The manifestations of stress are diverse and culturally and individually determined, but it is present in every culture, every socioeconomic level and – it is global. Introducing a special BJPsych Advances issue on stress, this editorial outlines research questions to be examined and first actions to be taken in the multidimensional sphere of stress, highlighting the need for a collaborative interdisciplinary approach in both research and practice.

Stress-related disorders are diverse and they may be mental and physical. Often, several body systems and organs are involved simultaneously. The pathophysiology of stress-related disorders involves many factors: an observable or perceived stressor, an individual dynamically evolving vulnerability and maladaptation leading to imbalance, as well as environmental, cultural, gender and life-cycle variables. There is a need to develop a comprehensive quantifiable stress assessment instrument. It would be based on the ‘stress factor’, a dimension that would integrate biological, psychological, social, economic and spiritual parameters and would allow for cultural sensitivity. It would contribute to clinical operational sophistication and would illuminate treatment options and multidimensional well-being interventions. Hopefully, it would facilitate development of culturally sensitive pharmaceutical or biophysiological adaptogens and homeostatic interventions.

Stress is the most important proximal precipitant of depression, yet most large genome-wide association studies (GWAS) do not include stress as a variable. Here, we review how gene × environment (G × E) interaction might impede the discovery of genetic factors, discuss two examples of G × E interaction in depression and addiction, studies incorporating high-stress environments, as well as upcoming waves of genome-wide environment interaction studies (GWEIS). We discuss recent studies which have shown that genetic distributions can be affected by social factors such as migrations and socioeconomic background. These distinctions are not just academic but have practical consequences. Owing to interaction with the environment, genetic predispositions to depression should not be viewed as unmodifiable destiny. Patients may genetically differ not just in their response to drugs, as in the now well-recognised field of pharmacogenetics, but also in how they react to stressful environments and how they are affected by behavioural therapies.

Exposure to acute versus chronic stressors and threats activates the immune system in adaptive and maladaptive manners respectively. Chronic activation arising from persistent stress exposure can contribute to an inflammatory response in the periphery and in the brain that has been implicated in stress-related psychopathology, including depression and anxiety. We review the immunology of acute and chronic stress exposure, integrate this discussion with the emerging literature linking heightened immune activation and inflammation to mood and anxiety disorders, and consider the translational implications of the immune system's role in these psychiatric conditions, with a brief overview of potential interventions.

Resilience is broadly defined as the ability to bounce back from adversity or trauma. Recent advances in resilience research have shifted away from merely describing individual characteristics towards focusing on the complex interactions between individuals and their dynamic personal, community and cultural contexts. It is clear that resilience involves both neurobiological and cultural processes. Neurobiological contributions include genes, epigenetics, stress-response systems, the immune system and neural circuitry. Culture helps to elucidate collective systems of belief and accepted positive adaptations. Importantly, resilience can also be affected by evidence-based interventions and deliberate practice on the part of the individual. This review seeks to understand resilience as a complex and active process that is shaped by neurobiological profiles, developmental experiences, cultural and temporal contexts, and practical training. It uses the COVID-19 pandemic as a case example to better understand individual and group responses to tragedy. We suggest practical recommendations to help populations around the world cope and recover from the global threat of COVID-19.

The differentiation of pathological stress responses from responses that are appropriate and adaptive is a challenge with little to guide the clinician. This refreshment considers adjustment disorder and possible approaches to distinguishing those who have the disorder from those who are responding ‘normally’ to stressful events.

As experts in disaster mental health push to reframe disaster response as a preventive medicine rather than its actual state of acute management, various factors should be considered. Although a whole population may be victim to the effects of disasters, particularly vulnerable are those with severe mental illness. Therefore, efforts geared to bolster trauma response should centre on these individuals, starting at a community level and reaching organisational and governmental endeavours and funding.

Post-traumatic stress disorder (PTSD) is a common trauma and stressor-related disorder. Trauma-focused psychotherapies and selective serotonin reuptake inhibitors represent current state of the art treatment for PTSD, with current evidence favouring psychotherapy as first-line treatment. Much room remains for development of more effective therapeutics. This article give a brief update on diagnosis and treatment of PTSD.

It is generally believed that the physiological consequences of stress could contribute to poor outcomes for patients being treated for cancer. However, despite preclinical and clinical evidence suggesting that stress promotes increased cancer-related mortality, a comprehensive understanding of the mechanisms involved in mediating these effects does not yet exist. We reviewed 47 clinical studies published between 2007 and 2020 to determine whether psychosocial stress affects clinical outcomes in cancer: 6.4% of studies showed a protective effect; 44.6% showed a harmful effect; 48.9% showed no association. These data suggest that psychosocial stress could affect cancer incidence and/or mortality, but the association is unclear. To shed light on this potentially important relationship, objective biomarkers of stress are needed to more accurately evaluate levels of stress and its downstream effects. As a potential candidate, the neuroendocrine signalling pathways initiated by stress are known to affect anti-tumour immune cells, and here we summarise how this may promote an immunosuppressive, pro-tumour microenvironment. Further research must be done to understand the relationships between stress and immunity to more accurately measure how stress affects cancer progression and outcome.

Complementary and integrative medicine provides safe, low-cost, effective treatments for conditions ranging from everyday stress to post-traumatic stress disorder. The evidence for herbs, nutrients and mind–body practices is growing, despite disproportionately small amounts of financial support compared with funding for expensive pharmaceuticals. The unsustainable cost of conventional treatments, the moral imperative to care for millions of uninsured and the impact of COVID-19 compel us to fully explore known and potential benefits of treatments being used by complementary and integrative practitioners.

The worldwide stress that is a consequence of the COVID-19 pandemic illuminates the need for mental preventive actions. Such ‘mental vaccines’ should be interdisciplinary and culturally sensitive. They should enhance resilience and adaptation of communities as well as vulnerable individuals.

The problem of occupational stress in healthcare workers is hardly new, but effective interventions in this area are lacking despite being sorely needed – especially in the ongoing COVID-19 pandemic. The results of a Cochrane review suggest that cognitive–behavioural therapy and mental and physical relaxation reduce stress more than no intervention but not more than alternative interventions, and that changing work schedules may lead to a reduction of stress. Other organisational interventions showed no effect on stress levels. However, the evidence is of low quality owing to risk of bias and lack of precision. This commentary critically appraises the review and attempts to put its findings into the current real-world context.