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PERSPECTIVE article

Front. Public Health, 04 November 2022
Sec. Public Mental Health
This article is part of the Research Topic Insights in Public Mental Health: 2022 View all 14 articles

Recent developments on psychological factors in medically unexplained symptoms and somatoform disorders

  • Faculty of Psychology, University of Vienna, Vienna, Austria

Somatic symptoms which are not fully explained by a medical condition (medically unexplained symptoms) have a high relevance for the public health. They are very common both in the general population and in patients in health care, and may develop into chronic impairing conditions such as somatoform disorders. In recent years, the relevance of specific negative psychological factors for the diagnosis and the stability of somatoform disorders and for the impairment by medically unexplained symptoms gained more and more attention. This resulted—among others- in core changes in the diagnostic classification criteria of somatoform disorders. Against this background, the present “Perspective” will outline recent developments and findings in the area of medically unexplained somatic symptoms and somatoform disorders. Moreover, it will lay a special focus on evidence on specific negative psychological factors that may influence the course of unexplained somatic symptoms and disorders and the impairment caused by these symptoms.

Introduction

Pain, gastrointestinal, cardiovascular, or other somatic symptoms which are not fully explained by a medical condition (medically unexplained symptoms), are very common both in the general population and in patients in health care (14). While most medically unexplained somatic symptoms are transient or do not cause impairment, in some cases they develop into chronic disabling complaints or full-blown somatoform disorders, which are associated with high health care utilization and severe impairment (58). In addition to the key role of impairing medically unexplained symptoms in somatoform disorders, there is evidence that persons with other mental disorders, such as depressive disorders, frequently suffer from medically unexplained symptoms and that medically unexplained symptoms may even negatively influence their course (915).

This “Perspective” will outline recent developments in the area of medically unexplained somatic symptoms and somatoform disorders from the perspective of the Author, with a special focus on psychological factors that may influence their course and the impairment caused by these symptoms.

Somatoform disorders in the DSM and the ICD

Somatoform disorders are among the most frequent mental disorders, with prevalence rates estimated to be 5–6% in the general population (16). They were introduced as a diagnostic entity in the third version of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III) (17) and were retained in the fourth version of the manual (DSM-IV) (18). In the DSM-IV, the prototype of somatoform disorders was somatization disorder, which was defined by at least eight medically unexplained somatic symptoms in four different organic systems persisting over several years and beginning before the age of 30 years. Similarly, the International Classification of Diseases, tenth version (ICD-10) (19), contained the diagnosis of somatization disorder, which was defined by at least six medically unexplained somatic symptoms in two different organic systems persisting over 2 years. However, prevalence rates for the somatization disorder were very low, i.e., ~0.4% in the general population and 0.5–6.0% in primary or secondary care (2022). Moreover, the conceptualization was criticized with regard to utility and validity, since, among other things, evidence showed that many persons with multiple medically unexplained symptoms did not fulfill the strict criteria for somatization disorder despite their high impairment (2325). In addition, somatization disorder was found to be associated with a strong recollection bias regarding symptoms (26). In general, the required dichotomization of bodily complaints into either “medically explained” or “medically unexplained” proved to be difficult even for specialists and brought about low interrater reliability {(2729); but see (30) for an opposing perspective}. Occasionally, a transition of considering a symptom to be medically explained or not has occurred over time in both directions (4, 27, 31). The process of diagnosing was further complicated by patients whose complaints are related to a medical disease, but whose impairment exceeded the “expected” extent (32). Therefore, it was proposed that the dualistic distinction between “unexplained” and “medically explained symptoms” should be abandoned (3336). This proposition was supported by a study in the general population, showing that most medically unexplained symptoms and medically explained symptoms resulted in comparable impairment and showed similar stability (37). The findings suggested that research should focus on the formulation and exploration of additional significant non-somatic classification criteria and factors that influence the impairment by medically unexplained symptoms, i.e., specifically on psychological factors. This should avoid shortcomings in diagnostic classification systems for somatoform disorders and consequently enable adequate management of impairing medically unexplained symptoms within the health care system. Taking into account the criticism outlined above, the DSM 5th edition (DSM-5) (38) and the ICD 11th edition (ICD-11) revised the former sections of somatoform disorders. In the DSM-5, some of the former somatoform disorders were replaced with the new diagnosis of somatic symptom disorder (300.82). For this diagnosis, the former differentiation between medically unexplained and explained somatic symptoms was abandoned, such that medically explained symptoms also counted for the core classification criterion of impairing symptoms. In addition, psychological classification criteria (criterion B) were included (see section 3 below). Similarly, the ICD-11 (39) introduced the new classification bodily distress disorder which is characterized by persistent and distressing somatic symptoms (including medically explained symptoms) which draw excessive attention.

Psychological factors in medically unexplained symptoms and somatoform disorders

Since persistent medically unexplained somatic symptoms and somatoform disorders bring about high costs for health care systems and are among the leading causes of disability (8), it is highly relevant to investigate psychological factors that characterize and influence these symptoms and disorders. The intensity of and impairment by medically unexplained symptoms, i.e., their interference with daily life, as well as health care utilization, are seen as core outcome criteria in the treatment of persons suffering from somatoform disorders (40). Therefore, the investigation of psychological factors that influence these criteria is of major importance in order to improve the diagnosis and treatment of affected persons. Furthermore, the investigation of mechanisms underlying the associations between medically unexplained symptoms and their perceived intensity and impairment is of high interest for the provision of appropriate and timely intervention strategies.

Evidence suggested that in addition to more unspecific factors such as early childhood trauma or insecure attachment (41), specific negative psychological factors such as catastrophizing, negative affectivity, rumination, avoidance, health anxiety, or a negative physical self-concept have a substantial influence on the transition from unproblematic medically unexplained somatic symptoms to severely impairing complaints and somatoform disorders. Individuals may differ in the extent to which negative psychological factors occur. Evidence suggested that persons with chronic and disabling medically unexplained symptoms and somatoform disorders show more negative psychological factors than do persons without such symptoms, and that negative psychological factors strongly influence the impairment and illness behavior of persons with chronic medically unexplained symptoms as well as the stability of these symptoms (4244). Individuals with more negative psychological factors may perceive medically unexplained symptoms as more threatening and may consequently show a higher cognitive, emotional, and behavioral awareness of these symptoms. For instance, a recent study in the general population by Toussaint et al. (45) found that persons who suffered from somatic symptoms and a high degree of psychological symptoms related to the somatic symptoms (i.e., persons who fulfilled the criteria for a somatic symptom disorder) reported to spend eight times more time a day dedicated to their somatic symptoms (4 h/day) in comparison to persons with less somatic symptoms and way lower psychological symptoms (half an hour/day). This process may, in turn, lead to increased negative bodily sensations, resulting in a higher intensity of and impairment by medically unexplained symptoms (43, 4649). Indeed, Toussaint et al. (45) found that the psychological symptoms were the strongest (cross-sectional statistical) predictor for the self-rated health status in their general population sample.

The topic of psychological factors also bears relevance with regard to the classification of impairing medically unexplained symptoms and somatoform disorders. To justify the classification of somatoform disorders as a DSM or ICD section F/mental disorders diagnosis (18, 19, 38), positive psychological classification criteria were required (25). A study in the general population evaluated specific negative psychological factors that could be used as classification criteria for impairing somatic/somatoform syndromes requiring health care {e.g. (42, 44)}. Specifically, it aimed to determine the relevance of these negative psychological factors with regard to impairment by (medically unexplained) somatic symptoms and health care utilization due to these symptoms. These criteria should help to identify those people who need health care, as compared to people who are able to cope with their symptoms themselves, without health care. Moreover, the criteria should identify those patients who are seriously impaired by the symptoms, in contrast to those who have some symptoms but do not feel impaired. The study authors found several negative psychological factors that might influence whether persons with somatic symptoms require health care and/or feel impaired by their symptoms: (1) ruminations about somatic complaints and worrying about health and illness; (2) catastrophizing of bodily sensations; (3) somatic illness attributions despite contradictory medical information; (4) a self-concept of bodily weakness; (5) low symptom tolerance and immediate need for medical help when symptoms occur; (6) avoidance of physical activity that could cause sweating or heart rate acceleration; (7) disuse of body parts because of complaints; (8) feelings of desperation because of symptoms and negative affectivity. Further, longitudinal analyses showed that persons fulfilling the negative psychological factors reassurance seeking, body checking, catastrophizing of physical sensations, avoidance of physical activities, a self-concept of bodily weakness„ and negative affectivity had a two to ten higher odds ratio for suffering from a somatoform disorder 1–4 years later, with up to 90% correct predictions for the overall model (42). Other studies used the comparison between different alternative classification proposals {e.g., bodily distress disorder introduced by Fink et al. (50), polysymptomatic disorder introduced by Rief et al. (51)} to determine the possible value of specific psychological classification criteria (51, 52). They found that the inclusion of psychological and behavioral criteria increased the concurrent validity of the proposals and partly also the predictive validity.

Based on the evidence outlined above, the DSM-5 (38) and the ICD-11 (39) revised their former sections of somatoform disorders, and included specific psychological criteria, i.e., health anxiety, catastrophizing, or high time or energy devoted to the preoccupation with somatic symptoms in the DSM-5, and excessive attention that can not be alleviated by clinical examinations and reassurance of innocuousness in the ICD-11. Nevertheless, the described findings suggested that, although the validity of the diagnoses was improved by the inclusion of psychological classification criteria {for a recent scoping review on evidence on somatic symptom disorder please see (41)}, there were some shortcomings with regard to the limited number of considered negative psychological factors. For instance, it would be advisable to widen somatic symptom disorder's psychological criterion (criterion B) through the inclusion of a self-concept of bodily weakness and negative affectivity, and also to specify the existing criteria with regard to rumination and avoidance (42, 44). Similarly, the bodily distress disorder may benefit from including a broader range of psychological criteria and/or further specification of “excessive attention” (i.e., with regard to behavioral, emotional, and cognitive indications). In this regard, the study of Toussaint et al. mentioned above (45) took an important first step in shedding light on the “excessiveness” in terms of daily time dedicated to somatic symptoms. Further refinement of the diagnostic criteria may help to even better meet the requirements regarding validity and consequently the needs of patients with mainly medically unexplained symptoms, their treating clinicians, and researchers.

Psychological factors in the daily lives of persons suffering from medically unexplained symptoms

Despite the dynamic trajectories and volatility of medically unexplained symptoms (4, 37, 5356), most studies investigating medically unexplained symptoms and negative psychological factors used rather static data, i.e., questionnaires or data from only one time point, or assessed persons in the laboratory, i.e., in a rather artificial setting far removed from their daily life. While these studies provided valuable insights into how to establish the differential relationships between medically unexplained symptoms, negative psychological factors, and impairment, they were unable to capture dynamic associations and mechanisms, and their results may not be generalizable to individuals' daily life. To elucidate the dynamic associations between negative psychological factors and the intensity of and impairment by medically unexplained symptoms, a micro-longitudinal design using ecological momentary assessment (EMA) may represent the best choice. An EMA approach has the potential to provide insight into the occurrence of negative psychological factors and specific reactions as they actually occur in everyday life (5761). Moreover, such an approach avoids the limitations of cross-sectional or longer-term longitudinal designs {such as the inability to test causal relationships, low temporal resolution, memory biases, and losses to follow-up assessments (55)}, and of experimental approaches (such as the lack of generalizability of observed relationships).

Only a handful of studies have investigated associations between single negative psychological factors or stress and impairment by somatic symptoms using ambulatory assessment designs (48, 53, 56, 6265). The respective findings suggest negative influences of negative psychological factors and stress on daily somatic symptoms in healthy students or persons suffering from functional somatic syndromes/medically unexplained symptoms. However, these studies were limited both in generalizability and ecological validity, as they mainly investigated small groups, focused on pain and single psychological factors, had very short assessment periods, or included a low number of assessments per day. Two studies investigated the relevance of several specific negative psychological factors in the daily life of women suffering from medically unexplained symptoms using an EMA design with several assessments per day over a period of 14 days (66, 67). They focused exclusively on women due to the female preponderance regarding somatoform disorders/somatic symptom disorder and depressive disorders (8, 68) and given the sex-specific differences in biological responses to stress (6971).

The first study investigated the everyday life occurrence of negative psychological factors in women suffering from chronic medically unexplained symptoms in the form of widespread pain (fibromyalgia syndrome) (66). In addition, the predictive value of negative psychological factors concerning the intensity of and impairment by the pain was investigated. In this study, ambulatory data were assessed over 14 consecutive days with six daily assessments via an iPod. Twenty-eight women suffering from chronic widespread pain estimated the strength of three negative psychological factors (somatic illness beliefs, health anxiety, time/energy devoted to pain or health concerns) and the intensity of momentary pain. The results showed that, on average, negative psychological factors occurred three to four times per day and had a mild to moderate severity. Interestingly, they were both concurrently and prospectively associated with momentary pain intensity and subjective impairment by pain. Negative psychological factors and pain medication explained 20% of the variance in pain intensity and 28% of the variance in subjective impairment.

The second study also included biological measures, as a major aspect of the negative consequences of negative psychological factors is their potential to elicit biological stress responses (67, 72, 73). These responses are coordinated by a complex system encompassing the hypothalamic-pituitary-adrenal (HPA) axis and the autonomic nervous system (7478), and may in turn also influence the intensity of and impairment by medically unexplained symptoms (65). Previous studies showed that the activity of these systems was differentially affected in persons with somatic symptom disorder and persons with depressive disorders. While the activity of the HPA axis is assumed to be reduced in individuals with impairing medically unexplained symptoms (7981), HPA axis hyperactivity is apparent in persons with depressive disorders (82, 83). A recent meta-analysis even found that the higher the cortisol levels in persons with depressive disorders at the start of psychological therapy, the worse the outcome at the end of treatment (84). In the EMA study, 29 women with somatic symptom disorder (based on medically unexplained somatic symptoms) and 29 women with depressive disorders participated. In this study, intensity of and impairment by somatic symptoms, negative psychological factors, and stress biomarkers (cortisol and alpha-amylase) were assessed five times per day over 14 consecutive days using an electronic device and saliva samples. The results showed that the more negative psychological factors were present, the higher were the concurrent and time-lagged intensity of and impairment by somatic symptoms in women with somatic symptom disorder and with depressive disorders. In women with depressive disorders, negative psychological factors were associated with higher levels of salivary cortisol. In contrast, they were associated with lower levels in women with somatic symptom disorder. In women with somatic symptom disorder, lower cortisol levels were associated with higher intensity at the next measurement time point, i.e., 3–4 h later, emphasizing the utility of stress-reducing interventions in this group (67).

The two EMA studies impressively demonstrated the strong immediate and delayed impact of specific negative psychological factors on the intensity of and impairment by somatic symptoms in the daily life of affected persons with different disorders. Thus, negative psychological factors may be considered as transdiagnostic factors in the development and treatment of impairing (medically unexplained) somatic symptoms. With the unique combination of subjective and biological measures the second study found support for the possible mediating role of the HPA axis in the association between negative psychological factors and the suffering from somatic symptoms. These results are highly relevant, as they can inform the development of new treatment strategies which use ecological momentary intervention approaches focusing on negative psychological factors in persons suffering from impairing somatic symptoms (85). Since the two EMA studies only included women without any medical condition that may affect endocrine or autonomic functioning (because of the investigated biological markers), the generalizability of the findings to persons with such a medical condition remains unclear. Since studies showed that specific negative psychological factors may aggravate somatic complaints accompanying medical illnesses to an extent that cannot be fully explained by the underlying illness (8689), the findings of the EMA studies may bear some relevance for persons suffering from a medical condition. However, the inclusion of medical conditions may have changed the characteristics of the investigated group and the strength of the presented psychological factors, since a study suggested that the diagnosis of somatic symptom disorder becomes less strict when medically explained somatic symptoms are included (90). With the lack of clear criteria for the fulfillment of the B criteria for somatic symptom disorder in the presence of medical conditions, the diagnosis may become less reliable and may lose validity. Future studies should shed light on this important issue.

Discussion

The presented evidence showed the relevance of specific negative psychological factors for the conceptualization, the diagnosis, and the treatment of medically (un)explained symptoms and various diagnostic entities in which these symptoms are pathognomonic, and showed recent developments in this regard.

The findings underlined the importance to consider negative psychological factors in the context of medically unexplained symptoms, as these factors may have the potential to explain why medically unexplained somatic symptoms cause so much impairment without a (known) underlying medical disease. Indeed, the evidence outlined confirmed the high relevance of specific negative psychological factors for the concurrent and predictive intensity of and impairment by medically unexplained symptoms in the general population. It showed that specific negative psychological factors contributed to the maintenance of multiple impairing medically unexplained symptoms over several years, as well as to the direct impairment by somatic symptoms in the daily lives of affected persons. A recent EMA study even suggested that these specific negative psychological factors were transdiagnostic, since they were equally relevant for the impairment by somatic symptoms in women with depressive disorders as they were in women with somatic symptom disorder.

Moreover, the presented findings suggest that for persons suffering from medially unexplained somatic symptoms, the current classification criteria for somatic symptom disorder and bodily distress disorder might be further improved by including additional psychological classification criteria (e.g., reassurance seeking, body checking, a self-concept of bodily weakness, avoidance behavior, and negative affectivity) or by the use of these criteria/factors to specify the current psychological criteria. This could improve the early detection and timely treatment of persons at risk for a chronic course of somatoform disorders/somatic symptom disorder/bodily distress disorder. However, it is important to note that while the suggestions for additional psychological classification criteria is based on a broad evidence [see above and (41)], there is no consensus on the exact set of psychological criteria that may be relevant for a diagnosis in the field of somatoform disorders. Moreover, the relevance of specific criteria may vary between cultures [e.g., (90, 91)].

Despite the intriguing relevance of psychological classification criteria, there may also be cases where psychological classification criteria should not be mandatory for a diagnosis. As Burton et al. (92) suggest in their proposition of the category functional somatic disorders, there may be need for a diagnosis that captures persons suffering from persistent impairing functional somatic symptoms or syndromes (e.g., fibromyalgia or irritable bowel syndrome), who may or may not fulfill additional psychological criteria {for a recent review on functional somatic syndromes also see (93)}.

The findings of the studies using an EMA design provided further scientific groundwork for treatments of persons suffering from chronic medically unexplained symptoms. They supported the rationale of treatment approaches focusing on cognitive-behavioral factors in general (94), as well as approaches considering negative affectivity and emotion regulation (95, 96) and avoidance (97) in particular. Furthermore, they can inform the development of new treatment strategies which use ecological momentary intervention approaches to reduce negative psychological factors in persons suffering from impairing somatic symptoms (85). Future studies should follow this promising avenue.

Data availability statement

The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.

Author contributions

The author confirms being the sole contributor of this work and has approved it for publication.

Conflict of interest

The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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References

1. Leiknes KA, Finset A, Moum T, Sandanger I. Course and predictors of medically unexplained pain symptoms in the general population. J Psychosom Res. (2007) 62:119–28. doi: 10.1016/j.jpsychores.2006.08.009

PubMed Abstract | CrossRef Full Text | Google Scholar

2. Kurita GP, Sjogren P, Juel K, Hojsted J, Ekholm O. The burden of chronic pain: a cross-sectional survey focussing on diseases, immigration, and opioid use. Pain. (2012) 153:2332–8. doi: 10.1016/j.pain.2012.07.023

PubMed Abstract | CrossRef Full Text | Google Scholar

3. Steinbrecher N, Koerber S, Frieser D, Hiller W. The prevalence of medically unexplained symptoms in primary care. Psychosomatics. (2011) 52:263–71. doi: 10.1016/j.psym.2011.01.007

PubMed Abstract | CrossRef Full Text | Google Scholar

4. Claassen-van Dessel N, van der Wouden JC, Hoekstra T, Dekker J, van der Horst HE. The 2-year course of medically unexplained physical symptoms (MUPS) in terms of symptom severity and functional status: results of the PROSPECTS cohort study. J Psychosom Res. (2018) 104:76–87. doi: 10.1016/j.jpsychores.2017.11.012

PubMed Abstract | CrossRef Full Text | Google Scholar

5. Mewes R, Rief W, Glaesmer H, Martin A, Brähler E. Lower decision threshold for doctor visits as a predictor of health care use in somatoform disorders and the general population. Psychosom Med. (2008) 70:A66. doi: 10.1016/j.genhosppsych.2008.04.007

PubMed Abstract | CrossRef Full Text | Google Scholar

6. Mewes R, Rief W, Stenzel N, Glaesmer H, Martin A, Brahler E. What is “normal” disability? An investigation of disability in the general population. Pain. (2009) 142:36–41. doi: 10.1016/j.pain.2008.11.007

PubMed Abstract | CrossRef Full Text | Google Scholar

7. van der Sluijs JFV, ten Have M, de Graaf R, Rijnders CAT, van Marwijk HWJ, van der Feltz-Cornelis CM. Predictors of persistent medically unexplained physical symptoms: findings from a general population study. Front Psychiatry. (2018) 9:613. doi: 10.3389/fpsyt.2018.00613

PubMed Abstract | CrossRef Full Text | Google Scholar

8. GBD 2016 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the global burden of disease study 2016. Lancet. (2017) 390:1211–59. doi: 10.1016/S0140-6736(17)32154-2

PubMed Abstract | CrossRef Full Text | Google Scholar

9. Hung CI, Liu CY, Yang CH. Persistent depressive disorder has long-term negative impacts on depression, anxiety, and somatic symptoms at 10-year follow-up among patients with major depressive disorder. J Affect Disord. (2019) 243:255–61. doi: 10.1016/j.jad.2018.09.068

PubMed Abstract | CrossRef Full Text | Google Scholar

10. Huijbregts KM, van der Feltz-Cornelis CM, van Marwijk HW, de Jong FJ, van der Windt DA, Beekman AT. Negative association of concomitant physical symptoms with the course of major depressive disorder: a systematic review. J Psychosom Res. (2010) 68:511–9. doi: 10.1016/j.jpsychores.2009.11.009

PubMed Abstract | CrossRef Full Text | Google Scholar

11. Simon GE, VonKorff M, Piccinelli M, Fullerton C, Ormel J. An international study of the relation between somatic symptoms and depression. N Engl J Med. (1999) 341:1329–35. doi: 10.1056/NEJM199910283411801

PubMed Abstract | CrossRef Full Text | Google Scholar

12. Mergl R, Seidscheck I, Allgaier AK, Moller HJ, Hegerl U, Henkel V. Depressive, anxiety, and somatoform disorders in primary care: prevalence and recognition. Depress Anxiety. (2007) 24:185–95. doi: 10.1002/da.20192

PubMed Abstract | CrossRef Full Text | Google Scholar

13. Barsky AJ, Orav EJ, Bates DW. Somatization increases medical utilization and costs independent of psychiatric and medical comorbidity. Arch Gen Psychiatry. (2005) 62:903–10. doi: 10.1001/archpsyc.62.8.903

PubMed Abstract | CrossRef Full Text | Google Scholar

14. Harris AM, Orav EJ, Bates DW, Barsky AJ. Somatization increases disability independent of comorbidity. J Gen Intern Med. (2009) 24:155–61. doi: 10.1007/s11606-008-0845-0

PubMed Abstract | CrossRef Full Text | Google Scholar

15. Löwe B, Spitzer RL, Williams JB, Mussell M, Schellberg D, Kroenke K. Depression, anxiety and somatization in primary care: syndrome overlap and functional impairment. Gen Hosp Psychiatry. (2008) 30:191–9. doi: 10.1016/j.genhosppsych.2008.01.001

PubMed Abstract | CrossRef Full Text | Google Scholar

16. Wittchen HU, Jacobi F, Rehm J, Gustavsson A, Svensson M, Jonsson B, et al. The size and burden of mental disorders and other disorders of the brain in Europe 2010. Eur Neuropsychopharmacol. (2011) 21:655–79. doi: 10.1016/j.euroneuro.2011.07.018

PubMed Abstract | CrossRef Full Text | Google Scholar

17. Hiller W, Rief W. Why DSM-III was right to introduce the concept of somatoform disorders. Psychosomatics. (2005) 46:105–8. doi: 10.1176/appi.psy.46.2.105

PubMed Abstract | CrossRef Full Text | Google Scholar

18. APA. Diagnostic and Statistical Manual of Mental Disorders (fourth edition) (DSM-IV). Washington, DC: American Psychiatric Association (1994).

19. WHO. International Classifications of Diseases 10th Revision. World Health Organization (2007).

20. Creed F, Barsky A. A systematic review of the epidemiology of somatisation disorder and hypochondriasis. J Psychosom Res. (2004) 56:391–408. doi: 10.1016/S0022-3999(03)00622-6

PubMed Abstract | CrossRef Full Text | Google Scholar

21. de Waal MW, Arnold IA, Eekhof JA, van Hemert AM. Somatoform disorders in general practice: prevalence, functional impairment and comorbidity with anxiety and depressive disorders. Br J Psychiatry. (2004) 184:470–6. doi: 10.1192/bjp.184.6.470

PubMed Abstract | CrossRef Full Text | Google Scholar

22. Fink P, Hansen MS, Oxhoj ML. The prevalence of somatoform disorders among internal medical inpatients. J Psychosom Res. (2004) 56:413–8. doi: 10.1016/S0022-3999(03)00624-X

PubMed Abstract | CrossRef Full Text | Google Scholar

23. Mayou R, Kirmayer LJ, Simon G, Kroenke K, Sharpe M. Somatoform disorders: time for a new approach in DSM-V. Am J Psychiatry. (2005) 162:847–55. doi: 10.1176/appi.ajp.162.5.847

PubMed Abstract | CrossRef Full Text | Google Scholar

24. Rief W, Isaac M. Are somatoform disorders 'mental disorders'? A contribution to the current debate. Curr Opin Psychiatry. (2007) 20:143–6. doi: 10.1097/YCO.0b013e3280346999

PubMed Abstract | CrossRef Full Text | Google Scholar

25. Gureje O, Reed GM. Bodily distress disorder in ICD-11: problems and prospects. World Psychiatry. (2016) 15:291–2. doi: 10.1002/wps.20353

PubMed Abstract | CrossRef Full Text | Google Scholar

26. Rief W, Rojas G. Stability of somatoform symptoms—implications for classification. Psychosom Med. (2007) 69:864–9. doi: 10.1097/PSY.0b013e31815b006e

PubMed Abstract | CrossRef Full Text | Google Scholar

27. Leiknes KA, Finset A, Moum T, Sandanger I. Methodological issues concerning lifetime medically unexplained and medically explained symptoms of the composite international diagnostic interview: a prospective 11-year follow-up study. J Psychosom Res. (2006) 61:169–79. doi: 10.1016/j.jpsychores.2006.01.007

PubMed Abstract | CrossRef Full Text | Google Scholar

28. McFarlane AC, Ellis N, Barton C, Browne D, Van Hooff M. The conundrum of medically unexplained symptoms: questions to consider. Psychosomatics. (2008) 49:369–77. doi: 10.1176/appi.psy.49.5.369

PubMed Abstract | CrossRef Full Text | Google Scholar

29. Sharpe M, Mayou R, Walker J. Bodily symptoms: new approaches to classification. J Psychosom Res. (2006) 60:353–6. doi: 10.1016/j.jpsychores.2006.01.020

PubMed Abstract | CrossRef Full Text | Google Scholar

30. Scamvougeras A, Howard A. Somatic symptom disorder, medically unexplained symptoms, somatoform disorders, functional neurological disorder: how DSM-5 got it wrong. Can J Psychiatry. (2020) 2020:706743720912858. doi: 10.1177/0706743720912858

PubMed Abstract | CrossRef Full Text | Google Scholar

31. Koch H, van Bokhoven MA, Bindels PJ, van der Weijden T, Dinant GJ. ter Riet G. The course of newly presented unexplained complaints in general practice patients: a prospective cohort study. Fam Pract. (2009) 26:455–65. doi: 10.1093/fampra/cmp067

PubMed Abstract | CrossRef Full Text | Google Scholar

32. Brown RJ. Introduction to the special issue on medically unexplained symptoms: background and future directions. Clin Psychol Rev. (2007) 27:769–80. doi: 10.1016/j.cpr.2007.07.003

PubMed Abstract | CrossRef Full Text | Google Scholar

33. Creed F. Medically unexplained symptoms - blurring the line between “mental” and “physical” in somatoform disorders. J Psychosom Res. (2009) 67:185–7. doi: 10.1016/j.jpsychores.2009.07.001

PubMed Abstract | CrossRef Full Text | Google Scholar

34. Dimsdale J, Creed F. The proposed diagnosis of somatic symptom disorders in DSM-V to replace somatoform disorders in DSM-IV - a preliminary report. J Psychosom Res. (2009) 66:473–6. doi: 10.1016/j.jpsychores.2009.03.005

PubMed Abstract | CrossRef Full Text | Google Scholar

35. Löwe B, Mundt C, Herzog W, Brunner R, Backenstrass M, Kronmüller K, et al. Validity of current somatoform disorder diagnoses: perspectives for classification in DSM-V and ICD-11. Psychopathology. (2008) 41:4–9. doi: 10.1159/000109949

PubMed Abstract | CrossRef Full Text | Google Scholar

36. Creed FH, Davies I, Jackson J, Littlewood A, Chew-Graham C, Tomenson B, et al. The epidemiology of multiple somatic symptoms. J Psychosom Res. (2012) 72:311–7. doi: 10.1016/j.jpsychores.2012.01.009

PubMed Abstract | CrossRef Full Text | Google Scholar

37. Klaus K, Rief W, Brahler E, Martin A, Glaesmer H, Mewes R. The distinction between “medically unexplained” and “medically explained” in the context of somatoform disorders. Int J Behav Med. (2013) 20:161–71. doi: 10.1007/s12529-012-9245-2

PubMed Abstract | CrossRef Full Text | Google Scholar

38. Association AP. Diagnostic and Statistical Manual of Mental Disorders 4th Ed. (DSM-5). Arlington, VA: American Psychiatric Publishing (2013).

Google Scholar

39. WHO. International Classification of Diseases 11th Revision. World Health Organization (2022).

Google Scholar

40. Rief W, Burton C, Frostholm L, Henningsen P, Kleinstäuber M, Kop WJ, et al. Core outcome domains for clinical trials on somatic symptom disorder, bodily distress disorder, and functional somatic syndromes: European network on somatic symptom disorders recommendations. Psychosom Med. (2017) 79:1008–15. doi: 10.1097/PSY.0000000000000502

PubMed Abstract | CrossRef Full Text | Google Scholar

41. Löwe B, Levenson J, Depping M, Husing P, Kohlmann S, Lehmann M, et al. Somatic symptom disorder: a scoping review on the empirical evidence of a new diagnosis. Psychol Med. (2021) 2021:1–17. doi: 10.1016/j.jpsychores.2022.110876

PubMed Abstract | CrossRef Full Text | Google Scholar

42. Klaus K, Rief W, Brähler E, Martin A, Glaesmer H, Mewes R. Validating psychological classification criteria in the context of somatoform disorders: a one- and four-year follow-up. J Abnorm Psychol. (2015) 124:1092–101. doi: 10.1037/abn0000085

PubMed Abstract | CrossRef Full Text | Google Scholar

43. Martin A, Rief W. Relevance of cognitive and behavioral factors in medically unexplained syndromes and somatoform disorders. Psychiatric Clin North Am. (2011) 34:565–78. doi: 10.1016/j.psc.2011.05.007

PubMed Abstract | CrossRef Full Text | Google Scholar

44. Rief W, Mewes R, Martin A, Glaesmer H, Braehler E. Are psychological features useful in classifying patients with somatic symptoms? Psychosom Med. (2010) 72:648–55. doi: 10.1097/PSY.0b013e3181d73fce

PubMed Abstract | CrossRef Full Text | Google Scholar

45. Toussaint A, Husing P, Kohlmann S, Brähler E, Löwe B. Excessiveness in symptom-related thoughts, feelings, and behaviors: an investigation of somatic symptom disorders in the general population. Psychosom Med. (2021) 83:164–70. doi: 10.1097/PSY.0000000000000903

PubMed Abstract | CrossRef Full Text | Google Scholar

46. Köteles F, Witthöft M. Somatosensory amplification - an old construct from a new perspective. J Psychosom Res. (2017) 101:1–9. doi: 10.1016/j.jpsychores.2017.07.011

PubMed Abstract | CrossRef Full Text | Google Scholar

47. Perez DL, Barsky AJ, Vago DR, Baslet G, Silbersweig DA. A neural circuit framework for somatosensory amplification in somatoform disorders. J Neuropsychiatry Clin Neurosci. (2015) 27:e40–50. doi: 10.1176/appi.neuropsych.13070170

PubMed Abstract | CrossRef Full Text | Google Scholar

48. Spink GL, Jorgensen RS, Cristiano S. Cognitive and affective factors predicting daily somatic complaints in college students. J Couns Psychol. (2018) 65:110–9. doi: 10.1037/cou0000229

PubMed Abstract | CrossRef Full Text | Google Scholar

49. Barends H, Claassen-van Dessel N, van der Wouden JC, Twisk JWR, Terluin B, van der Horst HE, et al. Impact of symptom focusing and somatosensory amplification on persistent physical symptoms: a three-year follow-up study. J Psychosom Res. (2020) 135:110131. doi: 10.1016/j.jpsychores.2020.110131

PubMed Abstract | CrossRef Full Text | Google Scholar

50. Fink P, Schroder A. One single diagnosis, bodily distress syndrome, succeeded to capture 10 diagnostic categories of functional somatic syndromes and somatoform disorders. J Psychosom Res. (2010) 68:415–26. doi: 10.1016/j.jpsychores.2010.02.004

PubMed Abstract | CrossRef Full Text | Google Scholar

51. Rief W, Mewes R, Martin A, Glaesmer H, Brähler E. Evaluating new proposals for the psychiatric classification of patients with multiple somatic symptoms. Psychosom Med. (2011) 73:760–8. doi: 10.1097/PSY.0b013e318234eff6

PubMed Abstract | CrossRef Full Text | Google Scholar

52. Schumacher S, Rief W, Klaus K, Brähler E, Mewes R. Medium- and long-term prognostic validity of competing classification proposals for the former somatoform disorders. Psychol Med. (2017) 2017:1–14. doi: 10.1017/S0033291717000149

PubMed Abstract | CrossRef Full Text | Google Scholar

53. van Gils A, Burton C, Bos EH, Janssens KA, Schoevers RA, Rosmalen JG. Individual variation in temporal relationships between stress and functional somatic symptoms. J Psychosom Res. (2014) 77:34–9. doi: 10.1016/j.jpsychores.2014.04.006

PubMed Abstract | CrossRef Full Text | Google Scholar

54. de Hartman TC, Borghuis MS, Lucassen PL, van de Laar FA, Speckens AE, van Weel C. Medically unexplained symptoms, somatisation disorder and hypochondriasis: course and prognosis a systematic review. J Psychosom Res. (2009) 66:363–77. doi: 10.1016/j.jpsychores.2008.09.018

PubMed Abstract | CrossRef Full Text | Google Scholar

55. Van den Bergh O, Walentynowicz M. Accuracy and bias in retrospective symptom reporting. Curr Opin Psychiatry. (2016) 29:302–8. doi: 10.1097/YCO.0000000000000267

PubMed Abstract | CrossRef Full Text | Google Scholar

56. Houtveen JH, Lipovsky MM, Kool M, Sorbi M, Buhring MEF, van Broeckhuysen-Kloth S. The day-to-day concurrence of bodily complaints and affect in patients with severe somatoform disorder. Scand J Psychol. (2015) 56:553–9. doi: 10.1111/sjop.12228

PubMed Abstract | CrossRef Full Text | Google Scholar

57. Trull TJ, Ebner-Priemer U. Ambulatory assessment. Annu Rev Clin Psychol. (2013) 9:151–76. doi: 10.1146/annurev-clinpsy-050212-185510

PubMed Abstract | CrossRef Full Text | Google Scholar

58. Kim J, Kikuchi H, Yamamoto Y. Systematic comparison between ecological momentary assessment and day reconstruction method for fatigue and mood states in healthy adults. Br J Health Psychol. (2013) 18:155–67. doi: 10.1111/bjhp.12000

PubMed Abstract | CrossRef Full Text | Google Scholar

59. aan het Rot M, Hogenelst K, Schoevers RA. Mood disorders in everyday life: a systematic review of experience sampling and ecological momentary assessment studies. Clin Psychol Rev. (2012) 32:510–23. doi: 10.1016/j.cpr.2012.05.007

PubMed Abstract | CrossRef Full Text | Google Scholar

60. Myin-Germeys I, Kasanova Z, Vaessen T, Vachon H, Kirtley O, Viechtbauer W, et al. Experience sampling methodology in mental health research: new insights and technical developments. World Psychiatry. (2018) 17:123–32. doi: 10.1002/wps.20513

PubMed Abstract | CrossRef Full Text | Google Scholar

61. Ebner-Priemer UW, Trull TJ. Ambulatory assessment - an innovative and promising approach for clinical psychology. Eur Psychol. (2009) 14:109–19. doi: 10.1027/1016-9040.14.2.109

CrossRef Full Text | Google Scholar

62. Burton C, Weller D, Sharpe M. Functional somatic symptoms and psychological states: an electronic diary study. Psychosom Med. (2009) 71:77–83. doi: 10.1097/PSY.0b013e31818f2acb

PubMed Abstract | CrossRef Full Text | Google Scholar

63. Okifuji A, Bradshaw DH, Donaldson GW, Turk DC. Sequential analyses of daily symptoms in women with fibromyalgia syndrome. J Pain. (2011) 12:84–93. doi: 10.1016/j.jpain.2010.05.003

PubMed Abstract | CrossRef Full Text | Google Scholar

64. Bruehl S, Liu X, Burns JW, Chont M, Jamison RN. Associations between daily chronic pain intensity, daily anger expression, and trait anger expressiveness: an ecological momentary assessment study. Pain. (2012) 153:2352–8. doi: 10.1016/j.pain.2012.08.001

PubMed Abstract | CrossRef Full Text | Google Scholar

65. Fischer S, Doerr JM, Strahler J, Mewes R, Thieme K, Nater UM. Stress exacerbates pain in the everyday lives of women with fibromyalgia syndrome–the role of cortisol and alpha-amylase. Psychoneuroendocrinology. (2016) 63:68–77. doi: 10.1016/j.psyneuen.2015.09.018

PubMed Abstract | CrossRef Full Text | Google Scholar

66. Klaus K, Fischer S, Doerr JM, Nater UM. Mewes R. Classifying fibromyalgia syndrome as a mental disorder?-an ambulatory assessment study international. J Behav Med. (2017) 24:230–8. doi: 10.1007/s12529-016-9603-6

PubMed Abstract | CrossRef Full Text | Google Scholar

67. Mewes R, Feneberg AC, Doerr JM, Nater UM. Psychobiological mechanisms in somatic symptom disorder and depressive disorders: an ecological momentary assessment approach. Psychosom Med. (2022) 84:86–96. doi: 10.1097/PSY.0000000000001006

PubMed Abstract | CrossRef Full Text | Google Scholar

68. Brugha TS, Matthews R, Alonso J, Vilagut G, Fouweather T, Bruffaerts R, et al. Gender differences in mental health expectancies in early- and midlife in six European countries. Br J Psychiatry. (2013) 202:294–300. doi: 10.1192/bjp.bp.111.107003

PubMed Abstract | CrossRef Full Text | Google Scholar

69. Kudielka BM, Kirschbaum C. Sex differences in HPA axis responses to stress: a review. Biol Psychol. (2005) 69:113–32. doi: 10.1016/j.biopsycho.2004.11.009

PubMed Abstract | CrossRef Full Text | Google Scholar

70. Strahler J, Nater UM. Social stress: Sex-related differences in biological stress responses. Adv Med Biol. (2017) 104:119–30.

PubMed Abstract

71. Zorn JV, Schur RR, Boks MP, Kahn RS, Joels M, Vinkers CH. Cortisol stress reactivity across psychiatric disorders: a systematic review and meta-analysis. Psychoneuroendocrinology. (2017) 77:25–36. doi: 10.1016/j.psyneuen.2016.11.036

PubMed Abstract | CrossRef Full Text | Google Scholar

72. Jacobs N, Myin-Germeys I, Derom C, Delespaul P, van Os J, Nicolson NA, et al. momentary assessment study of the relationship between affective and adrenocortical stress responses in daily life. Biol Psychol. (2007) 74:60–6. doi: 10.1016/j.biopsycho.2006.07.002

PubMed Abstract | CrossRef Full Text | Google Scholar

73. Henningsen P, Gündel H, Kop WJ, Löwe B, Martin A, Rief W, et al. Persistent physical symptoms as perceptual dysregulation: a neuropsychobehavioral model and its clinical implications. Psychosom Med. (2018) 80:422–31. doi: 10.1097/PSY.0000000000000588

PubMed Abstract | CrossRef Full Text | Google Scholar

74. Stratakis CA, Chrousos GP. Neuroendocrinology and pathophysiology of the stress system. Ann N Y Acad Sci. (1995) 771:1–18. doi: 10.1111/j.1749-6632.1995.tb44666.x

PubMed Abstract | CrossRef Full Text | Google Scholar

75. Campeau S, Day HE, Helmreich DL, Kollack-Walker S, Watson SJ. Principles of psychoneuroendocrinology. Psychiatr Clin North Am. (1998) 21:259–76. doi: 10.1016/S0193-953X(05)70004-6

PubMed Abstract | CrossRef Full Text | Google Scholar

76. Huether G. The central adaptation syndrome: psychosocial stress as a trigger for adaptive modifications of brain structure and brain function. Prog Neurobiol. (1996) 48:569–612. doi: 10.1016/0301-0082(96)00003-2

PubMed Abstract | CrossRef Full Text | Google Scholar

77. Pacak K, Palkovits M. Stressor specificity of central neuroendocrine responses: implications for stress-related disorders. Endocr Rev. (2001) 22:502–48. doi: 10.1210/er.22.4.502

PubMed Abstract | CrossRef Full Text | Google Scholar

78. Ehlert U, Straub R. Physiological and emotional response to psychological stressors in psychiatric and psychosomatic disorders. Ann N Y Acad Sci. (1998) 851:477–86. doi: 10.1111/j.1749-6632.1998.tb09026.x

PubMed Abstract | CrossRef Full Text | Google Scholar

79. Rief W, Hennings A, Riemer S, Euteneuer F. Psychobiological differences between depression and somatization. J Psychosom Res. (2010) 68:495–502. doi: 10.1016/j.jpsychores.2010.02.001

PubMed Abstract | CrossRef Full Text | Google Scholar

80. Heim CM, Nater UM. Hypocortisolism and stress. Encyclopedia Stress. (2007) 2:400–7. doi: 10.1016/B978-012373947-6/00698-X

CrossRef Full Text | Google Scholar

81. Fischer S, Skoluda N, Ali N, Nater UM, Mewes R. Hair cortisol levels in women with medically unexplained symptoms. J Psychiatr Res. (2022) 146:77–82. doi: 10.1016/j.jpsychires.2021.12.044

PubMed Abstract | CrossRef Full Text | Google Scholar

82. Stetler C, Miller GE. Depression and hypothalamic-pituitary-adrenal activation: a quantitative summary of four decades of research. Psychosom Med. (2011) 73:114–26. doi: 10.1097/PSY.0b013e31820ad12b

PubMed Abstract | CrossRef Full Text | Google Scholar

83. Adam EK, Quinn ME, Tavernier R, McQuillan MT, Dahlke KA, Gilbert KE. Diurnal cortisol slopes and mental and physical health outcomes: a systematic review and meta-analysis. Psychoneuroendocrinology. (2017) 83:25–41. doi: 10.1016/j.psyneuen.2017.05.018

PubMed Abstract | CrossRef Full Text | Google Scholar

84. Fischer S, Strawbridge R, Vives AH, Cleare AJ. Cortisol as a predictor of psychological therapy response in depressive disorders: systematic review and meta-analysis. Br J Psychiatry. (2017) 210:105–9. doi: 10.1192/bjp.bp.115.180653

PubMed Abstract | CrossRef Full Text | Google Scholar

85. Myin-Germeys I, Klippel A, Steinhart H, Reininghaus U. Ecological momentary interventions in psychiatry. Curr Opin Psychiatry. (2016) 29:258–63. doi: 10.1097/YCO.0000000000000255

PubMed Abstract | CrossRef Full Text | Google Scholar

86. Edwards RR, Cahalan C, Mensing G, Smith M, Haythornthwaite JA. Pain, catastrophizing, and depression in the rheumatic diseases. Nat Rev Rheumatol. (2011) 7:216–24. doi: 10.1038/nrrheum.2011.2

PubMed Abstract | CrossRef Full Text | Google Scholar

87. McWilliams DF, Walsh DA. Pain mechanisms in rheumatoid arthritis. Clin Exp Rheumatol. (2017) 35(Suppl. 107):94–101.

Google Scholar

88. van der Wouden JC, Twisk JWR, Dekker J, van der Horst HE. Predicting the course of persistent physical symptoms: Development and internal validation of prediction models for symptom severity and functional status during 2 years of follow-up. J Psychosomatic Res. (2018) 108:1–13. doi: 10.1016/j.jpsychores.2018.02.009

PubMed Abstract | CrossRef Full Text | Google Scholar

89. Sullivan N, Phillips LA, Pigeon WR, Quigley KS, Graff F, Litke DR, et al. Coping with medically unexplained physical symptoms: the role of illness beliefs and behaviors. Int J Behav Med. (2019) 26:665–72. doi: 10.1007/s12529-019-09817-z

PubMed Abstract | CrossRef Full Text | Google Scholar

90. Huang WL, Chen IM, Chang FC, Liao SC. Somatic symptom disorder and undifferentiated somatoform disorder, which is broader? Response to “clinical value of DSM IV and DSM 5 criteria for diagnosing the most prevalent somatoform disorders in patients with medically unexplained physical symptoms (MUPS)”. J Psychosom Res. (2016) 89:114–5. doi: 10.1016/j.jpsychores.2016.07.014

PubMed Abstract | CrossRef Full Text | Google Scholar

91. Giesebrecht J, Grupp F, Reich H, Weise C, Mewes R. Relations between criteria for somatic symptom disorder and quality of life in asylum seekers living in Germany. J Psychosom Res. (2022) 160:110977. doi: 10.1016/j.jpsychores.2022.110977

PubMed Abstract | CrossRef Full Text | Google Scholar

92. Burton C, Fink P, Henningsen P, Löwe B, Rief W, Group E-S. Functional somatic disorders: discussion paper for a new common classification for research and clinical use. BMC Med. (2020) 18:34. doi: 10.1186/s12916-020-1505-4

PubMed Abstract | CrossRef Full Text | Google Scholar

93. Henningsen P, Zipfel S, Sattel H, Creed F. Management of functional somatic syndromes and bodily distress. Psychother Psychosom. (2018) 87:12–31. doi: 10.1159/000484413

PubMed Abstract | CrossRef Full Text | Google Scholar

94. Van Dessel N, Den Boeft M, van der Wouden JC, Kleinstäuber M, Leone SS, Terluin B, et al. Non-pharmacological interventions for somatoform disorders and medically unexplained physical symptoms (MUPS) in adults. Cochrane Database Syst Rev. (2014) 11:CD011142. doi: 10.1002/14651858.CD011142

PubMed Abstract | CrossRef Full Text | Google Scholar

95. Kleinstäuber M, Allwang C, Bailer J, Berking M, Brunahl C, Erkic M, et al. Cognitive behaviour therapy complemented with emotion regulation training for patients with persistent physical symptoms: a randomised clinical trial. Psychother Psychosom. (2019) 88:287–99. doi: 10.1159/000501621

PubMed Abstract | CrossRef Full Text | Google Scholar

96. Abbass A, Town J, Holmes H, Luyten P, Cooper A, Russell L, et al. Short-term psychodynamic psychotherapy for functional somatic disorders: a meta-analysis of randomized controlled trials. Psychother Psychosom. (2020) 2020:1–8. doi: 10.1159/000507738

PubMed Abstract | CrossRef Full Text | Google Scholar

97. Vlaeyen JWS, Crombez G, Linton SJ. The fear-avoidance model of pain. Pain. (2016) 157:1588–9. doi: 10.1097/j.pain.0000000000000574

PubMed Abstract | CrossRef Full Text | Google Scholar

Keywords: psychological factors, medically unexplained symptoms, somatoform disorders, somatic symptom disorder, depression

Citation: Mewes R (2022) Recent developments on psychological factors in medically unexplained symptoms and somatoform disorders. Front. Public Health 10:1033203. doi: 10.3389/fpubh.2022.1033203

Received: 31 August 2022; Accepted: 18 October 2022;
Published: 04 November 2022.

Edited by:

Wulf Rössler, Charité Universitätsmedizin Berlin, Germany

Reviewed by:

Paul Hüsing, University Medical Center Hamburg-Eppendorf, Germany

Copyright © 2022 Mewes. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Ricarda Mewes, ricarda.nater-mewes@univie.ac.at

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