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Predictors of Persistent Somatic Symptoms in the General Population: A Systematic Review of Cohort Studies
Open accessAbstract
Objective: Up to 10% of the general population experiences persistent somatic symptoms (PSS). Numerous studies in a variety of health domains are dedicated to identifying factors that are associated with PSS onset. The present study aimed to provide an overview of predictors for PSS onset in the general population and the related health domains. Methods: A systematic search was performed identifying longitudinal cohort studies that examined factors associated with PSS onset in the general population. Included studies measured potential predictors before PSS onset and were categorized according to the dynamic biopsychosocial model. Four levels of evidence were discerned for predictors, based on the number of studies and percentage of consistent findings. Results: In the 154 articles eligible for analysis, 27 PSS subtypes were studied, with primary focus on fibromyalgia (25.0%) and irritable bowel syndrome (23.3%). Of the >250 predictors of PSS onset, 46 were investigated more than once and showed consistent results. Strong evidence identifies biological (e.g., infections, body weight–related metrics), psychological (e.g., sleep problems, psychopathology), interpersonal (life events, childhood/interpersonal stress), contextual (employment), and health behavioral (health care utilization) predictors. Conclusions: The results provide strong evidence for factors from all dynamic biopsychosocial domains, although interpersonal and health behavioral factors are relatively under investigated. Thus, evidence suggests that reduction of predictors of PSS onset to a specific factor/domain may be too restrictive. There is no evidence that this differs per PSS subtype. Exploring all domains and measuring common factors across subtypes are essential to improve the clinical course of PSS.
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Biomedical predisposing factors that appear to be relevant across diseases include chronic medical conditions, previous somatic symptom burden, sleep disturbance, elevated body mass index, and certain genetic or epigenetic risk profiles.
“Biomedical predisposing factors that appear to be relevant across diseases include chronic medical conditions, previous somatic symptom burden, sleep disturbance, elevated body mass index, and certain genetic or epigenetic risk profiles”
From Persistent physical symptoms: definition, genesis, and management (2024) · cites this paper as [48]
The review identifies chronic medical conditions, prior somatic symptoms, sleep problems, body-weight measures, and genetic predisposition as predictors of persistent somatic symptoms (table, p. 6; discussion, p. 7). It does not establish that elevated BMI specifically increases risk—the discussion says the direction of the biometric findings was unclear—and the cited passages do not support epigenetic risk profiles. (LLM, conf=0.87)
Experimental — accuracy not yet measuredMultiple biological, psychological, and social risk factors contribute to the persistence of somatic symptoms, either individually or in combination.
“Multiple biological, psychological, and social risk factors contribute to the persistence of somatic symptoms”
From Persistent physical symptoms: definition, genesis, and management (2024) · cites this paper as [48]
The Abstract (p. 2) identifies biological, psychological, and social-domain predictors of persistent somatic symptom onset. The review does not establish that these factors cause symptoms to persist once present; the Discussion (p. 7) treats interactions between predictors as a hypothesis, not a demonstrated finding. (LLM, conf=0.86)
Experimental — accuracy not yet measuredEarly adverse life experiences, negative affectivity, neuroticism, depression, and anxiety have been identified as psychological predisposing conditions for persistent physical symptoms.
“Early adverse life experiences, negative affectivity, neuroticism, depression, and anxiety have been identified as psycho logical predisposing conditions for persistent physical symptoms”
From Persistent physical symptoms: definition, genesis, and management (2024) · cites this paper as [48]
The systematic review reports childhood adversity as a predictor of persistent somatic symptom onset (p. 5) and identifies anxiety and depression as consistent predictors (p. 5). Its predictor table (p. 6) lists childhood adversity under interpersonal factors and personality type under psychological factors, but the passages do not identify negative affectivity or neuroticism specifically. (LLM, conf=0.88)
Experimental — accuracy not yet measuredAcute infections or injuries, medical or surgical procedures, or recent stressful life events are typical triggers associated with the initial onset of short-term somatic symptoms, which might persist depending on the individual's predisposition.
“Acute infections or injuries, medical or surgical procedures, or recent stressful life events are typical triggers associated with the initial onset of shortterm somatic symptoms”
From Persistent physical symptoms: definition, genesis, and management (2024) · cites this paper as [48]
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredComorbid psychopathology can be a predictor, a concomitant factor or a consequence of CFS.
“The same applies to comorbid psychopathology, which can be a predictor [58], a concomitant factor or a consequence of CFS [12].”
From Efficacy and Acceptance of Cognitive Behavioral Therapy in Adults with Chronic Fatigue Syndrome: A Meta-analysis. (2024) · cites this paper as [58]
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“Many studies have shown that most somatic diseases result from a variety of factors, part of which are beyond the biomedical domain—thus, this is not only the case for PSS (18,19).”
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“The diagnostic distinctiveness of these syndromes in the context of PSS is debatable, because patients with syndromes, which use bodily symptoms as diagnostic criteria, often fulfill the diagnostic criteria of more than one syndrome (4,12,13).”
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“This corroborates conclusions from other research, which demonstrate that PSS requires a multidomain classification and treatment (48,49,53,54).”
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“Research in other PSS categories shows that physical activity is likely to be related to PSS in general (42,43).”
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“these days most experts accept that there are common overarching factors and syndrome-specific factors (14,15), historically, etiological research focusing on PSS is heterogeneous in nature—that is, often directed at subcategories of PSS (11).”
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“So-called PSS—symptoms without identified biomedical pathophysiology—are prevalent in both patients with well-understood disorders, such as cancer (5) and cardiovascular disease (6), as well as in patients without well-understood disorders (7–9).”
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“Although some studies show discrepancies in the association with health care utilization between PSS subtypes (40,41), our results indicate that it is associated with PSS onset across subtypes.”
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“Research in other PSS categories shows that physical activity is likely to be related to PSS in general (42,43).”
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“Diagnostic difficulties and delays may contribute to this burden (10).”
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“, cardiovascular, renal, skin, rheumatological disease) were predictive of PSS onset, which indicates that exclusion of patients with chronic medical conditions in studies investigating PSS, as done by some studies (27), is unwarranted.”
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“Although some studies show discrepancies in the association with health care utilization between PSS subtypes (40,41), our results indicate that it is associated with PSS onset across subtypes.”
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Persistent physical symptoms: definition, genesis, and management
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“The syndrome is often combined with anxiety and depression, leading to impaired social functioning, academic performance and even negative physical and psychological consequences later in life (Kitselaar et al., 2023).”
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Lipid metabolism and functional somatic disorders in the general population. The DanFunD study
Jørgensen, T., Jacobsen, R. K., Sæbye, D., Petersen, M. W., Fink, P., Gormsen, L. K., Linneberg, A. R., Bjerregaard, A. A., Schovsbo, S. U., Benros, M. E., et al. (2024) · PLoS ONE · doi:10.1371/journal.pone.0296799 · Cited by 4
“A systematic review of a variety of predictors of persistent somatic symptoms in the general population [32] identified cohort studies looking at plasma lipid and development of FSD with mixed results.”
BackgroundHahn, S., Nestoriuc, Y., Kirchhof, S., Toussaint, A. C., Löwe, B., & Pauls, F. (2025) · BMJ Open · doi:10.1136/bmjopen-2024-091032 · Cited by 5
“32 The present study thus aims to Open access provide a deeper insight into contributing factors for moment- to-moment fluctuations of somatic symptom severity, experienced by university students.”
Can the pain field learn from the functional somatic disorder field?
Gormsen, L. K., Fink, P., Butler, S. H., Henningsen, P., Loeser, J. D., Rief, W., & Finnerup, N. B. (2025) · Pain · doi:10.1097/j.pain.0000000000003733 · Cited by 3
Kahnert, S., Kämpfer, N., Ramm, M., Geiser, F., & Conrad, R. (2025) · Journal of Psychosomatic Research · doi:10.1016/j.jpsychores.2025.112381 · Cited by 3
Bos, P., Monden, R., Benraad, C. E. M., Groot, J., Voshaar, R. C. O., & Hanssen, D. J. C. (2024) · Comprehensive Psychiatry · doi:10.1016/j.comppsych.2024.152527 · Cited by 2
Petzke, T. M., Köteles, F. G., den Bergh, O. V., & Witthöft, M. (2025) · Psychosomatic Medicine · doi:10.1097/psy.0000000000001413 · Cited by 3
Chen, J., Ma, D., Cao, J., & Wei, J. (2026) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2025.1680463 · Cited by 2
“A systematic review and meta-analysis (50) showed a variety of biological, social and psychological factors had strong correlation to persistent somatic symptoms which cannot be fully attributed to objectively determined anatomical or functional disease severity (51, 52).”
Subjective and physiological reactivity to emotional stressors in somatic symptom disorder
Gitzen, H., Schmidt, J., & Martin, A. (2023) · International Journal of Psychophysiology · doi:10.1016/j.ijpsycho.2023.112273 · Cited by 2
Hoheisel, M., Popkirov, S., Michaelis, R., & Rose, M. (2024) · Complex Psychiatry · doi:10.1159/000536668 · Cited by 2
Chaabouni, A., Houwen, J., Akkermans, R., van Boven, K., Walraven, I., Blanker, M. H., Schers, H., & Hartman, T. O. (2024) · Journal of Psychosomatic Research · doi:10.1016/j.jpsychores.2024.111859 · Cited by 2
Characteristics and predictors of persistent somatic symptoms in patients with cardiac disease
Clifford, C., Löwe, B., & Kohlmann, S. (2024) · Scientific Reports · doi:10.1038/s41598-024-76554-z · Cited by 2
“Instead, psychological factors play a key role in the persistence of symptoms, which then contributes to maintaining the overall disease burden 36 .”
BackgroundAbasi, I., Ghapanchi, A., Toussaint, A. C., Bitarafan, M., Zarabi, H., Derakhshan, F. S., Derakhshan, M. K., Banihashem, S., & Derakhshan, M. A. (2024) · Current Psychology · doi:10.1007/s12144-024-06973-8 · Cited by 1
“Studies have estimated that the prevalence of persistent somatic symptoms in the general population ranges from 20 to 80% (Kitselaar et al., 2023; Kop et al., 2019), with about 5–7% being clinically diagnosed with SSD (Kur - lansik & Maffei, 2016 ; Lehmann et al., 2022).”
Hybelius, J., Hammarberg, S. A. W., Hoffmann, A. A., Spansk, E., Olsson, A., Strand, E., Winter, L. S., Åkerlund, T., Björkander, D., Kosic, A., et al. (2026) · Scientific Reports · doi:10.1038/s41598-026-50290-y · Cited by 1
Kitselaar, W. M., Hartmann, L., Evers, A. W. M., & Numans, M. E. (2026) · General Hospital Psychiatry · doi:10.1016/j.genhosppsych.2026.05.015 · Cited by 1
Self-citationDaehler, S., Lutz, W., Probst, T., Rief, W., Rubel, J. A., Schwartz, S., & Kleinstäuber, M. (2025) · Cognitive Therapy and Research · doi:10.1007/s10608-024-10571-0 · Cited by 1
“Back pain, headache, gastrointestinal symptoms and fatigue are among the most frequently reported symptoms in primary care settings of the Western world (Kitselaar et al., 2023).”
Studer, S., Nuhn, C., Weise, C., & Kleinstäuber, M. (2025) · Journal of Psychosomatic Research · doi:10.1016/j.jpsychores.2025.112069 · Cited by 1
A multidimensional longitudinal dataset on functional somatic syndromes
Adibi, P., Kalani, S., Ani, A., Shahoon, H., Feizi, A., & Roohafza, H. (2023) · Data in Brief · doi:10.1016/j.dib.2023.109267 · Cited by 1
Sirotiak, Z., Adamowicz, J. L., & Thomas, E. B. K. (2024) · Fatigue Biomedicine Health & Behavior · doi:10.1080/21641846.2024.2422258
“As most somatic syndromes are chronic, and many somatic syndromes present comorbidly [19, 49], it will be important to consider these conditions with respect to long COVID development as these syndromes may represent a long-term risk that is not unique to a particular infection (i.e. intensity of…”
Chen, B., Xie, M., Zhang, Y., Zhang, H., Yu, N. X., & Lin, D. (2024) · Applied Psychology Health and Well-Being · doi:10.1111/aphw.12638
Baranauskas, M., Kupčiūnaitė, I., Lieponienė, J., & Stukas, R. (2025) · Healthcare · doi:10.3390/healthcare13030304
Kowalski, J., Löwe, B., Schramm, C., Braun, F., Rillig, F., & Uhlenbusch, N. (2025) · Psychosomatic Medicine · doi:10.1097/psy.0000000000001403
Myles, A. B., Jones, M. P., Beath, A., Loxton, D. J., & Ejova, A. (2025) · Psychology and Health · doi:10.1080/08870446.2025.2590067
Fjellborg, K., Cervin, C., Witthöft, M., Köteles, F. G., & Nordin, S. (2025) · Journal of Psychosomatic Research · doi:10.1016/j.jpsychores.2025.112505
“A systematic review demonstrates strong support for various biological, psychological, interpersonal, contextual, and health behavioral associations with PPS in the general population [16].”
Roots of responses: A qualitative study on intergenerational transmission of illness approaches
Hogendoorn, E., van der Ziel, S., Ballering, A., van Tol, D. G., & Rosmalen, J. G. M. (2026) · International Journal of Clinical and Health Psychology · doi:10.1016/j.ijchp.2026.100692
“The occurrence of physical symptoms is multifactorial, involving a complex interplay of biological, psychological and social factors (Kitselaar et al., 2023).”
Kahnert, S. M., Jürgens, L., Dreher, L., Schmidt‐Lauber, C., Koechel, A., Frank, G. L., Huber, T. B., Mora, M. C. S., Ständer, S., Ramm, M., et al. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1804748
“As discussed above, adverse childhood experiences are a major risk factor of PSS (10 – 12).”
InfluentialJørgensen, T. S. H., Jacobsen, R. K., Jørgensen, S. W., Petersen, M. W., Bjerregaard, A. A., Gormsen, L. K., Carstensen, T. B. W., Schovsbo, S. U., Kårhus, L. L., Jørgensen, N. R., et al. (2026) · Journal of Clinical Medicine · doi:10.3390/jcm15155793
“However, the available sparse literature did not include direct measures of lipid metabolism, but merely represented more global measures of possible determinants of FSD [10,11].”
Kustra-Mulder, A., Liebau, M., Grewer, G., Rosmalen, J. G. M., Cosci, F., Rymaszewska, J., Löwe, B., & Weigel, A. (2026) · BMJ Public Health · doi:10.1136/bmjph-2025-004470
Boecking, B., Steinmetzger, K., Rose, M., Brüeggemann, P., & Mazurek, B. (2026) · Frontiers in Audiology and Otology · doi:10.3389/fauot.2026.1914013
Symptoms of depression and somatization during the Israel-Hamas War: the role of world assumptions
Greenblatt‐Kimron, L., & Lavenda, O. (2026) · Anxiety Stress & Coping · doi:10.1080/10615806.2026.2744781
Metadata
- Authors
- Kitselaar, W. M., van der Vaart, R., Perschl, J., Numans, M. E., & Evers, A. W. M.
- Affiliations
- Leiden University (NL)
- Corresponding author
- Kitselaar, Willeke M.
- ORCID
- Venue
- Psychosomatic Medicine
- Published
- 2022-10-16
- Volume
- 85
- Issue
- 1
- Pages
- 71-78
- ISSN
- 0033-3174 (ISSN-L)
- 1534-7796
- OpenAlex
- W4307848665
- Cited by
- 45
- References
- 53
- Citations by year
- 2026: 9 · 2025: 10 · 2024: 19 · 2023: 7
- FWCI
- 1.55
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Psychosomatic Medicine (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Leiden Repository (Leiden University) (submittedVersion, cc-by)
- Research Repository (Delft University of Technology) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, cc-by)
- Funders
- Universiteit Leiden
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Psychosomatic Disorders and Their Treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Fibromyalgia and Chronic Fatigue Syndrome Research
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- persistent physical symptoms, fibromyalgia, irritable bowel syndrome, biopsychosocial model, sleep disorders, psychopathology, childhood stress, interpersonal stress, life events, body weight, infection, employment, health care utilization, general population
- MeSH terms
- Medically Unexplained Symptoms, Child, Fibromyalgia, Humans, Longitudinal Studies, Cohort Studies, Irritable Bowel Syndrome
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