Reconsidering Persistent Somatic Symptoms: A Transdiagnostic and Transsymptomatic Approach

Abstract

Regardless of cause, persistent somatic symptoms (synonymous with persistent physical symptoms) are distressing somatic complaints, which are present on most days for at least several months [1]. The term “persistent somatic symptoms” is therefore not linked to a specific cause of complaints; it is not a diagnosis, but a description of a condition based on clinical features. Persistent somatic symptoms, like any other symptoms, will always correspond to the subjective reality of the person experiencing them; no biomarker will be able to define this subjective experience. Although the term persistent somatic symptoms is aetiology-free in the literal sense, it is still very often misunderstood to be limited to functional somatic disorders, somatic symptom disorders, or so-called “medically unexplained symptoms,” the latter term in itself being highly problematic for both scientific and stigmatization reasons [2‒4]. This misunderstanding of persistent somatic symptoms reflects an unfortunate and scientifically outdated dualism of mind and body and does not do justice to the complexity and current scientific knowledge of symptom perception and biopsychosocial explanatory models. Of course, persistent somatic symptoms occur within somatic diseases, functional somatic disorders, mental disorders, and undiagnosed diseases [1]. In some cases, a somatic disease is the trigger for persistent somatic symptoms, which then may persist even after successful treatment of the somatic disease [5, 6].Explanatory models for diverse persistent somatic symptoms such as pain, fatigue, gastroenterological, or neurological symptoms [1, 7, 8] have at least one feature in common: they usually involve biological, psychological, and social mechanisms and risk factors, i.e., they are biopsychosocial models. From this perspective, “transsymptomatically,” there are similarities but also differences in the postulated factors and mechanisms involved in the development of the various symptoms. Similarly, “transdiagnostically,” there are both commonalities and disease-specific factors and mechanisms for the development of the same persistent symptom in different diseases, such as fatigue in multiple sclerosis [9], post-stroke [10, 11], heart failure [12], inflammatory bowel disease [13], rheumatoid arthritis [14], or chronic fatigue syndrome [15]. In particular, factors of a psychosocial nature that contribute to symptom perception are likely to be common across diagnoses [1].The aim of this editorial is to explore the possibilities of a transdiagnostic and transsymptomatic approach to persistent somatic symptoms, as based on the current state of science. The potential of such a transdiagnostic and transsymptomatic approach lies in achieving synergies in terms of science, understanding, and treatment of those affected.A transsymptomatic perspective on functional somatic disorders was proposed many years ago [16]. We take up this perspective and extend it transdiagnostically to also include bodily complaints in somatic diseases. What are the reasons for adopting a transdiagnostic or transsymptomatic perspective on persistent somatic symptoms? First and foremost, as outlined below, scientific evidence on symptom perception and biopsychosocial mechanisms suggests that in addition to disease-specific factors, there may be a high degree of commonality in the genesis of different persistent symptoms across diseases.Current models of symptom perception, informed by experimental and neuroscientific research, propose that symptom perception operates through predictive coding [17, 18]. Predictive coding means that the brain minimizes discrepancies (prediction errors) between unconscious predictions of bodily states and incoming sensory signals. This error minimization process is guided by the relative reliability of both the implicit (i.e., mostly unconscious) priors and actual incoming bodily signals and eventually results in actual experience of a symptom [17, 18].For newly emerging and often strong somatic input, such as those caused by an acute infection, predictive coding models explain that symptom perception is primarily shaped by sensory input from the periphery, given the lack of strong prior predictions for new, unexpected symptoms. Predictive coding models also elucidate why persistent somatic symptoms can persist in the absence of ongoing sensory input [19]: For instance, persistent pain may be increasingly driven by strong implicit predictions based on an individual’s extensive history of suffering: As the strength of the somatic input decreases, such as when the initial inflammation has healed and peripheral sensory signals have ceased, the influence of implicit predictions becomes stronger. Placebo and nocebo effects, which are good examples of somatic symptoms in the absence of sensory input, can also be well explained by strong implicit predictions within predictive coding models [1].It is important to note that disease-specific factors, such as personal illness experiences and structural or pathophysiological disease processes, contribute to the relative balance of prior predictions and the generation of sensory input. However, the eventual perception of somatic symptoms results from an unconscious integration of prior predictions and sensory input, with the experiencing person unable to discriminate the relative contribution of the two sources of information. Importantly, the process of predictive coding in the perception of somatic symptoms is a generic model that applies to all symptoms and diseases. The extent to which symptoms are related to pathophysiological processes in the body is, in this view, a matter of degree that can vary depending on the characteristics of the somatic input, the person, and the context. In most conditions, there will be a close relationship between symptoms and biomarkers of pathophysiological processes, but in some conditions, this relationship may be weaker or even absent. Thus, predictive coding models strongly advocate that persistent somatic symptoms be considered transdiagnostically and transsymptomatically.Scientific studies across various clinical conditions have demonstrated that biological, psychological, and social factors all play crucial roles in the persistence of somatic symptoms [20]. Conceptual biopsychosocial working models for the persistence of somatic symptoms have recently been developed on the basis of the factors known to date [1, 21]. A strength of these models, which include predisposing, triggering, maintaining, and aggravating factors for symptom persistence, is that they can be empirically tested. Research thus far identified certain risk factors for persistent somatic symptoms that transcend specific diagnoses and symptom presentations. For example, depression has emerged as a significant risk factor across almost all studies [1, 9, 10, 12‒14]. Other research highlights the role of anxiety-related factors, such as symptom focusing, catastrophic thinking, somatosensory amplification, and illness-related anxiety, in the persistence of somatic symptoms [1, 15, 22, 23]. Many other risk factors, such as adverse childhood experiences and dysfunctional symptom expectations, are also known to contribute to the persistence of somatic symptoms [19, 24, 25]. While each of these factors tends to have a significant impact on the persistence of symptoms, there is likely to be a high degree of overlap between these factors, necessitating future research to identify their core elements. A potential common ground of many of these factors is that they are – implicitly or explicitly – a source of strong priors.Emerging evidence within the framework of biopsychosocial models suggests that frequently identified risk factors for persistent somatic symptoms, such as depression, illness-related anxiety, or adverse childhood experiences, are not specific for individual symptoms or diseases – although their impact may vary depending on the overall constellation of risk factors. This evidence on the role of biopsychosocial determinants of persistent somatic symptoms suggests that a transdiagnostic and transsymptomatic approach could yield significant synergies and mutual learning effects. Obviously, disease-specific pathophysiological mechanisms should be addressed in the treatment wherever possible [1]. At the latest when symptoms persist despite adequate biomedical treatment of pathophysiological and structural causes, additional psychosocial mechanisms need to be considered in the development and treatment of persistent somatic symptoms. However, it is certainly preferable to address psychosocial mechanisms earlier in order to reduce the risk of developing persistent somatic symptoms and to intervene preventively. Finally, if persistent somatic symptoms are seen as the result of biopsychosocial mechanisms and their interactions, and if medicine is not reduced to biomedical mechanisms, the distinction between “medically explained” and “medically unexplained” becomes irrelevant anyway [2, 4]. Consequently, it is imperative that biopsychosocial models become more integrated into both medical practice and scientific research, incorporating not only biomedical but also psychosocial components to provide a more comprehensive understanding and treatment of persistent somatic symptoms.An example of transdiagnostic and transsymptomatic research into the aetiology of persistent somatic symptoms is the SOMACROSS research unit (“Persistent Somatic Symptoms across Diseases: From Risk Factors to Modification,” RU 5211) [20], funded by the German Research Foundation (DFG). The overall aim of this interdisciplinary research unit is to identify generic and disease-specific risk factors and aetiological mechanisms of symptom persistence in a range of medical conditions, thereby providing a basis for evidence-based interventions for persistent somatic symptoms. Seven projects are investigating risk factors and mechanisms of symptom persistence in 10 different medical conditions [26‒31]. The persistent somatic symptoms being studied include fatigue, gastrointestinal symptoms, and pruritus in a variety of somatic, functional somatic, and mental health conditions. The study designs are prospective and share common assessment points, core instruments, and outcome variables to allow comparison and validation of results across projects and conditions [20]. The results of the SOMACROSS research unit are currently being analysed. It is anticipated that a more comprehensive knowledge of the mechanisms leading to persistent somatic symptoms will help to identify patients at risk at an earlier stage and to develop prevention and tailored treatment approaches for patients suffering from persistent somatic symptoms.Another example of transdiagnostic research can be found at the German Centre for Mental Health (DZPG). In this cross-sectional multicentre study, fatigue is being studied transdiagnostically in patients with malignant diseases, multiple sclerosis, chronic pain disorder, chronic kidney disease, diabetes mellitus, chronic inflammatory bowel disease, depression, and post-COVID-19 condition. The aim is to provide an in-depth phenotyping of different aspects of fatigue through a pseudonymized online survey, psychometric characterization using validated scales, and investigation of disease activity markers, disease progression, and blood parameters. This should also enable network analyses to investigate disease-specific and transdiagnostic fatigue symptom networks. Another aim of this study is to better define commonalities and differences in somatic symptom profiles and biopsychosocial risk factors, including post-exertional malaise, for which its status as a diagnostic marker and/or indicator of severity is currently under debate.It is not possible to conduct differentiated research into the causes of each individual persistent somatic symptom. Apart from that, the potential of a transdiagnostic and transsymptomatic approach to persistent somatic symptom research lies in the synergy processes in the research itself and in mutual learning. For example, if depression is consistently identified as a risk factor for persistent fatigue in conditions such as multiple sclerosis, post-stroke, heart failure, inflammatory bowel disease, and rheumatoid arthritis [9, 10, 12‒14], then it is very likely that depression is also a significant risk factor for persistent fatigue in chronic kidney or liver disease [26, 28].To substantiate the transdiagnostic relevance of specific risk factors, well-designed studies that examine the same risk factors and mechanisms across multiple diagnoses are needed [1]. Such studies, particularly those with large sample sizes and prospective designs, can examine a broad spectrum of risk factors, thereby elucidating both individual and cumulative contributions to the persistence of somatic symptoms. Ideally, the many overlapping potential risk factors examined can then be reduced to their core content. There are still far too few such transdiagnostic or transsymptomatic studies, and our aim must be to conduct more of them in the future. The ultimate goal is to identify a set of potentially modifiable risk factors for persistent somatic symptoms that could serve as preventive and therapeutic targets in future clinical intervention trials.It is likely that there are several modifiable variables that need to be addressed in such mechanism-based interventions for persistent somatic symptoms. In this case, these interventions might be multimodal. For example, interventions might combine medication treatment of the underlying medical condition, psychotherapeutic techniques targeting dysfunctional symptom expectations, and strategies to increase physical activity [1, 32]. In the case of severe and therapy-resistant persistent somatic symptoms, this may require complex and interdisciplinary interventions, such as those provided by the specialist field of psychosomatic medicine and psychotherapy in Germany in both inpatient and outpatient settings [33, 34]. In addition, the development of future measures for the prevention, information, and treatment of persistent somatic symptoms must increasingly involve patients, their families, and the general public.Adopting a transdiagnostic and transsymptomatic perspective on persistent somatic symptoms requires considerable effort and interdisciplinary collaboration. This approach can be time-consuming and may involve crossing institutional and disciplinary boundaries. There is also a need to rethink the training of physicians and other health professionals, as well as research funding, so that transdiagnostic and transsymptomatic approaches do not fall between the cracks of disciplines and responsibilities. Despite these challenges, the potential benefits are considerable. Recent publications provide promising evidence of the effectiveness of these approaches [35, 36]. If persistent somatic symptoms can be managed with transdiagnostic and transsymptomatic interventions that are effective, targeted, and mechanism-based, this is likely to lead to increased self-efficacy among clinicians and reduced burden and stigma for patients.B.L. reports research funding (no personal honoraria) from the German Research Foundation, the German Federal Ministry of Education and Research, the German Innovation Committee at the Joint Federal Committee, the European Commission’s Horizon 2020 Framework Programme, the European Joint Programme for Rare Diseases (EJP), the Ministry of Science, Research and Equality of the Free and Hanseatic City of Hamburg, Germany, and the Foundation Psychosomatics of Spinal Diseases, Stuttgart, Germany. He received remunerations for several scientific book articles from various book publishers, from the Norddeutscher Rundfunk (NDR) for interviews in medical knowledge programmes on public television, and as a committee member from Aarhus University, Denmark. He received travel expenses from the European Association of Psychosomatic Medicine (EAPM), and accommodation and meals from the Societatea de Medicina Biopsihosociala, Romania, for a presentation at the EAPM Academy at the Conferința Națională de Psihosomatică, Cluj-Napoca, Romania, October 2023. He received a travel grant for a lecture on the occasion of the presentation of the Alison Creed Award at the EAPM Conference in Lausanne, 12–15 June 2024. He received remuneration and travel expenses for lecture at the Lindauer Psychotherapiewochen, April 2024. He is President of the German College of Psychosomatic Medicine (DKPM) (unpaid) since March 2024 and was a member of the Board of the European Association of Psychosomatic Medicine (EAPM) (unpaid) until 2022. He is a member of the EIFFEL Study Oversight Committee (unpaid). S.Z. reports research funding (no personal honoraria) from the German Research Foundation and the German Federal Ministry of Education and Research and the German Cancer Aid (DKH). He has received remunerations for editorial work for Frontiers in Psychiatry and Thieme (PPmP, Psychup2date). He is the president of the International College of Psychosomatic Medicine (ICPM) (unpaid) from September 2024. O.V.B. is a holder of a Mercator Fellowship of the Deutsche Forschungsgemeinschaft. He received payment of travel expenses and remunerations for presentations at several universities and noncommercial scientific organizations. P.H. reports research funding (no personal honoraria) from the German Research Foundation and the German Federal Ministry of Education and Research. He has received remunerations for a book chapter from Oxford University Press and for a book from Springer Nature. He has received remunerations as a scientific programme consultant of the Lindauer Psychotherapietage and has received payment of travel expenses and remunerations for presentations at several universities and other public hospitals in Germany (no commercial companies). He has received travel expenses and registration fees for the German Congress of Psychosomatic Medicine. He has received remunerations as a committee member from Aarhus University, Denmark. He has been a board member of the EAPM (unpaid) since 2023.This work was carried out in parts within the framework of the Research Unit 5211 (FOR 5211) “Persistent SOMAtic Symptoms ACROSS Diseases: From Risk Factors to Modification (SOMACROSS),” funded by the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG; Grant Nos. GZ LO 766/21-1 and GZ LO 766/22-1).B.L. wrote the first draft of the editorial. S.Z., O.V.B., and P.H. have contributed to parts of the editorial. B.L., S.Z., O.V.B., and P.H. have critically reviewed it for important intellectual content, revised the editorial, and have approved the final version for publication. B.L., S.Z., O.V.B., and P.H. agree to take responsibility for all aspects of this editorial.

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