International study of the Complex Stress Reaction Syndrome: Implications for transdiagnostic clinical practice

BACKGROUND: The debate regarding diagnostic classification systems in psychiatry (categorial vs dimensional systems) has essential implications for the diagnosis, prevention and treatment of stress reactions. We previously found a unique pattern of stress reaction in a study executed during the coronavirus disease 2019 pandemic using large representative samples in two countries, and termed it the Complex Stress Reaction Syndrome (CSRS). AIM: To investigate CSRS, Type A (psychiatric symptoms, spanning anxiety, depression, stress symptoms, and post-traumatic stress disorder (PTSD)), with or without long-coronavirus disease (COVID) residuals (CSRS, Type B, neuropsychiatric symptoms spanning cognitive deficits and fatigue, excluding systemic symptoms). Our two-tailed hypothesis was that CSRS is a condition related to an unrecognized type of stress reaction in daily life in the general population (Type A) or that it is related to the severe acute respiratory syndrome coronavirus 2 infection and its long-COVID residuals (Type B). METHODS: 977 individuals in four continents (North America, Europe, Australia and the Middle East) completed the online study questionnaire in six languages using the Qualtrics platform. The study was managed by six teams in six countries that promoted the study on social media. The questionnaire assessed anxiety, depression, stress symptoms and PTSD (CSRS, Type A), cognitive deficits and fatigue (CSRS, Type B). The data were analyzed using Proportion Analyses, Multivariate Analysis of Co-Variance (MANCOVA), linear regression analyses and validated clinical cutoff points. RESULTS: The results of the Proportion Analyses showed that the prevalence of 4 symptoms spanning anxiety, depression, stress symptoms, and PTSD was significantly higher than the most prevalent combinations of fewer symptoms across 4 continents, age groups, and gender. This supports the transdiagnostic argument embedded in the CSRS (Type A). The same pattern of results was found in infected/recovered individuals. The prevalence of the 4 psychiatric symptoms combination was significantly greater than that of 5 and 6 symptoms, when adding cognitive deficits and fatigue, respectively. MANCOVA showed a significant three-way interaction (age × gender × continent). Further analyses showed that the sources of this three-way interaction were threefold relating to two sub-populations at-risk: (1) Individuals that self-identified as non-binary gender scored significantly higher on all 4 psychiatric symptoms of the CSRS, Type A at young age groups (< 50 years old) in North America compared to (self-identified) women and men located in the 4 continents studied, and to other ages across the adult life span; and (2) This pattern of results (CSRS, Type A) was found also in women at young ages (< 40 years old) in North America who scored higher compared to men and women in other continents and other ages. Linear regression analyses confirmed the MANCOVA results. CONCLUSION: These results show a combined mental health risk factor related to stress reactivity, suggesting that the CSRS is sensitive to populations at risk and may be applied to future identification of other vulnerable sub-populations. It also supports the transdiagnostic approach for more accurate prevention and treatment. Time will tell if such transdiagnostic syndromes will be part of the discussions on the next revisions of the traditional classification systems or whether the crisis in psychiatry further evolves.