest groups, families and individuals. It also demonstrates the diversity of responses, from unifying to divisive, from victimisation to altruistic heroism, from resilience to collapse of all systems, from hope to despair. The differences raise questions that are in need of operationalised solutions:

• • Why do some societies respond to threats with unity and productive actions while others disintegrate?

• • What is the role of leadership, how should it be executed and when?

• • What is the optimal stress-reducing balance between individuals’ self-interests and benefits to society?

• • How can we prevent or reduce the next crisis? What are the financial, social and emotional costs of that prevention?

• • Is there a community post-traumatic stress disorder (C-PTSD)? Can it be prevented?

• • Why do some individuals, and societies, perceive an event as traumatic and respond with PTSD while others are resilient and even strengthened?

• • Can stress be eliminated? Can community resilience be enhanced? How?

On a clinical public health level:

• • Can vulnerable populations be identified prior to a crisis? This is important especially in places where disasters are so frequent that they are a predictable part of life, such as regions prone to floods, hurricanes, and violent tribal or border conflicts.

• • Can vulnerable individuals – those with low resilience – be identified within the vulnerable population?

• • Can a cost-effective easily accessible mass-produced biological test for low resilience and stress be developed?

• • Are there gender differences in stress responses? Why?

• • Are there ethnic differences in resilience? Can they be distinguished from socioeconomic factors? Should they be?

The list of stress-related questions is almost endless. Indeed, as in any productive investigation, elaboration of one question opens the door to new ones. What is apparent is that operational knowledge of stress should be multidimensional and interdisciplinary. It should be integrative and comprehensive, acknowledging the complexity and applying innovative approaches to make it seem ‘simple’ and achievable.

Essentially, we should move from multiple separate ‘focused’ fields to a well-rounded multidimensional sphere of stress.

Tackling the multidimensional sphere of stress

As an essential step to understanding and combating stress and stress-related disorders there is a need for interdisciplinary collaborative partnerships (Halbreich Reference Halbreich, Schulze and Botbol2019). It is not only that stress is global – the sphere of stress is multidimensional and should be conceptually and practically well-rounded. A unidimensional field in which point A influences adjacent point B would not provide for a relevant operational answer because each change in the systems induces many other changes, and not all of them can be predicted or controlled.

As has been demonstrated by the COVID-19 pandemic, a change in one health parameter may cause profound changes in the economy, infrastructure, social services systems, interracial relationships, international relations, technological priorities and politics (among many other areas). Therefore, interdisciplinary partnerships are needed at a conceptual level as well as a very practical problem-solving level. This creates a management problem. Such interdisciplinary groups are routinely managed in for-profit corporations, where a product requires input from professionals with diverse expertise. Interdisciplinary groups should also be established in the public-benefit sector. Not-for-profit interdisciplinary task forces could learn from the input of business executives, who might even be integral partners of the group. An academic–industry–government cooperation might be an intriguing structure that could create sufficient incentives to overcome political and control obstacles. At first the interdisciplinary group might function as an advisory board, discussing the conceptual issues and their ramifications for planning. The planning would involve increasing levels of management and political considerations, leading to operational teams.

An initial minimally controversial issue might be screening for vulnerable populations. This epidemiological exercise would assess parameters such as gender, age, income, education, housing, occupation, employment, health indicators and other socioeconomic parameters. Epidemiological population-based screenings are very important in developing and emerging economies but the consequences of the COVID pandemic suggest their importance in established economies as well.

It is hypothesised that vulnerable populations would include pregnant women, very-low-income and poverty-stricken neighbourhoods, high-density urban housing and locations experiencing repeated recent disasters. Minorities and immigrants may also be more vulnerable to the consequences of stress. However, initial epidemiological studies of stress should be broad enough to uncover unexpected segments of the general population.

An important question with a needed and possible solution is: Once vulnerable populations, situations and locations are identified, who are the individuals with low resilience, whose resilience should be enhanced, and who are the people with high resilience who may be trained to be first responders?

A straightforward subsequent question with a complicated set of answers is: What makes an individual vulnerable to negative consequences of stressful events? Geneticists are making a good progress on that question, continuously demonstrating genes that are involved in mental symptoms in general or in specific symptoms (Caspi Reference Caspi, Houts and Belsky2013). However, epigenetics plays an important role, and this change may be transferred across generations (Yehuda Reference Yehuda and Lehrner2018). An intriguing question that is still to be answered is whether epigenetics is cumulative through many generations. If so, is there a genetics of social history? Is a long history of oppression and discrimination or slavery inducing scars that last for generations? What is, or are, the interfaces between genetics, epigenetics, environment, economy and perceptions?

Furthermore, inflammation has been shown to be important in the processes of stress responses. How is it transferable? Being demonstrated across several stress-related disorders, is the hereditary chain specific to a certain organ or body system? Or might it be expressed as a particular stress-related disorder in one generation, but have a different expression in another? A similar question is pertinent to autoimmune disorders. Here the contribution of the environment is of importance because even within the same individual, symptomatic expressions may vary in different locations and at various life stages.

The contribution to and involvement of multiple hormonal systems in stress and stress responses is beyond doubt. However, several unsolved questions should be confronted. First, what is the contribution of gonadal hormones to sex differences (if there are any) in stress responses? Are any such differences related to the interactions between brain stress mechanisms and gonadal hormones, especially oestrogen? These interactions are well-documented in animals and humans (e.g. Bangaser Reference Bangaser, Eck and Sanches2019; Goldstein Reference Goldstein, Tuben and Foster2019) but are they also gender-related, incorporating the sociocultural aspects of being a man or a woman and what is expected of each one?

Another presumption is that some hormones may be biomarkers for stress – in particular, elevated levels of cortisol have been considered. However, in my opinion no specific hormonal marker of distress has been confirmed so far. This is an important issue in the development of biological and physiological tests and diagnostic aids for elucidation of stress and stress-related disorders in humans.

‘All is predetermined, but the choice is given’

In the multicultural context of stress, spirituality should be added to the equation. As early as Biblical times a sage declared that ‘all is predetermined, but the choice is given’. Fate is not definitively determined by genetics, epigenetics, inflammation, economy, birth and beliefs. Vulnerability is just that – vulnerability. Each individual (and society) has a choice how to handle his/her/our vulnerability and take appropriate actions.

What are the ‘appropriate actions’? First, a change of attitudes is needed. Conventional thinking and approaches would not lead us far enough. The articles in the current issue of BJPsych Advances demonstrate that we know many facts about stress and its consequences. Clinicians can apply them in day-to-day practice. However, we should realise that question marks outweigh exclamation marks. To get deeper into the sphere of stress we should try to know what we do not yet know and fill some of the gaps with open minds and innovative approaches. This is especially important for prevention of the consequences of stressors. To construct efficacious preventions of an unknown event or a predictable event whose timing may be surprising, flexibility of mind and adaptable actions are a must. Change is inevitable, and we should not be overwhelmed by it.