Mental disorders as risk factors for developing functional somatic disorder - a Danish population-based follow-up study

Mental disorders as risk factors for developing functional somatic disorder - a Danish population-based follow-up study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Mental disorders as risk factors for developing functional somatic disorder - a Danish population-based follow-up study Marie Weinreich Petersen, Tina Birgitte Wisbech Carstensen, Kaare Bro Wellnitz, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9551629/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 5 You are reading this latest preprint version Abstract Background Mental disorders and functional somatic disorder (FSD) often co-occur, but longitudinal population-based studies examining their temporal associations remain scarce. The objectives of this study were 1) to investigate the association between mental disorders and FSD in the baseline investigation of a randomly selected population-based cohort, and 2) to investigate whether mental disorders were risk factors for newly developed (incident) FSD over a 5-year period. Methods The DanFunD baseline and 5-year follow-up (FU) investigations were used. FSD comprised the outcome variables and was established at both baseline and FU with validated symptom questionnaires and diagnostic interviews. Psychiatric discharge diagnoses and prescription psychoactive medication were exposure variables and were obtained from comprehensive Danish Central Registries in a period of 10 years before study inclusion. Prevalence odds ratios (PORs) and odds ratios (ORs) with 95% confidence intervals (CIs) were measures of association. People with lived experience of FSD were not involved in the research and writing process. Results A total of 9,656 individuals participated in the DanFunD baseline cohort (53.9% women, median age 54 years, interquartile range (IQR): 44–64 years) and 5,738 individuals participated in the 5-year FU cohort (53.3% women, median age 55 years, IQR: 47–64 years). Having received a diagnosis of a mental disorder or having received prescription psychoactive medication 10 years before baseline were strongly associated with both questionnaire-based FSD (POR = 2.54, 95% CI: 2.22–2.90) and interview-diagnosed FSD (POR = 1.81, 95% CI: 1.37–2.39) at DanFunD baseline. Likewise, it was a significant risk factor for having developed FSD at FU for questionnaire-based FSD (OR = 1.60, 95% CI: 1.24–2.05). However, for interview-diagnosed FSD, a significant association could not be found (OR = 1.14, 95% CI: 0.54–2.41). Conclusions The study indicates that mental disorders may be risk factors for developing FSD. The findings suggest that effective management of mental disorders may help lower the risk of subsequent FSD, emphasizing the importance of accurate diagnosis and coordinated care across clinical services. They also point to preventive opportunities, where early psychological or stress-management interventions may benefit individuals at elevated risk. Functional Somatic Disorder Irritable Bowel Syndrome Fibromyalgia Chronic Fatigue Syndrome Mental Disorders Psychiatric Diagnoses Risk Factor Epidemiology Register-Based INTRODUCTION Functional somatic disorder (FSD) is a common condition characterized by persistent physical symptoms that cannot be better explained by other psychiatric or medical condition (1). As a unifying diagnosis, FSD encompasses many functional symptomatic syndrome diagnoses such as irritable bowel syndrome, fibromyalgia/chronic widespread pain, and chronic fatigue syndrome (2, 3). FSD is prevalent in all medical settings and the diagnosis is based on medical history and a characteristic illness pattern (1). Our knowledge about the causes of FSD is still sparse, however, it is well accepted that it has a multifactorial aetiology, comprising both biological, psychological, and social factors (4). Research on patients with severe FSD has revealed high prevalence of both physical and mental comorbidities (5, 6). A retrospective analysis of primary care claims demonstrated that mental disorders were associated with an increased likelihood of receiving a functional somatic syndrome diagnosis five years subsequently (7). Additionally, a population-based study indicated that FSD is associated with self-reported physical diseases, depression, and anxiety (3). Psychopathology has been found to predict irritable bowel syndrome and fibromyalgia, somatic symptoms, and chronic fatigue syndrome (8–12). However, the previous studies may carry some limitations: Clinical studies have used highly selected patient samples which may induce risk of selection bias, and most population-based studies have used self-report for establishing FSD diagnoses and mental disorder diagnoses which may inflict a risk of misclassification. Hence, more studies into these aspects with a sound methodology in measuring both FSD and mental disorders are needed. To address key limitations in previous research, particularly the reliance on self-reported mental health measures, the current study included data from both a baseline and follow-up measurement of a large randomly obtained Danish population cohort. Validated symptom questionnaires and diagnostic interviews were used for the establishment of FSD diagnoses. Psychiatric discharge diagnoses and prescription psychoactive medication were obtained from comprehensive Danish Central Registries in a period of 10 years before study inclusion. The objective of the current study was twofold: First, to investigate the association between mental disorders and FSD in a randomly selected population-based cohort. Second, to investigate whether mental disorders were risk factors for newly developed (incident) FSD over a 5-year period. It was hypothesized that mental disorders would be positively associated with FSD and act as risk factor for the development of incident FSD. METHODS Study population Data from two measurements of the Danish Study of Functional Disorders (DanFunD), a general population cohort, was included in the study (13): The baseline investigation, conducted in the years 2011–2015, and the 5-year follow-up (FU) investigation, conducted in year 2018–2021. Participants in the baseline investigation were randomly drawn from the Danish Civil Registration system. The exclusion criteria were: not born in Denmark, not being a Danish citizen, and pregnancy. The DanFunD baseline investigation comprises a total of 9,656 (33.7% of the invited participants) men and women aged 18–76 years born in Denmark and living in the Western part of greater Copenhagen. All participants completed questionnaires about physical and mental health, among others. A stratified subsample (n = 2,450) including every tenth participant and all participants with high symptom scores on the DanFunD baseline symptom questionnaires were invited to participate in a diagnostic interview (the Research Interview for Functional somatic Disorders (RIFD)), performed by trained family physicians (14). The RIFD interview was developed from the large Schedules of Clinical Assessment in Neuropsychiatry. A total of 1,590 (64.9%) participants accepted and participated in the interview. For the 5-year FU investigation, 7,289 participants from the baseline cohort were invited and 5,738 (78.7%) accepted. Of them, 1,452 were invited to participate in a second RIFD interview; 1,092 (75.2%) accepted. Measures The primary exposure variables were mental disorders which were established in two ways: Inpatient and outpatient hospital discharge diagnoses of mental disorders were identified in the Danish National Patient Registry according to the 10th revision of the International Classification of Diseases (ICD-10) within a time frame of 10 years before DanFunD inclusion. The Danish National Patient Registry is a population-based administrative registry, which has collected data from all public Danish hospitals since 1977 with complete nationwide coverage since 1978 (15). Denmark runs a nationwide centralized register of personal information, the Civil Registration System, for which purpose every citizen is given a unique personal identification number. All public registries in Denmark, including the Danish National Patient Registry, use this unique number, which allows linkage of registers and of trial data to register data (16). The included mental discharge diagnoses were grouped in overall categories and are displayed in Table 1 in the Supplemental Materials. In the statistical analyses, exposure variables of mental disorders constituted an overall category of mental disorder, i.e. having received at least one of the diagnoses. Table 1 Descriptives of the complete study sample (n = 9,656) at baseline Women; N (%) No FSD (n = 7,325) Overall FSD (n = 1,543) Single-organ FSD (n = 1,447) Multi-organ FSD (n = 96) IB (n = 337) CWP (n = 442) CF (n = 823) 3,666 (50.05) 1,041 (67.47) 967 (66.83) 74 (77.08) 252 (74.78) 342 (77.38) 576 (69.99) Age at baseline; median (IQR) 54 (44–64) 55 (46–63) 55 (47–63) 51 (42–58) 50 (40–60) 58 (50–65) 50 (40–59) Social status; median (IQR) 7 (6–8) 6 (5–7) 6 (5–7) 6 (5–7) 6 (5–7) 6 (5–7) 6 (5–7) Physical comorbidity; N (%) 384 (5.24) 150 (9.72) 138 (9.54) 12 (12.50) 24 (7.12) 51 (11.54) 72 (8.75) Neuroticism; median (IQR) 15 (10–19) 20 (15–26) 20 (15–26) 26.5 (22–32) 22 (16–27) 20 (15–26) 24 (18–29) At least one psychiatric discharge diagnosis; N (%) 158 (2.16) 120 (7.78) 98 (6.77) 22 (22.92) 31 (9.20) 27 (6.11) 80 (9.72) Anxiety disorder 25 (0.34) 27 (1.75) 22 (1.52) 5 (5.21) 8 (2.37) 5 (1.13) 17 (2.07) Depression 48 (0.66) 50 (3.24) 37 (2.56) 13 (13.54) 11 (3.26) 11 (2.49) 37 (4.50) Personality disorder 5 (0.07) 14 (0.91) 10 (0.69) 4 (4.17) 9 (2.67) 3 (0.68) 12 (1.46) Stress-related disorder 77 (1.05) 50 (3.24) 40 (2.76) 10 (10.42) 15 (4.45) 11 (2.49) 32 (3.89) Use of prescription psychoactive medication (any); N (%) 782 (10.68) 549 (35.58) 485 (33.52) 64 (66.67) 112 (33.23) 184 (41.63) 325 (39.49) Prescription for antidepressive and/or anxiolytics 745 (10.17) 545 (35.32) 481 (33.24) 64 (66.67) NA 184 (41.63) NA At least one diagnosis or use of prescription psychoactive medication; N (%) 848 (11.58) 565 (36.62) 499 (34.49) 66 (68.75) 119 (35.31) 185 (41.86) 342 (41.56) Abbreviations: FSD = functional somatic disorder; IB = irritable bowel; CWP = chronic widespread pain; CF = chronic fatigue; FSD, IB, CWP, and CF are established by means of self-reported questionnaires. Psychiatric discharge diagnoses and prescription psychoactive medication are obtained from National Danish Registries within a 10 year period before baseline. NA = not applicable because number of events were 0 or adjustment was not feasible as number of cases became too low for obeying the Statistics Denmark’s requirements for statistical disclosure control in relation to personal data. Prescriptions of psychoactive medication included prescriptions from both hospitals and primary care and were identified from the Danish National Prescription Registry (17) within a time frame of 10 years before DanFunD inclusion. The Danish National Prescription Registry receives data recorded in the electronic dispensing systems of community pharmacies. The registry contains information about each redeemed prescription, including those describing the patient, the drug dispensed, the health provider issuing the prescription and the dispensing pharmacy. The included prescription psychoactive medication is displayed in Table 1 in the Supplemental Materials. In the statistical analyses, exposure variables of prescription psychoactive medication constituted an overall category of prescription psychoactive medication, i.e. having received at least one of the prescription psychoactive medications. Secondary exposure variables constituted age, sex, subjective social status, physical comorbidities, and neuroticism. Subjective social status was measured with one item at baseline asking the participants to rate their own social status on a scale from 1 to 10, with 1 being the lowest and 10 being the highest status in society (18). Physical disease was measured in a 10-year period before a participant's inclusion in DanFunD baseline and defined as having at least one of the conditions included in the updated version of the Charlson Comorbidity Index by Quan et al. (19) which is recommended for use with contemporary administrative and register-based data. Diagnoses of these conditions was identified through the Danish National Patient Registry (15). Neuroticism was measured at baseline with the Danish version of the short-form NEO Personality Inventory (NEO-PI-Rsf), which has been validated in a large sample from the Danish population and shown acceptable psychometric properties in terms of internal consistency and reliability (20). The domain for neuroticism was scored from 0 to 48, with a higher score indicating higher levels of neuroticism. Outcomes The unifying diagnostic construct of Bodily Distress Syndrome was used for the primary operationalisation of FSD. The construct presents with four symptom clusters; cardiopulmonary, gastrointestinal, musculoskeletal, general symptoms/fatigue, and divides patients with FSD into two types: a single-organ type, i.e., individuals with symptoms from one or two of the symptom clusters, and a multi-organ type, i.e., individuals with symptoms from at least three of the four symptom clusters. In this paper, the primary definition of FSD was the Bodily Distress Syndrome diagnostic concept. Additionally, we also included definitions of the three functional somatic syndromes: irritable bowel (IB), chronic widespread pain (CWP), and chronic fatigue (CF). The assessment of FSD was conducted both at baseline and at the 5-year FU investigation. Cases with FSD (single- and multi-organ type) were identified by the self-reported Bodily Distress Syndrome Checklist (21), including bothersome symptoms within the last 12 months. Additionally, a stratified subsample of participants with a clinical diagnosis of FSD was identified by means of a diagnostic interview, developed to be used as a second phase tool after a respondent’s self-report in symptom questionnaires (14). The diagnostic interviews were performed by trained primary care physicians over the phone. The physicians assessed whether a specific symptom pattern was due to an FSD rather than another physical or mental condition. The diagnostic interview has shown good criterion validity for identifying individuals with FSD (14). Individuals fulfilling criteria for IB (22), CWP (23), and CF (24) were identified with self-reported validated symptom questionnaires including bothersome symptoms within the last 12 months. Statistical analyses All analyses were performed using STATA version 18.0 (25). Descriptive statistics were shown with number and percentages for categorical variables and medians with interquartile ranges (IQR) for continuous variables due to skewness of the data. For testing of the hypothesis that mental disorders were associated with having FSD at baseline, three sets of logistic regression models were conducted for each FSD definition. For all three sets of analyses, FSD case status at baseline was the outcome variable and separate analyses were conducted for FSD established with self-reported questionnaires and FSD diagnosed with diagnostic interviews: 1 = FSD present, 0 = FSD not present (controls). For the three different sets of analyses, three different variables for mental disorders received within a period of 10 years before baseline constituted the exposure variable: In the first set of analyses, the exposure variable constituted register-based overall psychiatric discharge diagnoses (at least one: yes = 1, no = 0); in the second set of analyses, the exposure variable constituted prescription psychoactive medicine (at least one: yes = 1, no = 0); and in the third set of analyses, the exposure variable constituted overall psychiatric discharge diagnoses and/or prescription psychoactive medicine (at least one: yes = 1, no = 0). Prevalence odds ratios (PORs) with 95% confidence intervals (CIs) were used as measure of associations. A POR > 1 supported an association in the expected direction. For testing of the hypothesis that mental disorders were risk factors for having developed incident FSD at FU, three sets of logistic regression models were conducted in the same manner as for the above analyses. In these analyses, incident FSD at follow-up, i.e. no FSD at baseline, was the outcome variable. Separate analyses were conducted for incident FSD established with self-reported questionnaires and incident FSD diagnosed with diagnostic interviews: 1 = FSD present, 0 = FSD not present (controls). Odds ratios (ORs) with 95% CI were used as measure of association. An OR > 1 supported an association in the expected direction. Potential confounders were identified using directed acyclic graphs (DAGs) constructed in the browser-based programme DAGitty Version 3.0 (26). Two models were constructed: The first controlled for baseline levels of sex, age, social status, and physical comorbidity. The second additionally controlled for baseline neuroticism to assess how important a confounder this was. Linearity of age, social status, and neuroticism was visually checked by expanding the model with each independent variable introduced as natural cubic splines with five knots at the 5th, 27.5th, 50th, 72.5th, and 95th percentiles. In all models, assumption of linearity was deemed acceptable, hence, and age, social status, and neuroticism were included as linear variables in all analyses. In addition to unstratified analyses, sex and age stratified analyses were conducted using the same modelling procedure. RESULTS The baseline sample comprised 9,656 participants (53.88% women) with a median age at baseline of 54 (IQR: 44–64) years. Median social status was 7 (IQR: 6–8), 584 (6.05%) had a physical condition, and the median level of neuroticism was 16 (IQR: 11–21). The proportion of study participants who had received a psychiatric diagnosis at discharge from a psychiatric department within the last 10 years before baseline was 326 (3.38%) while 1,526 (15.80%) had prescribed psychoactive medication. Compared to controls, a larger fraction of participants with FSD according to the questionnaires had received a diagnosis of a mental disorder (7.8% vs 2.16%) or been prescribed psychoactive medication (35.6% vs 10.7 (Table 1 ). Also, compared to controls, a larger fraction of participants with overall FSD, diagnosed with the interview, had received a diagnosis of a mental disorder (11.4% vs 4.1%) or been prescribed psychoactive medication (40.8% vs 20.7% (Table 2 ). Table 2 Descriptives of the interviewed study sample (n = 1,590) at baseline Women; N (%) No FSD (n = 1,159) Overall FSD (n = 412) Single-organ FSD (n = 326) Multi-organ FSD (n = 86) 633 (54.62) 299 (72.57) 228 (69.94) 71 (82.56) Age at baseline; median (IQR) 55 (45–64) 51 (42–59) 51 (42–60) 48.5 (39.5–57) Social status; median (IQR) 7 (6–8) 6 (5–7) 6 (5–7) 6 (5–7) Physical comorbidity; N (%) 110 (9.49) 24 (5.83) 20 (6.13) 4 (4.65) Neuroticism; median (IQR) 16 (11–22) 23.5 (17–29) 23 (16–28) 26 (18–32) At least one psychiatric diagnosis; N (%) 47 (4.06) 47 (11.41) 35 (10.74) 12 (13.95) Anxiety disorder 11 (0.95) 15 (3.64) 10 (3.07) 5 (5.81) Depression 19 (1.64) 23 (5.58) 17 (5.21) 6 (6.98) Personality disorder 6 (0.52) 7 (1.70) 4 (1.23) 3 (3.49) Stress-related disorder 20 (1.73) 15 (3.64) 10 (3.07) 5 (5.81) Use of prescription psychoactive medication (any); N (%) 240 (20.71) 168 (40.78) 127 (38.96) 41 (47.x) Prescription for antidepressive and/or anxiolytics 235 (20.3) NA NA 41 (47.67) At least one diagnosis or use of prescription psychoactive medication; N (%) 248 (21.40) 173 (41.99) 130 (39.88) 43 (50.00) Abbreviations: FSD = functional somatic disorder. FSD is diagnosed with diagnostic interviews performed by trained family physicians. Psychiatric discharge diagnoses and prescription psychoactive medication are obtained from National Danish Registries within a 10 year period before baseline. NA = not applicable because number of events were 0 or adjustment was not feasible as number of cases became too low for obeying the Statistics Denmark’s requirements for statistical disclosure control in relation to personal data. The FU sample comprised 5,738 participants (53.33% women) with a median age of 55 (IQR: 47–64). Median social status was 7 (IQR: 6–8), 329 (5.73%) had a physical condition, and the median level of neuroticism was 15 (IQR: 11–20). The proportion of study participants who had received a psychiatric diagnosis at discharge from a psychiatric department within the last 10 years before baseline was 149 (2.60%) while 775 (13.51%) had prescribed psychoactive medication. More detailed information about the FU samples is displayed in the Supplemental Materials, Tables S2-S3. Table 3 presents the associations between mental disorders and FSD at baseline. For most cases, strong associations emerged with having received a psychiatric diagnosis or a prescription for psychiatric medication within a time period of 10 years before baseline. However, associations with having received at psychiatric diagnosis became insignificant for questionnaire-based IB, CWP, and CF in model 2 with additional adjustment for neuroticism. The same was the case for interview-diagnosed FSD. Notably, in the fully adjusted model, the odds of having multi-organ FSD defined by questionnaires were significantly elevated for individuals having received a psychiatric diagnosis (POR = 2.91, 95% CI: 1.60–5.31) or prescription for psychiatric medication (POR = 6.08, 95% CI: 3.78–9.78). Table 3 Association between mental disorders and use of prescription medicine and functional somatic disorder at baseline At least one diagnosis or use of prescription psychoactive medication POR (95% CI) At least one psychiatric diagnosis POR (95% CI) Use of prescription psychoactive medication (any) POR (95% CI) Cases established by self-reported symptom questionnaires at baseline Overall FSD (n = 1,543) 1 3.36 (2.96–3.82) 2.69 (2.10–3.45) 3.50 (3.08–3.98) Overall FSD (n = 1,543) 2 2.54 (2.22–2.90) 1.78 (1.36–2.32) 2.64 (2.30–3.02) Single-organ FSD (n = 1,447) 1 3.10 (2.72–3.53) 2.38 (1.83–3.10) 3.23 (2.83–3.69) Single-organ FSD (n = 1,447) 2 2.39 (2.09–2.75) 1.64 (1.24–2.17) 2.49 (2.16–2.86) Multi-organ FSD (n = 96) 1 11.52 (7.36–18.03) 6.66 (3.87–11.47) 11.67 (7.48–18.19) Multi-organ FSD (n = 96) 2 6.07 (3.76–9.81) 2.91 (1.60–5.31) 6.08 (3.78–9.78) IB (n = 337) 1 3.14 (2.47–3.99) 2.70 (1.78–4.08) 3.18 (2.49–4.06) IB (n = 337) 2 2.10 (1.62–2.72) 1.53 (0.98–2.38) 2.10 (1.61–2.73) CWP (n = 442) 1 3.70 (3.00-4.56) 1.96 (1.26–3.06) 3.90 (3.16–4.80) CWP (n = 442) 2 2.90 (2.33–3.61) 1.20 (0.75–1.92) 3.05 (2.44–3.80) CF (n = 823) 1 4.06 (3.46–4.77) 2.69 (2.01–3.59) 4.18 (3.55–4.93) CF (n = 823) 2 2.48 (2.08–2.95) 1.27 (0.92–1.76) 2.53 (2.11–3.02) Cases established with diagnostic interviews at baseline Overall FSD (n = 412) 1 2.45 (1.89–3.17) 2.14 (1.36–3.37) 2.49 (1.91–3.24) Overall FSD (n = 412) 2 1.81 (1.37–2.39) 1.39 (0.86–2.24) 1.84 (1.39–2.44) Single-organ FSD (n = 326) 1 2.29 (1.73–3.03) 2.15 (1.32–3.49) 2.34 (1.76–3.11) Single-organ FSD (n = 326) 2 1.75 (1.30–2.36) 1.48 (0.89–2.45) 1.79 (1.32–2.42) Multi-organ FSD (n = 86) 1 3.24 (2.00-5.25) 2.22 (1.03–4.78) 3.18 (1.96–5.17) Multi-organ FSD (n = 86) 2 2.00 (1.18–3.39) 1.18 (0.52–2.69) 1.97 (1.17–3.35) Logistic regression analyses: 1 adjusted for baseline levels of age, sex, social status, and physical comorbidity; 2 additional adjustment for baseline levels of neuroticism. Abbreviations: FSD = functional somatic disorder; IB = irritable bowel; CWP = chronic widespread pain; CF = chronic fatigue; POR = prevalence odds ratio; CI = confidence interval Sex-stratified analyses of the association between mental disorders and questionnaire-based FSD at baseline showed no substantial differences between men and women. However, no associations were observed in men between interview-diagnosed FSD and mental disorder (Table S4). Age-stratified analyses similarly showed no major differences across age groups; however, for interview-diagnosed FSD, associations were generally not significant in the youngest age group (18–39 years) (Table S5). Table 4 outlines the associations between mental disorders and incident FSD at follow-up. For questionnaire-based incident cases of FSD, strong associations were found besides from the multi-organ FSD type. The absence of a significant association for multi-organ FSD may, however, be attributed to the small number of cases (n = 29) which also made adjustment for neuroticism in model 2 not feasible. Strong associations were found for CWP and CF in most cases. However, for IB, no significant associations were found. For cases of newly developed FSD established by diagnostic interviews, associations were found between having received prescriptions for psychiatric medication and overall FSD in model 1 (OR = 2.22, 95% CI: 1.12–4.42). Also, associations were found between multi-organ FSD and having received a psychiatric diagnosis or a prescription for psychiatric medication (OR = 4.38, 95% CI: 1.15–16.67). However, analyses on interview-established multi-organ FSD were not adjusted owing to insufficient case numbers (n = 9). Table 4 Mental disorders as risk factor for developing functional somatic disorder at follow-up At least one diagnosis or use of prescription psychoactive medication OR (95% CI) At least one psychiatric diagnosis OR (95% CI) Use of prescription psychoactive medication (any) OR (95% CI) Incident cases established by self-reported symptom questionnaires at follow-up Overall FSD (n = 548) 1 1.95 (1.53–2.47) 2.54 (1.56–4.12) 1.97 (1.54–2.52) Overall FSD (n = 548) 2 1.60 (1.24–2.05) 1.90 (1.15–3.14) 1.60 (1.24–2.07) Single-organ FSD (n = 519) 1 1.98 (1.56–2.53) 2.69 (1.65–4.36) 2.00 (1.56–2.57) Single-organ FSD (n = 519) 2 1.68 (1.31–2.17) 2.07 (1.25–3.41) 1.69 (1.30–2.19) Multi-organ FSD (n = 29) 1 1.85 (0.70–4.88) NA 2.02 (0.76–5.35) Multi-organ FSD (n = 29) 2 NA NA NA IB (n = 105) 1 1.46 (0.86–2.48) 1.24 (0.44–3.54) 1.38 (0.79–2.40) IB (n = 105) 2 1.22 (0.70–2.11) 0.91 (0.31–2.68) 1.13 (0.63–2.01) CWP (n = 190) 1 2.02 (1.40–2.91) 2.15 (1.01–4.59) 1.98 (1.37–2.87) CWP (n = 190) 2 1.89 (1.30–2.76) 1.80 (0.83–3.92) 1.85 (1.26–2.72) CF (n = 257) 1 2.52 (1.86–3.43) 2.23 (1.25–3.97) 2.49 (1.81–3.43) CF (n = 257) 2 1.80 (1.30–2.50) 1.36 (0.74–2.51) 1.74 (1.24–2.44) Incident cases established with diagnostic interviews at follow-up Overall FSD (n = 59) 1 1.87 (0.95–3.71) 1.81 (0.52–6.27) 2.22 (1.12–4.42) Overall FSD (n = 59) 2 1.14 (0.54–2.41) 1.01 (0.27–3.76) 1.39 (0.66–2.93) Single-organ FSD (n = 50) 1 1.48 (0.69–3.18) 1.39 (0.34–5.66) 1.79 (0.83–3.88) Single-organ FSD (n = 50) 2 NA NA NA Multi-organ FSD (n = 9) 1 4.38 (1.15–16.67)* NA NA Multi-organ FSD (n = 9) 2 NA NA NA Logistic regression analyses: 1 adjusted for baseline levels of age, sex, social status, and physical comorbidity; 2 additional adjustment for baseline levels of neuroticism. * Not adjusted due to the low number of cases, in order to avoid overfitting. Abbreviations: FSD = functional somatic disorder; IB = irritable bowel; CWP = chronic widespread pain; CF = chronic fatigue; OR = odds ratio; CI = confidence interval;. NA = not applicable because number of events were 0 or adjustment was not feasible as number of cases became too low for obeying the Statistics Denmark’s requirements for statistical disclosure control in relation to personal data. Sex-stratified analyses of the association between mental disorders and incident FSD at follow-up indicated generally weaker associations in men than in women (Table S6). Age-stratified analyses showed no consistent pattern of associations across age groups for either questionnaire-based or interview-diagnosed cases (Table S7). DISCUSSION In this prospective population-based follow-up study using historical prospective collected exposure data, we found strong associations between mental disorders and most cases of FSD, including IB, CWP, and CF. Mental disorders were identified as a significant risk factor for developing these conditions over a 5-year follow-up period, however, when adjusting for neuroticism, some of these associations attenuated. Importantly, our study design allowed for a robust investigation of these associations by combining multiple data sources, including Danish health registers and diagnostic interviews on FSD. These results are in line with studies in clinical setting and advance previous population-based studies pointing to psychopathology being a predictor for self-reported irritable bowel syndrome and fibromyalgia, somatic symptoms, and chronic fatigue syndrome (6–12). More research is needed to fully understand the association between FSD and mental disorders, but it is widely held that the aetiologies for both are multifactorial, and the conditions thus may share common mechanisms including genetic dispositions (27, 28). Both bodily distress, depressed mood and anxiety are common reaction to stress, distressing feelings, thoughts etc. Despite individuals may be prone to one type of reaction, responses is often mixed and may vary over time, which might facilitate the association. Heightened attention to bodily sensations, somatosensory amplification, and negative cognitive appraisal are suggested in both anxiety and depressive disorders as well as in FSD; it has been shown that neuroticism is a risk factor for both FSD and mental disorders (29, 30). FSD may also be a reaction to bodily stress, i.e. after severe infections, physical trauma, or surgery. This may be mediated through immune activation, and immune dysregulation which has also been implicated in mental disorders (31, 32). Altered autonomic regulation and neurohormonal activity have been reported in both FSD and mental disorders, why these physiological mechanisms may be a common denominator (33, 34). Early-life adversity, psychological trauma, and chronic stress are also established risk factors for both FSD and common mental disorders (35, 36). The high comorbidity between FSD and mental disorders and the increased risk of developing FSD when having a mental disorder may have important clinical implications: First, it challenges the “either–or” thinking which is often met in clinical practice and research, conceptualising FSD and functional somatic syndromes as purely a somatic condition. Second, the results suggest that timely and effective identification and treatment of mental disorders may play a preventive role in reducing the onset or severity of FSD. This underlines the importance of routine examination for anxiety, depression, and other mental disorders in patients with FSD. Strengthening diagnostics in primary care and non-psychiatric settings may therefore improve patient trajectories by ensuring that relevant psychiatric comorbidities are detected early and addressed systematically. Third, this study underlines the importance of psychiatric and psychological expertise presented in specialised FSD settings and supports close cooperation with general psychiatry. Finally, recognising mental disorders as risk factors for FSD may inform prevention strategies. Taken together, these clinical implications suggest that acknowledging the role of mental disorders in the development of FSD may lead to more accurate diagnosis, better prevention, more comprehensive treatment, and ultimately more compassionate and patient-centered care. While the hypothesis that psychopathology is a risk factor for developing FSD seems evident, some studies also point to a bidirectional relationship between psychopathology and functional gastrointestinal disorders and fibromyalgia, respectively (37, 38). To investigate if psychopathology is a consequence of FSD require a setup with a long time frame of prospective data on psychiatric discharge diagnoses and psychoactive medication to ensure that the FSD was present at first. It was therefore not feasible to make these conclusions on the basis of the current study. However, mental disorders and FSD are likely to be linked through bidirectional causal pathways. Further studies are therefore needed to establish this finding. The response rates of 29.5% for the baseline cohort and 78.7% for the 5-year follow-up investigation may have induced a risk of selection bias. For the baseline investigation, a non-responder analysis has shown that selection bias did not seem to noticeably influence the social parameters (39). However, the non-responder analysis for the 5-year FU investigation from the current study showed that the non-responders had a higher proportion of FSD than responders. This selection bias could potentially bias the obtained results towards an underestimation of the associations to mental disorders. Most recent data for the present study are on average at least six years old. Changes in mental health service use, treatment patterns, or diagnostic practice since that time may limit the contemporaneous relevance of absolute estimates, although the relative associations reported are likely to be robust to such temporal shifts. Registry diagnoses and prescription data reduce recall bias but may overlook subtle or dynamic mental-health and somatic symptom presentations. FSD were defined according to a common classification framework of single- and multi-organ types, encompassing chronic widespread pain, irritable bowel, and chronic fatigue. Analyses considered both overall FSD (single- and multi-organ) and specific somatic syndromes to explore potential differences. The distinction between single- and multi-organ FSD is clinically relevant, reflecting variation in symptom distribution and complexity, and allows assessment of whether mental disorders act as a general risk factor across the FSD spectrum. Although analyses of specific psychiatric diagnoses would be informative, limited event numbers in this population-based sample restricted statistical power. Therefore, mental disorders were analyzed as a combined category, with distributions of some specific diagnoses provided only descriptively. Logistic regression was used because the timing of incident FSD could not be determined with sufficient precision. FSD was assessed at follow-up based on symptoms reported for the preceding 12 months, meaning onset could have occurred at any point during this period. This results in substantial uncertainty and interval censoring of the outcome, making time-to-event analyses such as Cox regression difficult to interpret. Assigning arbitrary event times would risk misclassification without improving inference; therefore, logistic regression was considered more appropriate. The number of incident cases was low for some of the FSD categories, especially for the multi-organ type. It was therefore not possible to adjust for relevant confounders in these cases. In order to emphasise the results from the current study, similar analyses adjusted for confounding may preferably be replicated in future studies with a larger data material. Conclusions Mental disorders are strongly associated with FSD, IB, CWP, and CF, and they may be risk factors for developing these conditions. Recognising the close association between mental disorders and FSD may have important clinical implications such as more accurate diagnosis, better prevention, and more effective treatment. Declarations Ethical statement The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committees on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008. All procedures were approved by the Ethical Committee of the Capital Region (H-3-2011-081, H-3-2012-015), and all participants gave written informed consent. Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests. Funding This work was supported by grants from the Lundbeck Foundation [grant number R155-2013-14070] and the TrygFonden [grant numbers 7-11-0213 and 153171). The funding sources had no involvement in the study design; in the collection, analysis, and interpretation of data; in the writing of the paper; and in the decision to submit the paper for publication. Author Contribution MWP, KBW, TWC, EØ, and PF contributed to the conception and design of the study. MWP, KBW, and EØ accessed and verified the data and performed the analyses. MWP interpreted the data and drafted the article. KBW, TWC, EØ, TMD, LF, LFE, and PF contributed to the interpretations of the data. All authors discussed the results and contributed to critically revising the article for important intellectual content. All authors read and approved the final version of the article. Acknowledgement During the preparation of this work the authors used ChatGPT for some parts of the manuscript in order to improve language and readability. After using this tool, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication. Data Availability Data collected for the study are not available because of Danish data protection regulations.Study registration: ClinicalTrials.gov: NCT06006715. References Burton C, Fink P, Henningsen P, Lowe B, Rief W. Functional somatic disorders: discussion paper for a new common classification for research and clinical use. BMC Med. 2020;18(1):34. Fink P, Schröder 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(5):415-26. Petersen MW, Schröder A, Jørgensen T, Ørnbøl E, Meinertz Dantoft T, Eliasen M, et al. Irritable bowel, chronic widespread pain, chronic fatigue and related syndromes are prevalent and highly overlapping in the general population: DanFunD. Scientific reports. 2020;10(1):3273-. Kleinstäuber M, Schröder A, Daehler S, Pallesen KJ, Rask CU, Sanyer M, et al. Aetiological Understanding of Fibromyalgia, Irritable Bowel Syndrome, Chronic Fatigue Syndrome and Classificatory Analogues: A Systematic Umbrella Review. Clinical Psychology in Europe. 2023;5(3):1-25. Petersen MW, Skovenborg EL, Rask CU, Hoeg MD, Ornbol E, Schroder A. Physical comorbidity in patients with multiple functional somatic syndromes. A register-based case-control study. Journal of psychosomatic research. 2018;104:22-8. Schröder A, Rehfeldt E, Ørnbøl E, Sharpe M, Licht RW, Fink P. Cognitive-behavioural group treatment for a range of functional somatic syndromes: randomised trial. Br J Psychiatry. 2012;200(6):499-507. Donnachie E, Schneider A, Enck P. Comorbidities of Patients with Functional Somatic Syndromes Before, During and After First Diagnosis: A Population-based Study using Bavarian Routine Data. Sci Rep. 2020;10(1):9810. Creed F. The risk factors for self-reported fibromyalgia with and without multiple somatic symptoms: The Lifelines cohort study. J Psychosom Res. 2022;155:110745. Creed F. Psychiatric disorders and the onset of self-reported fibromyalgia and chronic fatigue syndrome: The lifelines cohort study. Front Psychiatry. 2023;14:1120250. Creed F. Review article: the incidence and risk factors for irritable bowel syndrome in population-based studies. Aliment Pharmacol Ther. 2019;50(5):507-16. Creed F. The predictors of somatic symptoms in a population sample: The Lifelines cohort study. Psychosomatic Medicine. 2022:10.1097/PSY.0000000000001101. Creed F. Psychiatric disorders comorbid with general medical illnesses and functional somatic disorders: The Lifelines cohort study. PLoS One. 2023;18(5):e0286410. Dantoft TM, Ebstrup JF, Linneberg A, Skovbjerg S, Madsen AL, Mehlsen J, et al. Cohort description: The Danish Study of Functional Disorders. Clin Epidemiol. 2017;9:127-39. Petersen MW, Schroder A, Jorgensen T, Ornbol E, Dantoft TM, Eliasen M, et al. RIFD - A brief clinical research interview for functional somatic disorders and health anxiety. Journal of psychosomatic research. 2019. Schmidt M, Schmidt SA, Sandegaard JL, Ehrenstein V, Pedersen L, Sorensen HT. The Danish National Patient Registry: a review of content, data quality, and research potential. Clinical epidemiology. 2015;7:449-90. Schmidt M, Pedersen L, Sorensen HT. The Danish Civil Registration System as a tool in epidemiology. European journal of epidemiology. 2014;29(8):541-9. Pottegard A, Schmidt SAJ, Wallach-Kildemoes H, Sorensen HT, Hallas J, Schmidt M. Data Resource Profile: The Danish National Prescription Registry. International journal of epidemiology. 2017;46(3):798-f. Singh-Manoux A, Adler NE, Marmot MG. Subjective social status: its determinants and its association with measures of ill-health in the Whitehall II study. Soc Sci Med. 2003;56(6):1321-33. Quan H, Li B, Couris CM, Fushimi K, Graham P, Hider P, et al. Updating and validating the Charlson comorbidity index and score for risk adjustment in hospital discharge abstracts using data from 6 countries. American Journal of Epidemiology. 2011;173(6):676-82. Costa PJ, McCrae R. Revised NEO Personality Inventory (NEO-PI-R) and NEO Five-Factor Inventory (NEO-FFI) professional manual. Odessa, FL: Psychological Assessment Ressources. 1992. Budtz-Lilly A, Fink P, Ornbol E, Vestergaard M, Moth G, Christensen KS, et al. A new questionnaire to identify bodily distress in primary care: The 'BDS checklist'. Journal of psychosomatic research. 2015;78(6):536-45. Kay L, Jorgensen T. Redefining abdominal syndromes. Results of a population-based study. Scandinavian Journal of Gastroenterology. 1996;31(5):469-75. White KP, Harth M, Speechley M, Ostbye T. Testing an instrument to screen for fibromyalgia syndrome in general population studies: the London Fibromyalgia Epidemiology Study Screening Questionnaire. The Journal of rheumatology. 1999;26(4):880-4. Chalder T, Berelowitz G, Pawlikowska T, Watts L, Wessely S, Wright D, et al. Development of a fatigue scale. Journal of psychosomatic research. 1993;37(2):147-53. StataCorp. Stata Statistical Software: Release 18. In: College Station TSL, editor. 2023. Textor J, van der Zander B, Gilthorpe MS, Liskiewicz M, Ellison GT. Robust causal inference using directed acyclic graphs: the R package 'dagitty'. Int J Epidemiol. 2016;45(6):1887-94. Grotzinger AD, Werme J, Peyrot WJ, Frei O, de Leeuw C, Bicks LK, et al. Mapping the genetic landscape across 14 psychiatric disorders. Nature. 2025. Kendler KS, Ohlsson H, Neale M, van Loo H, Rosmalen JGM, Sundquist J, et al. A multivariate Swedish national twin-sibling study in women of major depression, anxiety disorder, fibromyalgia, and irritable bowel syndrome. Psychol Med. 2025;55:e125. Ormel J, Jeronimus BF, Kotov R, Riese H, Bos EH, Hankin B, et al. Neuroticism and common mental disorders: meaning and utility of a complex relationship. Clin Psychol Rev. 2013;33(5):686-97. Lamm TT, Von Schrottenberg V, Rauch A, Bach B, Pedersen HF, Rask MT, et al. Five-factor personality traits and functional somatic disorder: A systematic review and meta-analysis. Clin Psychol Rev. 2025;115:102529. Schovsbo SU, Møllehave LT, Petersen MW, Ahrendt Bjerregaard A, Eliasen M, Pedersen SB, et al. Association between infections and functional somatic disorders: a cross-sectional population-based cohort study. BMJ Open. 2022;12(11):e066037. Mousten IV, Sørensen NV, Christensen RHB, Benros ME. Cerebrospinal Fluid Biomarkers in Patients With Unipolar Depression Compared With Healthy Control Individuals: A Systematic Review and Meta-analysis. JAMA Psychiatry. 2022;79(6):571-81. Gormsen L, Mølgaard H, Dantoft TM, Bjerregaard AA, Fink P, Petersen MW. Autonomic arousal and heart rate variability in functional somatic disorder - a cross-sectional population-based study. Journal of Psychosomatic Research. 2025;196:112193. Van Den Houte M, Ramakers I, Van Oudenhove L, Van den Bergh O, Bogaerts K. Comparing autonomic nervous system function in patients with functional somatic syndromes, stress-related syndromes and healthy controls. Journal of Psychosomatic Research. 2025;189:112025. Petersen MW, Carstensen TBW, Wellnitz KB, Ørnbøl E, Frostholm L, Dantoft TM, et al. Neuroticism, perceived stress, adverse life events and self-efficacy as predictors of the development of functional somatic disorders: longitudinal population-based study (DanFunD). BJPsych Open. 2024;10(1):e34. Jacobsen SA, Petersen MW, Wellnitz KB, Ørnbøl E, Dantoft TM, Jørgensen T, et al. Functional Somatic Disorders in Individuals With a History of Sexual Assault. JAMA Psychiatry. 2025. Chang MH, Hsu JW, Huang KL, Su TP, Bai YM, Li CT, et al. Bidirectional Association Between Depression and Fibromyalgia Syndrome: A Nationwide Longitudinal Study. J Pain. 2015;16(9):895-902. Koloski NA, Jones M, Kalantar J, Weltman M, Zaguirre J, Talley NJ. The brain--gut pathway in functional gastrointestinal disorders is bidirectional: a 12-year prospective population-based study. Gut. 2012;61(9):1284-90. Schovsbo SU, Dantoft TM, Thuesen BH, Leth-Møller KB, Eplov LF, Petersen MW, et al. Social position and functional somatic disorders: The DanFunD study. Scand J Public Health. 2021:14034948211056752. Additional Declarations No competing interests reported. Supplementary Files SupplementalMaterialsBMCMedicine.docx Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 14 May, 2026 Reviewers invited by journal 29 Apr, 2026 Editor assigned by journal 29 Apr, 2026 Submission checks completed at journal 29 Apr, 2026 First submitted to journal 28 Apr, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9551629","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":635461591,"identity":"9cd696a5-f1c3-4e1c-b3a4-902eaf7b6d0f","order_by":0,"name":"Marie Weinreich Petersen","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAlUlEQVRIiWNgGAWjYPACGxBhTIqOhDTStRwmQYtu+xnDx4U/zufrNjBvNiBKi9mZHGPjGQm3LbcdYCtOIE7Lgdxt0jwJtw3MDvAYHyBOy/m323/zJJwjRcuN3G3MPAkHwFqIdNiN95+lZ6QlG5gdZism0vvn0xI/F9jYGZgdb94sQZQWEGBGIknSMgpGwSgYBaMAFwAASfUt77NQTVEAAAAASUVORK5CYII=","orcid":"","institution":"Aarhus University Hospital","correspondingAuthor":true,"prefix":"","firstName":"Marie","middleName":"Weinreich","lastName":"Petersen","suffix":""},{"id":635461592,"identity":"35df803e-7721-4bd9-967e-6c6dd8be0e55","order_by":1,"name":"Tina Birgitte Wisbech Carstensen","email":"","orcid":"","institution":"Aarhus University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Tina","middleName":"Birgitte Wisbech","lastName":"Carstensen","suffix":""},{"id":635461593,"identity":"30963813-461a-484f-b7b8-f20157d429a8","order_by":2,"name":"Kaare Bro Wellnitz","email":"","orcid":"","institution":"Aarhus University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Kaare","middleName":"Bro","lastName":"Wellnitz","suffix":""},{"id":635461594,"identity":"92bca8c2-9fa2-4126-b4ea-a2a06dd127d8","order_by":3,"name":"Eva Ørnbøl","email":"","orcid":"","institution":"Aarhus University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Eva","middleName":"","lastName":"Ørnbøl","suffix":""},{"id":635461595,"identity":"d51ebc23-6870-49b2-9031-b5a44fc30bd6","order_by":4,"name":"Thomas Meinertz Dantoft","email":"","orcid":"","institution":"Bispebjerg/Frederiksberg Hospital","correspondingAuthor":false,"prefix":"","firstName":"Thomas","middleName":"Meinertz","lastName":"Dantoft","suffix":""},{"id":635461596,"identity":"da6e5085-b1e1-4d1d-83f6-de52dd1a9450","order_by":5,"name":"Lene Falgaard Eplov","email":"","orcid":"","institution":"Capital Region","correspondingAuthor":false,"prefix":"","firstName":"Lene","middleName":"Falgaard","lastName":"Eplov","suffix":""},{"id":635461597,"identity":"e7713015-fb0a-453c-8ce1-9b0425e6be2f","order_by":6,"name":"Lisbeth Frostholm","email":"","orcid":"","institution":"Aarhus University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Lisbeth","middleName":"","lastName":"Frostholm","suffix":""},{"id":635461598,"identity":"4f723fb7-8620-4f3d-8e55-d26b23fe00f0","order_by":7,"name":"Prof. Per Fink","email":"","orcid":"","institution":"Aarhus University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Prof.","middleName":"Per","lastName":"Fink","suffix":""}],"badges":[],"createdAt":"2026-04-28 09:23:34","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9551629/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9551629/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":108806528,"identity":"c9af7caa-88ad-4534-9550-a939d9d090c0","added_by":"auto","created_at":"2026-05-08 15:28:50","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":487119,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9551629/v1/fe6e3843-8b93-4d09-a6a8-1a398eb54363.pdf"},{"id":108709501,"identity":"6e5e52a9-d04d-42e4-beb3-f5345f1a2c7b","added_by":"auto","created_at":"2026-05-07 14:01:02","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":71266,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementalMaterialsBMCMedicine.docx","url":"https://assets-eu.researchsquare.com/files/rs-9551629/v1/05125af27b3e9f70fbfe5eb0.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eMental disorders as risk factors for developing functional somatic disorder - \u003cem\u003ea Danish population-based follow-up study\u003c/em\u003e\u003c/p\u003e","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eFunctional somatic disorder (FSD) is a common condition characterized by persistent physical symptoms that cannot be better explained by other psychiatric or medical condition (1). As a unifying diagnosis, FSD encompasses many functional symptomatic syndrome diagnoses such as irritable bowel syndrome, fibromyalgia/chronic widespread pain, and chronic fatigue syndrome (2, 3). FSD is prevalent in all medical settings and the diagnosis is based on medical history and a characteristic illness pattern (1). Our knowledge about the causes of FSD is still sparse, however, it is well accepted that it has a multifactorial aetiology, comprising both biological, psychological, and social factors (4).\u003c/p\u003e \u003cp\u003eResearch on patients with severe FSD has revealed high prevalence of both physical and mental comorbidities (5, 6). A retrospective analysis of primary care claims demonstrated that mental disorders were associated with an increased likelihood of receiving a functional somatic syndrome diagnosis five years subsequently (7). Additionally, a population-based study indicated that FSD is associated with self-reported physical diseases, depression, and anxiety (3). Psychopathology has been found to predict irritable bowel syndrome and fibromyalgia, somatic symptoms, and chronic fatigue syndrome (8\u0026ndash;12). However, the previous studies may carry some limitations: Clinical studies have used highly selected patient samples which may induce risk of selection bias, and most population-based studies have used self-report for establishing FSD diagnoses and mental disorder diagnoses which may inflict a risk of misclassification.\u003c/p\u003e \u003cp\u003eHence, more studies into these aspects with a sound methodology in measuring both FSD and mental disorders are needed. To address key limitations in previous research, particularly the reliance on self-reported mental health measures, the current study included data from both a baseline and follow-up measurement of a large randomly obtained Danish population cohort. Validated symptom questionnaires and diagnostic interviews were used for the establishment of FSD diagnoses. Psychiatric discharge diagnoses and prescription psychoactive medication were obtained from comprehensive Danish Central Registries in a period of 10 years before study inclusion.\u003c/p\u003e \u003cp\u003eThe objective of the current study was twofold: First, to investigate the association between mental disorders and FSD in a randomly selected population-based cohort. Second, to investigate whether mental disorders were risk factors for newly developed (incident) FSD over a 5-year period. It was hypothesized that mental disorders would be positively associated with FSD and act as risk factor for the development of incident FSD.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n \u003ch2\u003eStudy population\u003c/h2\u003e\n \u003cp\u003eData from two measurements of the Danish Study of Functional Disorders (DanFunD), a general population cohort, was included in the study (13): The baseline investigation, conducted in the years 2011\u0026ndash;2015, and the 5-year follow-up (FU) investigation, conducted in year 2018\u0026ndash;2021. Participants in the baseline investigation were randomly drawn from the Danish Civil Registration system. The exclusion criteria were: not born in Denmark, not being a Danish citizen, and pregnancy.\u003c/p\u003e\n \u003cp\u003eThe DanFunD baseline investigation comprises a total of 9,656 (33.7% of the invited participants) men and women aged 18\u0026ndash;76 years born in Denmark and living in the Western part of greater Copenhagen. All participants completed questionnaires about physical and mental health, among others. A stratified subsample (n\u0026thinsp;=\u0026thinsp;2,450) including every tenth participant and all participants with high symptom scores on the DanFunD baseline symptom questionnaires were invited to participate in a diagnostic interview (the Research Interview for Functional somatic Disorders (RIFD)), performed by trained family physicians (14). The RIFD interview was developed from the large Schedules of Clinical Assessment in Neuropsychiatry. A total of 1,590 (64.9%) participants accepted and participated in the interview.\u003c/p\u003e\n \u003cp\u003eFor the 5-year FU investigation, 7,289 participants from the baseline cohort were invited and 5,738 (78.7%) accepted. Of them, 1,452 were invited to participate in a second RIFD interview; 1,092 (75.2%) accepted.\u003c/p\u003e\n\u003c/div\u003e\n\u003ch3\u003eMeasures\u003c/h3\u003e\n\u003cp\u003eThe primary exposure variables were mental disorders which were established in two ways:\u003c/p\u003e\n\u003cp\u003eInpatient and outpatient hospital discharge diagnoses of mental disorders were identified in the Danish National Patient Registry according to the 10th revision of the International Classification of Diseases (ICD-10) within a time frame of 10 years before DanFunD inclusion. The Danish National Patient Registry is a population-based administrative registry, which has collected data from all public Danish hospitals since 1977 with complete nationwide coverage since 1978 (15). Denmark runs a nationwide centralized register of personal information, the Civil Registration System, for which purpose every citizen is given a unique personal identification number. All public registries in Denmark, including the Danish National Patient Registry, use this unique number, which allows linkage of registers and of trial data to register data (16). The included mental discharge diagnoses were grouped in overall categories and are displayed in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e in the Supplemental Materials. In the statistical analyses, exposure variables of mental disorders constituted an overall category of mental disorder, i.e. having received at least one of the diagnoses.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eDescriptives of the complete study sample (n\u0026thinsp;=\u0026thinsp;9,656) at baseline\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"8\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\n \u003cp\u003eWomen; N (%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003eNo FSD\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;7,325)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003eOverall FSD\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;1,543)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eSingle-organ FSD\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;1,447)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003eMulti-organ FSD\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;96)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c6\"\u003e\n \u003cp\u003eIB\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;337)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c7\"\u003e\n \u003cp\u003eCWP\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;442)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c8\"\u003e\n \u003cp\u003eCF\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;823)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e3,666 (50.05)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e1,041 (67.47)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e967 (66.83)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003e74 (77.08)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c6\"\u003e\n \u003cp\u003e252 (74.78)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c7\"\u003e\n \u003cp\u003e342 (77.38)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c8\"\u003e\n \u003cp\u003e576 (69.99)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eAge at baseline; median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e54 (44\u0026ndash;64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e55 (46\u0026ndash;63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e55 (47\u0026ndash;63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003e51 (42\u0026ndash;58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e\n \u003cp\u003e50 (40\u0026ndash;60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c7\"\u003e\n \u003cp\u003e58 (50\u0026ndash;65)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c8\"\u003e\n \u003cp\u003e50 (40\u0026ndash;59)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eSocial status; median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e7 (6\u0026ndash;8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e6 (5\u0026ndash;7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e6 (5\u0026ndash;7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003e6 (5\u0026ndash;7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e\n \u003cp\u003e6 (5\u0026ndash;7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c7\"\u003e\n \u003cp\u003e6 (5\u0026ndash;7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c8\"\u003e\n \u003cp\u003e6 (5\u0026ndash;7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003ePhysical comorbidity; N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e384 (5.24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e150 (9.72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e138 (9.54)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003e12 (12.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e\n \u003cp\u003e24 (7.12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c7\"\u003e\n \u003cp\u003e51 (11.54)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c8\"\u003e\n \u003cp\u003e72 (8.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eNeuroticism; median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e15 (10\u0026ndash;19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e20 (15\u0026ndash;26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e20 (15\u0026ndash;26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003e26.5 (22\u0026ndash;32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e\n \u003cp\u003e22 (16\u0026ndash;27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c7\"\u003e\n \u003cp\u003e20 (15\u0026ndash;26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c8\"\u003e\n \u003cp\u003e24 (18\u0026ndash;29)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eAt least one psychiatric discharge diagnosis; N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e158 (2.16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e120 (7.78)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e98 (6.77)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003e22 (22.92)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e\n \u003cp\u003e31 (9.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c7\"\u003e\n \u003cp\u003e27 (6.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c8\"\u003e\n \u003cp\u003e80 (9.72)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eAnxiety disorder\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e25 (0.34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e27 (1.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e22 (1.52)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003e5 (5.21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e\n \u003cp\u003e8 (2.37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c7\"\u003e\n \u003cp\u003e5 (1.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c8\"\u003e\n \u003cp\u003e17 (2.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eDepression\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e48 (0.66)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e50 (3.24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e37 (2.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003e13 (13.54)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e\n \u003cp\u003e11 (3.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c7\"\u003e\n \u003cp\u003e11 (2.49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c8\"\u003e\n \u003cp\u003e37 (4.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003ePersonality disorder\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e5 (0.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e14 (0.91)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e10 (0.69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003e4 (4.17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e\n \u003cp\u003e9 (2.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c7\"\u003e\n \u003cp\u003e3 (0.68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c8\"\u003e\n \u003cp\u003e12 (1.46)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eStress-related disorder\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e77 (1.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e50 (3.24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e40 (2.76)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003e10 (10.42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e\n \u003cp\u003e15 (4.45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c7\"\u003e\n \u003cp\u003e11 (2.49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c8\"\u003e\n \u003cp\u003e32 (3.89)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eUse of prescription psychoactive medication (any); N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e782 (10.68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e549 (35.58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e485 (33.52)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003e64 (66.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e\n \u003cp\u003e112 (33.23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c7\"\u003e\n \u003cp\u003e184 (41.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c8\"\u003e\n \u003cp\u003e325 (39.49)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003ePrescription for antidepressive and/or anxiolytics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e745 (10.17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e545 (35.32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e481 (33.24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003e64 (66.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c7\"\u003e\n \u003cp\u003e184 (41.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c8\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eAt least one diagnosis or use of prescription psychoactive medication; N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e848 (11.58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e565 (36.62)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e499 (34.49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003e66 (68.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c6\"\u003e\n \u003cp\u003e119 (35.31)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c7\"\u003e\n \u003cp\u003e185 (41.86)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c8\"\u003e\n \u003cp\u003e342 (41.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eAbbreviations: FSD = functional somatic disorder; IB = irritable bowel; CWP = chronic widespread pain; CF = chronic fatigue;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFSD, IB, CWP, and CF are established by means of self-reported questionnaires. Psychiatric discharge diagnoses and prescription psychoactive medication are obtained from National Danish Registries within a 10 year period before baseline. NA = not applicable because number of events were 0 or adjustment was not feasible as number of cases became too low for obeying the Statistics Denmark\u0026rsquo;s requirements for statistical disclosure control in relation to personal data.\u003c/p\u003e\n\u003cp\u003ePrescriptions of psychoactive medication included prescriptions from both hospitals and primary care and were identified from the Danish National Prescription Registry (17) within a time frame of 10 years before DanFunD inclusion. The Danish National Prescription Registry receives data recorded in the electronic dispensing systems of community pharmacies. The registry contains information about each redeemed prescription, including those describing the patient, the drug dispensed, the health provider issuing the prescription and the dispensing pharmacy.\u003c/p\u003e\n\u003cp\u003eThe included prescription psychoactive medication is displayed in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e in the Supplemental Materials. In the statistical analyses, exposure variables of prescription psychoactive medication constituted an overall category of prescription psychoactive medication, i.e. having received at least one of the prescription psychoactive medications.\u003c/p\u003e\n\u003cp\u003eSecondary exposure variables constituted age, sex, subjective social status, physical comorbidities, and neuroticism. Subjective social status was measured with one item at baseline asking the participants to rate their own social status on a scale from 1 to 10, with 1 being the lowest and 10 being the highest status in society (18). Physical disease was measured in a 10-year period before a participant\u0026apos;s inclusion in DanFunD baseline and defined as having at least one of the conditions included in the updated version of the Charlson Comorbidity Index by Quan et al. (19) which is recommended for use with contemporary administrative and register-based data. Diagnoses of these conditions was identified through the Danish National Patient Registry (15). Neuroticism was measured at baseline with the Danish version of the short-form NEO Personality Inventory (NEO-PI-Rsf), which has been validated in a large sample from the Danish population and shown acceptable psychometric properties in terms of internal consistency and reliability (20). The domain for neuroticism was scored from 0 to 48, with a higher score indicating higher levels of neuroticism.\u003c/p\u003e\n\u003ch3\u003eOutcomes\u003c/h3\u003e\n\u003cp\u003eThe unifying diagnostic construct of Bodily Distress Syndrome was used for the primary operationalisation of FSD. The construct presents with four symptom clusters; cardiopulmonary, gastrointestinal, musculoskeletal, general symptoms/fatigue, and divides patients with FSD into two types: a single-organ type, i.e., individuals with symptoms from one or two of the symptom clusters, and a multi-organ type, i.e., individuals with symptoms from at least three of the four symptom clusters. In this paper, the primary definition of FSD was the Bodily Distress Syndrome diagnostic concept. Additionally, we also included definitions of the three functional somatic syndromes: irritable bowel (IB), chronic widespread pain (CWP), and chronic fatigue (CF).\u003c/p\u003e\n\u003cp\u003eThe assessment of FSD was conducted both at baseline and at the 5-year FU investigation.\u003c/p\u003e\n\u003cp\u003eCases with FSD (single- and multi-organ type) were identified by the self-reported Bodily Distress Syndrome Checklist (21), including bothersome symptoms within the last 12 months. Additionally, a stratified subsample of participants with a clinical diagnosis of FSD was identified by means of a diagnostic interview, developed to be used as a second phase tool after a respondent\u0026rsquo;s self-report in symptom questionnaires (14). The diagnostic interviews were performed by trained primary care physicians over the phone. The physicians assessed whether a specific symptom pattern was due to an FSD rather than another physical or mental condition. The diagnostic interview has shown good criterion validity for identifying individuals with FSD (14).\u003c/p\u003e\n\u003cp\u003eIndividuals fulfilling criteria for IB (22), CWP (23), and CF (24) were identified with self-reported validated symptom questionnaires including bothersome symptoms within the last 12 months.\u003c/p\u003e\n\u003ch3\u003eStatistical analyses\u003c/h3\u003e\n\u003cp\u003eAll analyses were performed using STATA version 18.0 (25). Descriptive statistics were shown with number and percentages for categorical variables and medians with interquartile ranges (IQR) for continuous variables due to skewness of the data.\u003c/p\u003e\n\u003cp\u003eFor testing of the hypothesis that mental disorders were associated with having FSD at baseline, three sets of logistic regression models were conducted for each FSD definition. For all three sets of analyses, FSD case status at baseline was the outcome variable and separate analyses were conducted for FSD established with self-reported questionnaires and FSD diagnosed with diagnostic interviews: 1\u0026thinsp;=\u0026thinsp;FSD present, 0\u0026thinsp;=\u0026thinsp;FSD not present (controls). For the three different sets of analyses, three different variables for mental disorders received within a period of 10 years before baseline constituted the exposure variable: In the first set of analyses, the exposure variable constituted register-based overall psychiatric discharge diagnoses (at least one: yes\u0026thinsp;=\u0026thinsp;1, no\u0026thinsp;=\u0026thinsp;0); in the second set of analyses, the exposure variable constituted prescription psychoactive medicine (at least one: yes\u0026thinsp;=\u0026thinsp;1, no\u0026thinsp;=\u0026thinsp;0); and in the third set of analyses, the exposure variable constituted overall psychiatric discharge diagnoses and/or prescription psychoactive medicine (at least one: yes\u0026thinsp;=\u0026thinsp;1, no\u0026thinsp;=\u0026thinsp;0). Prevalence odds ratios (PORs) with 95% confidence intervals (CIs) were used as measure of associations. A POR\u0026thinsp;\u0026gt;\u0026thinsp;1 supported an association in the expected direction.\u003c/p\u003e\n\u003cp\u003eFor testing of the hypothesis that mental disorders were risk factors for having developed incident FSD at FU, three sets of logistic regression models were conducted in the same manner as for the above analyses. In these analyses, incident FSD at follow-up, i.e. no FSD at baseline, was the outcome variable. Separate analyses were conducted for incident FSD established with self-reported questionnaires and incident FSD diagnosed with diagnostic interviews: 1\u0026thinsp;=\u0026thinsp;FSD present, 0\u0026thinsp;=\u0026thinsp;FSD not present (controls). Odds ratios (ORs) with 95% CI were used as measure of association. An OR\u0026thinsp;\u0026gt;\u0026thinsp;1 supported an association in the expected direction.\u003c/p\u003e\n\u003cp\u003ePotential confounders were identified using directed acyclic graphs (DAGs) constructed in the browser-based programme DAGitty Version 3.0 (26). Two models were constructed: The first controlled for baseline levels of sex, age, social status, and physical comorbidity. The second additionally controlled for baseline neuroticism to assess how important a confounder this was. Linearity of age, social status, and neuroticism was visually checked by expanding the model with each independent variable introduced as natural cubic splines with five knots at the 5th, 27.5th, 50th, 72.5th, and 95th percentiles. In all models, assumption of linearity was deemed acceptable, hence, and age, social status, and neuroticism were included as linear variables in all analyses.\u003c/p\u003e\n\u003cp\u003eIn addition to unstratified analyses, sex and age stratified analyses were conducted using the same modelling procedure.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003eThe baseline sample comprised 9,656 participants (53.88% women) with a median age at baseline of 54 (IQR: 44\u0026ndash;64) years. Median social status was 7 (IQR: 6\u0026ndash;8), 584 (6.05%) had a physical condition, and the median level of neuroticism was 16 (IQR: 11\u0026ndash;21). The proportion of study participants who had received a psychiatric diagnosis at discharge from a psychiatric department within the last 10 years before baseline was 326 (3.38%) while 1,526 (15.80%) had prescribed psychoactive medication. Compared to controls, a larger fraction of participants with FSD according to the questionnaires had received a diagnosis of a mental disorder (7.8% vs 2.16%) or been prescribed psychoactive medication (35.6% vs 10.7 (Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\n \u003cp\u003eAlso, compared to controls, a larger fraction of participants with overall FSD, diagnosed with the interview, had received a diagnosis of a mental disorder (11.4% vs 4.1%) or been prescribed psychoactive medication (40.8% vs 20.7% (Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eDescriptives of the interviewed study sample (n\u0026thinsp;=\u0026thinsp;1,590) at baseline\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"5\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\n \u003cp\u003eWomen; N (%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003eNo FSD\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;1,159)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003eOverall FSD\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;412)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eSingle-organ FSD\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;326)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003eMulti-organ FSD\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;86)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e633 (54.62)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e299 (72.57)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e228 (69.94)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003e71 (82.56)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eAge at baseline; median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e55 (45\u0026ndash;64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e51 (42\u0026ndash;59)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e51 (42\u0026ndash;60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003e48.5 (39.5\u0026ndash;57)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eSocial status; median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e7 (6\u0026ndash;8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e6 (5\u0026ndash;7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e6 (5\u0026ndash;7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003e6 (5\u0026ndash;7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003ePhysical comorbidity; N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e110 (9.49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e24 (5.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e20 (6.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003e4 (4.65)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eNeuroticism; median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e16 (11\u0026ndash;22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e23.5 (17\u0026ndash;29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e23 (16\u0026ndash;28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003e26 (18\u0026ndash;32)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eAt least one psychiatric diagnosis; N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e47 (4.06)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e47 (11.41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e35 (10.74)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003e12 (13.95)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eAnxiety disorder\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e11 (0.95)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e15 (3.64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e10 (3.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003e5 (5.81)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eDepression\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e19 (1.64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e23 (5.58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e17 (5.21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003e6 (6.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003ePersonality disorder\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e6 (0.52)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e7 (1.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e4 (1.23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003e3 (3.49)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eStress-related disorder\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e20 (1.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e15 (3.64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e10 (3.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003e5 (5.81)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eUse of prescription psychoactive medication (any); N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e240 (20.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e168 (40.78)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e127 (38.96)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003e41 (47.x)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003ePrescription for antidepressive and/or anxiolytics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e235 (20.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003e41 (47.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eAt least one diagnosis or use of prescription psychoactive medication; N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e248 (21.40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e173 (41.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e130 (39.88)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\"\u003e\n \u003cp\u003e43 (50.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\"\u003eAbbreviations: FSD\u0026thinsp;=\u0026thinsp;functional somatic disorder.\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\"\u003eFSD is diagnosed with diagnostic interviews performed by trained family physicians. Psychiatric discharge diagnoses and prescription psychoactive medication are obtained from National Danish Registries within a 10 year period before baseline. NA\u0026thinsp;=\u0026thinsp;not applicable because number of events were 0 or adjustment was not feasible as number of cases became too low for obeying the Statistics Denmark\u0026rsquo;s requirements for statistical disclosure control in relation to personal data.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cp\u003eThe FU sample comprised 5,738 participants (53.33% women) with a median age of 55 (IQR: 47\u0026ndash;64). Median social status was 7 (IQR: 6\u0026ndash;8), 329 (5.73%) had a physical condition, and the median level of neuroticism was 15 (IQR: 11\u0026ndash;20). The proportion of study participants who had received a psychiatric diagnosis at discharge from a psychiatric department within the last 10 years before baseline was 149 (2.60%) while 775 (13.51%) had prescribed psychoactive medication. More detailed information about the FU samples is displayed in the Supplemental Materials, Tables S2-S3.\u003c/p\u003e\n\u003cp\u003eTable \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e presents the associations between mental disorders and FSD at baseline. For most cases, strong associations emerged with having received a psychiatric diagnosis or a prescription for psychiatric medication within a time period of 10 years before baseline. However, associations with having received at psychiatric diagnosis became insignificant for questionnaire-based IB, CWP, and CF in model 2 with additional adjustment for neuroticism. The same was the case for interview-diagnosed FSD.\u003c/p\u003e\n\u003cp\u003eNotably, in the fully adjusted model, the odds of having multi-organ FSD defined by questionnaires were significantly elevated for individuals having received a psychiatric diagnosis (POR\u0026thinsp;=\u0026thinsp;2.91, 95% CI: 1.60\u0026ndash;5.31) or prescription for psychiatric medication (POR\u0026thinsp;=\u0026thinsp;6.08, 95% CI: 3.78\u0026ndash;9.78).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eAssociation between mental disorders and use of prescription medicine and functional somatic disorder at baseline\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"4\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003eAt least one diagnosis \u003cem\u003eor\u003c/em\u003e use of prescription psychoactive medication\u003c/p\u003e\n \u003cp\u003ePOR (95% CI)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003eAt least one psychiatric diagnosis\u003c/p\u003e\n \u003cp\u003ePOR (95% CI)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eUse of prescription psychoactive medication (any)\u003c/p\u003e\n \u003cp\u003ePOR (95% CI)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e\n \u003cp\u003eCases established by self-reported symptom questionnaires at baseline\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eOverall FSD\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;1,543) \u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e\u003cstrong\u003e3.36 (2.96\u0026ndash;3.82)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e\u003cstrong\u003e2.69 (2.10\u0026ndash;3.45)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e\u003cstrong\u003e3.50 (3.08\u0026ndash;3.98)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eOverall FSD\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;1,543) \u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e\u003cstrong\u003e2.54 (2.22\u0026ndash;2.90)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.78 (1.36\u0026ndash;2.32)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e\u003cstrong\u003e2.64 (2.30\u0026ndash;3.02)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eSingle-organ FSD\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;1,447) \u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e\u003cstrong\u003e3.10 (2.72\u0026ndash;3.53)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e\u003cstrong\u003e2.38 (1.83\u0026ndash;3.10)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e\u003cstrong\u003e3.23 (2.83\u0026ndash;3.69)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eSingle-organ FSD\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;1,447) \u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e\u003cstrong\u003e2.39 (2.09\u0026ndash;2.75)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.64 (1.24\u0026ndash;2.17)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e\u003cstrong\u003e2.49 (2.16\u0026ndash;2.86)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eMulti-organ FSD\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;96) \u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e\u003cstrong\u003e11.52 (7.36\u0026ndash;18.03)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e\u003cstrong\u003e6.66 (3.87\u0026ndash;11.47)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e\u003cstrong\u003e11.67 (7.48\u0026ndash;18.19)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eMulti-organ FSD\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;96) \u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e\u003cstrong\u003e6.07 (3.76\u0026ndash;9.81)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e\u003cstrong\u003e2.91 (1.60\u0026ndash;5.31)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e\u003cstrong\u003e6.08 (3.78\u0026ndash;9.78)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eIB\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;337) \u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e\u003cstrong\u003e3.14 (2.47\u0026ndash;3.99)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e\u003cstrong\u003e2.70 (1.78\u0026ndash;4.08)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e\u003cstrong\u003e3.18 (2.49\u0026ndash;4.06)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eIB\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;337) \u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e\u003cstrong\u003e2.10 (1.62\u0026ndash;2.72)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e1.53 (0.98\u0026ndash;2.38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e\u003cstrong\u003e2.10 (1.61\u0026ndash;2.73)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eCWP\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;442) \u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e\u003cstrong\u003e3.70 (3.00-4.56)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.96 (1.26\u0026ndash;3.06)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e\u003cstrong\u003e3.90 (3.16\u0026ndash;4.80)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eCWP\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;442) \u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e\u003cstrong\u003e2.90 (2.33\u0026ndash;3.61)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e1.20 (0.75\u0026ndash;1.92)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e\u003cstrong\u003e3.05 (2.44\u0026ndash;3.80)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eCF\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;823) \u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e\u003cstrong\u003e4.06 (3.46\u0026ndash;4.77)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e\u003cstrong\u003e2.69 (2.01\u0026ndash;3.59)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e\u003cstrong\u003e4.18 (3.55\u0026ndash;4.93)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eCF\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;823) \u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e\u003cstrong\u003e2.48 (2.08\u0026ndash;2.95)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e1.27 (0.92\u0026ndash;1.76)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e\u003cstrong\u003e2.53 (2.11\u0026ndash;3.02)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e\n \u003cp\u003eCases established with diagnostic interviews at baseline\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eOverall FSD\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;412)\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e\u003cstrong\u003e2.45 (1.89\u0026ndash;3.17)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e\u003cstrong\u003e2.14 (1.36\u0026ndash;3.37)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e\u003cstrong\u003e2.49 (1.91\u0026ndash;3.24)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eOverall FSD\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;412) \u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.81 (1.37\u0026ndash;2.39)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e1.39 (0.86\u0026ndash;2.24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.84 (1.39\u0026ndash;2.44)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eSingle-organ FSD\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;326)\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e\u003cstrong\u003e2.29 (1.73\u0026ndash;3.03)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e\u003cstrong\u003e2.15 (1.32\u0026ndash;3.49)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e\u003cstrong\u003e2.34 (1.76\u0026ndash;3.11)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eSingle-organ FSD\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;326) \u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.75 (1.30\u0026ndash;2.36)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e1.48 (0.89\u0026ndash;2.45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.79 (1.32\u0026ndash;2.42)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eMulti-organ FSD\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;86)\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e\u003cstrong\u003e3.24 (2.00-5.25)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e\u003cstrong\u003e2.22 (1.03\u0026ndash;4.78)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e\u003cstrong\u003e3.18 (1.96\u0026ndash;5.17)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eMulti-organ FSD\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;86) \u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e\u003cstrong\u003e2.00 (1.18\u0026ndash;3.39)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e1.18 (0.52\u0026ndash;2.69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.97 (1.17\u0026ndash;3.35)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\"\u003eLogistic regression analyses: \u003csup\u003e1\u003c/sup\u003eadjusted for baseline levels of age, sex, social status, and physical comorbidity; \u003csup\u003e2\u003c/sup\u003eadditional adjustment for baseline levels of neuroticism.\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\"\u003eAbbreviations: FSD\u0026thinsp;=\u0026thinsp;functional somatic disorder; IB\u0026thinsp;=\u0026thinsp;irritable bowel; CWP\u0026thinsp;=\u0026thinsp;chronic widespread pain; CF\u0026thinsp;=\u0026thinsp;chronic fatigue; POR\u0026thinsp;=\u0026thinsp;prevalence odds ratio; CI\u0026thinsp;=\u0026thinsp;confidence interval\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eSex-stratified analyses of the association between mental disorders and questionnaire-based FSD at baseline showed no substantial differences between men and women. However, no associations were observed in men between interview-diagnosed FSD and mental disorder (Table S4). Age-stratified analyses similarly showed no major differences across age groups; however, for interview-diagnosed FSD, associations were generally not significant in the youngest age group (18\u0026ndash;39 years) (Table S5).\u003c/p\u003e\n\u003cp\u003eTable \u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e outlines the associations between mental disorders and incident FSD at follow-up. For questionnaire-based incident cases of FSD, strong associations were found besides from the multi-organ FSD type. The absence of a significant association for multi-organ FSD may, however, be attributed to the small number of cases (n\u0026thinsp;=\u0026thinsp;29) which also made adjustment for neuroticism in model 2 not feasible. Strong associations were found for CWP and CF in most cases. However, for IB, no significant associations were found.\u003c/p\u003e\n\u003cp\u003eFor cases of newly developed FSD established by diagnostic interviews, associations were found between having received prescriptions for psychiatric medication and overall FSD in model 1 (OR\u0026thinsp;=\u0026thinsp;2.22, 95% CI: 1.12\u0026ndash;4.42). Also, associations were found between multi-organ FSD and having received a psychiatric diagnosis \u003cem\u003eor\u003c/em\u003e a prescription for psychiatric medication (OR\u0026thinsp;=\u0026thinsp;4.38, 95% CI: 1.15\u0026ndash;16.67). However, analyses on interview-established multi-organ FSD were not adjusted owing to insufficient case numbers (n\u0026thinsp;=\u0026thinsp;9).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eMental disorders as risk factor for developing functional somatic disorder at follow-up\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"4\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003eAt least one diagnosis \u003cem\u003eor\u003c/em\u003e use of prescription psychoactive medication\u003c/p\u003e\n \u003cp\u003eOR (95% CI)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003eAt least one psychiatric diagnosis\u003c/p\u003e\n \u003cp\u003eOR (95% CI)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eUse of prescription psychoactive medication (any)\u003c/p\u003e\n \u003cp\u003eOR (95% CI)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e\n \u003cp\u003eIncident cases established by self-reported symptom questionnaires at follow-up\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eOverall FSD\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;548) \u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.95 (1.53\u0026ndash;2.47)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e\u003cstrong\u003e2.54 (1.56\u0026ndash;4.12)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.97 (1.54\u0026ndash;2.52)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eOverall FSD\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;548) \u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.60 (1.24\u0026ndash;2.05)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.90 (1.15\u0026ndash;3.14)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.60 (1.24\u0026ndash;2.07)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eSingle-organ FSD\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;519) \u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.98 (1.56\u0026ndash;2.53)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e\u003cstrong\u003e2.69 (1.65\u0026ndash;4.36)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e\u003cstrong\u003e2.00 (1.56\u0026ndash;2.57)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eSingle-organ FSD\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;519) \u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.68 (1.31\u0026ndash;2.17)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e\u003cstrong\u003e2.07 (1.25\u0026ndash;3.41)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.69 (1.30\u0026ndash;2.19)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eMulti-organ FSD\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;29) \u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e1.85 (0.70\u0026ndash;4.88)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e2.02 (0.76\u0026ndash;5.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eMulti-organ FSD\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;29) \u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eIB\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;105) \u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e1.46 (0.86\u0026ndash;2.48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e1.24 (0.44\u0026ndash;3.54)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e1.38 (0.79\u0026ndash;2.40)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eIB\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;105) \u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e1.22 (0.70\u0026ndash;2.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e0.91 (0.31\u0026ndash;2.68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e1.13 (0.63\u0026ndash;2.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eCWP\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;190) \u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e\u003cstrong\u003e2.02 (1.40\u0026ndash;2.91)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e\u003cstrong\u003e2.15 (1.01\u0026ndash;4.59)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.98 (1.37\u0026ndash;2.87)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eCWP\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;190) \u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.89 (1.30\u0026ndash;2.76)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e1.80 (0.83\u0026ndash;3.92)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.85 (1.26\u0026ndash;2.72)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eCF\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;257) \u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e\u003cstrong\u003e2.52 (1.86\u0026ndash;3.43)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e\u003cstrong\u003e2.23 (1.25\u0026ndash;3.97)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e\u003cstrong\u003e2.49 (1.81\u0026ndash;3.43)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eCF\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;257) \u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.80 (1.30\u0026ndash;2.50)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e1.36 (0.74\u0026ndash;2.51)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.74 (1.24\u0026ndash;2.44)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e\n \u003cp\u003eIncident cases established with diagnostic interviews at follow-up\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eOverall FSD\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;59) \u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e1.87 (0.95\u0026ndash;3.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e1.81 (0.52\u0026ndash;6.27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e\u003cstrong\u003e2.22 (1.12\u0026ndash;4.42)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eOverall FSD\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;59) \u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e1.14 (0.54\u0026ndash;2.41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e1.01 (0.27\u0026ndash;3.76)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e1.39 (0.66\u0026ndash;2.93)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eSingle-organ FSD\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;50) \u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e1.48 (0.69\u0026ndash;3.18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e1.39 (0.34\u0026ndash;5.66)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003e1.79 (0.83\u0026ndash;3.88)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eSingle-organ FSD\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;50) \u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eMulti-organ FSD\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;9) \u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e\u003cstrong\u003e4.38 (1.15\u0026ndash;16.67)*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eMulti-organ FSD\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;9) \u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\"\u003eLogistic regression analyses: \u003csup\u003e1\u003c/sup\u003e adjusted for baseline levels of age, sex, social status, and physical comorbidity; \u003csup\u003e2\u003c/sup\u003eadditional adjustment for baseline levels of neuroticism.\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\"\u003e* Not adjusted due to the low number of cases, in order to avoid overfitting.\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\"\u003eAbbreviations: FSD\u0026thinsp;=\u0026thinsp;functional somatic disorder; IB\u0026thinsp;=\u0026thinsp;irritable bowel; CWP\u0026thinsp;=\u0026thinsp;chronic widespread pain; CF\u0026thinsp;=\u0026thinsp;chronic fatigue; OR\u0026thinsp;=\u0026thinsp;odds ratio; CI\u0026thinsp;=\u0026thinsp;confidence interval;. NA\u0026thinsp;=\u0026thinsp;not applicable because number of events were 0 or adjustment was not feasible as number of cases became too low for obeying the Statistics Denmark\u0026rsquo;s requirements for statistical disclosure control in relation to personal data.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\n \u003cp\u003eSex-stratified analyses of the association between mental disorders and incident FSD at follow-up indicated generally weaker associations in men than in women (Table S6). Age-stratified analyses showed no consistent pattern of associations across age groups for either questionnaire-based or interview-diagnosed cases (Table S7).\u003c/p\u003e\n\u003c/div\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eIn this prospective population-based follow-up study using historical prospective collected exposure data, we found strong associations between mental disorders and most cases of FSD, including IB, CWP, and CF. Mental disorders were identified as a significant risk factor for developing these conditions over a 5-year follow-up period, however, when adjusting for neuroticism, some of these associations attenuated. Importantly, our study design allowed for a robust investigation of these associations by combining multiple data sources, including Danish health registers and diagnostic interviews on FSD. These results are in line with studies in clinical setting and advance previous population-based studies pointing to psychopathology being a predictor for self-reported irritable bowel syndrome and fibromyalgia, somatic symptoms, and chronic fatigue syndrome (6\u0026ndash;12).\u003c/p\u003e \u003cp\u003eMore research is needed to fully understand the association between FSD and mental disorders, but it is widely held that the aetiologies for both are multifactorial, and the conditions thus may share common mechanisms including genetic dispositions (27, 28). Both bodily distress, depressed mood and anxiety are common reaction to stress, distressing feelings, thoughts etc. Despite individuals may be prone to one type of reaction, responses is often mixed and may vary over time, which might facilitate the association. Heightened attention to bodily sensations, somatosensory amplification, and negative cognitive appraisal are suggested in both anxiety and depressive disorders as well as in FSD; it has been shown that neuroticism is a risk factor for both FSD and mental disorders (29, 30). FSD may also be a reaction to bodily stress, i.e. after severe infections, physical trauma, or surgery. This may be mediated through immune activation, and immune dysregulation which has also been implicated in mental disorders (31, 32). Altered autonomic regulation and neurohormonal activity have been reported in both FSD and mental disorders, why these physiological mechanisms may be a common denominator (33, 34). Early-life adversity, psychological trauma, and chronic stress are also established risk factors for both FSD and common mental disorders (35, 36).\u003c/p\u003e \u003cp\u003eThe high comorbidity between FSD and mental disorders and the increased risk of developing FSD when having a mental disorder may have important clinical implications: First, it challenges the \u0026ldquo;either\u0026ndash;or\u0026rdquo; thinking which is often met in clinical practice and research, conceptualising FSD and functional somatic syndromes as purely a somatic condition. Second, the results suggest that timely and effective identification and treatment of mental disorders may play a preventive role in reducing the onset or severity of FSD. This underlines the importance of routine examination for anxiety, depression, and other mental disorders in patients with FSD. Strengthening diagnostics in primary care and non-psychiatric settings may therefore improve patient trajectories by ensuring that relevant psychiatric comorbidities are detected early and addressed systematically. Third, this study underlines the importance of psychiatric and psychological expertise presented in specialised FSD settings and supports close cooperation with general psychiatry. Finally, recognising mental disorders as risk factors for FSD may inform prevention strategies. Taken together, these clinical implications suggest that acknowledging the role of mental disorders in the development of FSD may lead to more accurate diagnosis, better prevention, more comprehensive treatment, and ultimately more compassionate and patient-centered care. While the hypothesis that psychopathology is a risk factor for developing FSD seems evident, some studies also point to a bidirectional relationship between psychopathology and functional gastrointestinal disorders and fibromyalgia, respectively (37, 38). To investigate if psychopathology is a consequence of FSD require a setup with a long time frame of prospective data on psychiatric discharge diagnoses and psychoactive medication to ensure that the FSD was present at first. It was therefore not feasible to make these conclusions on the basis of the current study. However, mental disorders and FSD are likely to be linked through bidirectional causal pathways. Further studies are therefore needed to establish this finding.\u003c/p\u003e \u003cp\u003eThe response rates of 29.5% for the baseline cohort and 78.7% for the 5-year follow-up investigation may have induced a risk of selection bias. For the baseline investigation, a non-responder analysis has shown that selection bias did not seem to noticeably influence the social parameters (39). However, the non-responder analysis for the 5-year FU investigation from the current study showed that the non-responders had a higher proportion of FSD than responders. This selection bias could potentially bias the obtained results towards an underestimation of the associations to mental disorders. Most recent data for the present study are on average at least six years old. Changes in mental health service use, treatment patterns, or diagnostic practice since that time may limit the contemporaneous relevance of absolute estimates, although the relative associations reported are likely to be robust to such temporal shifts. Registry diagnoses and prescription data reduce recall bias but may overlook subtle or dynamic mental-health and somatic symptom presentations.\u003c/p\u003e \u003cp\u003eFSD were defined according to a common classification framework of single- and multi-organ types, encompassing chronic widespread pain, irritable bowel, and chronic fatigue. Analyses considered both overall FSD (single- and multi-organ) and specific somatic syndromes to explore potential differences. The distinction between single- and multi-organ FSD is clinically relevant, reflecting variation in symptom distribution and complexity, and allows assessment of whether mental disorders act as a general risk factor across the FSD spectrum.\u003c/p\u003e \u003cp\u003eAlthough analyses of specific psychiatric diagnoses would be informative, limited event numbers in this population-based sample restricted statistical power. Therefore, mental disorders were analyzed as a combined category, with distributions of some specific diagnoses provided only descriptively.\u003c/p\u003e \u003cp\u003eLogistic regression was used because the timing of incident FSD could not be determined with sufficient precision. FSD was assessed at follow-up based on symptoms reported for the preceding 12 months, meaning onset could have occurred at any point during this period. This results in substantial uncertainty and interval censoring of the outcome, making time-to-event analyses such as Cox regression difficult to interpret. Assigning arbitrary event times would risk misclassification without improving inference; therefore, logistic regression was considered more appropriate.\u003c/p\u003e \u003cp\u003eThe number of incident cases was low for some of the FSD categories, especially for the multi-organ type. It was therefore not possible to adjust for relevant confounders in these cases. In order to emphasise the results from the current study, similar analyses adjusted for confounding may preferably be replicated in future studies with a larger data material.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eMental disorders are strongly associated with FSD, IB, CWP, and CF, and they may be risk factors for developing these conditions. Recognising the close association between mental disorders and FSD may have important clinical implications such as more accurate diagnosis, better prevention, and more effective treatment.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eEthical statement\u003c/h2\u003e \u003cp\u003e The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committees on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008. All procedures were approved by the Ethical Committee of the Capital Region (H-3-2011-081, H-3-2012-015), and all participants gave written informed consent.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eConsent for publication\u003c/h2\u003e \u003cp\u003eNot applicable.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eCompeting interests\u003c/h2\u003e \u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThis work was supported by grants from the Lundbeck Foundation [grant number R155-2013-14070] and the TrygFonden [grant numbers 7-11-0213 and 153171). The funding sources had no involvement in the study design; in the collection, analysis, and interpretation of data; in the writing of the paper; and in the decision to submit the paper for publication.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eMWP, KBW, TWC, E\u0026Oslash;, and PF contributed to the conception and design of the study. MWP, KBW, and E\u0026Oslash; accessed and verified the data and performed the analyses. MWP interpreted the data and drafted the article. KBW, TWC, E\u0026Oslash;, TMD, LF, LFE, and PF contributed to the interpretations of the data. All authors discussed the results and contributed to critically revising the article for important intellectual content. All authors read and approved the final version of the article.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eDuring the preparation of this work the authors used ChatGPT for some parts of the manuscript in order to improve language and readability. After using this tool, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eData collected for the study are not available because of Danish data protection regulations.Study registration: ClinicalTrials.gov: NCT06006715.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBurton C, Fink P, Henningsen P, Lowe B, Rief W. Functional somatic disorders: discussion paper for a new common classification for research and clinical use. BMC Med. 2020;18(1):34.\u003c/li\u003e\n\u003cli\u003eFink P, Schr\u0026ouml;der 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(5):415-26.\u003c/li\u003e\n\u003cli\u003ePetersen MW, Schr\u0026ouml;der A, J\u0026oslash;rgensen T, \u0026Oslash;rnb\u0026oslash;l E, Meinertz Dantoft T, Eliasen M, et al. Irritable bowel, chronic widespread pain, chronic fatigue and related syndromes are prevalent and highly overlapping in the general population: DanFunD. Scientific reports. 2020;10(1):3273-.\u003c/li\u003e\n\u003cli\u003eKleinst\u0026auml;uber M, Schr\u0026ouml;der A, Daehler S, Pallesen KJ, Rask CU, Sanyer M, et al. Aetiological Understanding of Fibromyalgia, Irritable Bowel Syndrome, Chronic Fatigue Syndrome and Classificatory Analogues: A Systematic Umbrella Review. Clinical Psychology in Europe. 2023;5(3):1-25.\u003c/li\u003e\n\u003cli\u003ePetersen MW, Skovenborg EL, Rask CU, Hoeg MD, Ornbol E, Schroder A. Physical comorbidity in patients with multiple functional somatic syndromes. A register-based case-control study. Journal of psychosomatic research. 2018;104:22-8.\u003c/li\u003e\n\u003cli\u003eSchr\u0026ouml;der A, Rehfeldt E, \u0026Oslash;rnb\u0026oslash;l E, Sharpe M, Licht RW, Fink P. Cognitive-behavioural group treatment for a range of functional somatic syndromes: randomised trial. Br J Psychiatry. 2012;200(6):499-507.\u003c/li\u003e\n\u003cli\u003eDonnachie E, Schneider A, Enck P. Comorbidities of Patients with Functional Somatic Syndromes Before, During and After First Diagnosis: A Population-based Study using Bavarian Routine Data. Sci Rep. 2020;10(1):9810.\u003c/li\u003e\n\u003cli\u003eCreed F. The risk factors for self-reported fibromyalgia with and without multiple somatic symptoms: The Lifelines cohort study. J Psychosom Res. 2022;155:110745.\u003c/li\u003e\n\u003cli\u003eCreed F. Psychiatric disorders and the onset of self-reported fibromyalgia and chronic fatigue syndrome: The lifelines cohort study. Front Psychiatry. 2023;14:1120250.\u003c/li\u003e\n\u003cli\u003eCreed F. Review article: the incidence and risk factors for irritable bowel syndrome in population-based studies. Aliment Pharmacol Ther. 2019;50(5):507-16.\u003c/li\u003e\n\u003cli\u003eCreed F. The predictors of somatic symptoms in a population sample: The Lifelines cohort study. Psychosomatic Medicine. 2022:10.1097/PSY.0000000000001101.\u003c/li\u003e\n\u003cli\u003eCreed F. Psychiatric disorders comorbid with general medical illnesses and functional somatic disorders: The Lifelines cohort study. PLoS One. 2023;18(5):e0286410.\u003c/li\u003e\n\u003cli\u003eDantoft TM, Ebstrup JF, Linneberg A, Skovbjerg S, Madsen AL, Mehlsen J, et al. Cohort description: The Danish Study of Functional Disorders. Clin Epidemiol. 2017;9:127-39.\u003c/li\u003e\n\u003cli\u003ePetersen MW, Schroder A, Jorgensen T, Ornbol E, Dantoft TM, Eliasen M, et al. RIFD - A brief clinical research interview for functional somatic disorders and health anxiety. Journal of psychosomatic research. 2019.\u003c/li\u003e\n\u003cli\u003eSchmidt M, Schmidt SA, Sandegaard JL, Ehrenstein V, Pedersen L, Sorensen HT. The Danish National Patient Registry: a review of content, data quality, and research potential. Clinical epidemiology. 2015;7:449-90.\u003c/li\u003e\n\u003cli\u003eSchmidt M, Pedersen L, Sorensen HT. The Danish Civil Registration System as a tool in epidemiology. European journal of epidemiology. 2014;29(8):541-9.\u003c/li\u003e\n\u003cli\u003ePottegard A, Schmidt SAJ, Wallach-Kildemoes H, Sorensen HT, Hallas J, Schmidt M. Data Resource Profile: The Danish National Prescription Registry. International journal of epidemiology. 2017;46(3):798-f.\u003c/li\u003e\n\u003cli\u003eSingh-Manoux A, Adler NE, Marmot MG. Subjective social status: its determinants and its association with measures of ill-health in the Whitehall II study. Soc Sci Med. 2003;56(6):1321-33.\u003c/li\u003e\n\u003cli\u003eQuan H, Li B, Couris CM, Fushimi K, Graham P, Hider P, et al. Updating and validating the Charlson comorbidity index and score for risk adjustment in hospital discharge abstracts using data from 6 countries. American Journal of Epidemiology. 2011;173(6):676-82.\u003c/li\u003e\n\u003cli\u003eCosta PJ, McCrae R. Revised NEO Personality Inventory (NEO-PI-R) and NEO Five-Factor Inventory (NEO-FFI) professional manual. Odessa, FL: Psychological Assessment Ressources. 1992.\u003c/li\u003e\n\u003cli\u003eBudtz-Lilly A, Fink P, Ornbol E, Vestergaard M, Moth G, Christensen KS, et al. A new questionnaire to identify bodily distress in primary care: The \u0026apos;BDS checklist\u0026apos;. Journal of psychosomatic research. 2015;78(6):536-45.\u003c/li\u003e\n\u003cli\u003eKay L, Jorgensen T. Redefining abdominal syndromes. Results of a population-based study. Scandinavian Journal of Gastroenterology. 1996;31(5):469-75.\u003c/li\u003e\n\u003cli\u003eWhite KP, Harth M, Speechley M, Ostbye T. Testing an instrument to screen for fibromyalgia syndrome in general population studies: the London Fibromyalgia Epidemiology Study Screening Questionnaire. The Journal of rheumatology. 1999;26(4):880-4.\u003c/li\u003e\n\u003cli\u003eChalder T, Berelowitz G, Pawlikowska T, Watts L, Wessely S, Wright D, et al. Development of a fatigue scale. Journal of psychosomatic research. 1993;37(2):147-53.\u003c/li\u003e\n\u003cli\u003eStataCorp. Stata Statistical Software: Release 18. In: College Station TSL, editor. 2023.\u003c/li\u003e\n\u003cli\u003eTextor J, van der Zander B, Gilthorpe MS, Liskiewicz M, Ellison GT. Robust causal inference using directed acyclic graphs: the R package \u0026apos;dagitty\u0026apos;. Int J Epidemiol. 2016;45(6):1887-94.\u003c/li\u003e\n\u003cli\u003eGrotzinger AD, Werme J, Peyrot WJ, Frei O, de Leeuw C, Bicks LK, et al. Mapping the genetic landscape across 14 psychiatric disorders. Nature. 2025.\u003c/li\u003e\n\u003cli\u003eKendler KS, Ohlsson H, Neale M, van Loo H, Rosmalen JGM, Sundquist J, et al. A multivariate Swedish national twin-sibling study in women of major depression, anxiety disorder, fibromyalgia, and irritable bowel syndrome. Psychol Med. 2025;55:e125.\u003c/li\u003e\n\u003cli\u003eOrmel J, Jeronimus BF, Kotov R, Riese H, Bos EH, Hankin B, et al. Neuroticism and common mental disorders: meaning and utility of a complex relationship. Clin Psychol Rev. 2013;33(5):686-97.\u003c/li\u003e\n\u003cli\u003eLamm TT, Von Schrottenberg V, Rauch A, Bach B, Pedersen HF, Rask MT, et al. Five-factor personality traits and functional somatic disorder: A systematic review and meta-analysis. Clin Psychol Rev. 2025;115:102529.\u003c/li\u003e\n\u003cli\u003eSchovsbo SU, M\u0026oslash;llehave LT, Petersen MW, Ahrendt Bjerregaard A, Eliasen M, Pedersen SB, et al. Association between infections and functional somatic disorders: a cross-sectional population-based cohort study. BMJ Open. 2022;12(11):e066037.\u003c/li\u003e\n\u003cli\u003eMousten IV, S\u0026oslash;rensen NV, Christensen RHB, Benros ME. Cerebrospinal Fluid Biomarkers in Patients With Unipolar Depression Compared With Healthy Control Individuals: A Systematic Review and Meta-analysis. JAMA Psychiatry. 2022;79(6):571-81.\u003c/li\u003e\n\u003cli\u003eGormsen L, M\u0026oslash;lgaard H, Dantoft TM, Bjerregaard AA, Fink P, Petersen MW. Autonomic arousal and heart rate variability in functional somatic disorder - a cross-sectional population-based study. Journal of Psychosomatic Research. 2025;196:112193.\u003c/li\u003e\n\u003cli\u003eVan Den Houte M, Ramakers I, Van Oudenhove L, Van den Bergh O, Bogaerts K. Comparing autonomic nervous system function in patients with functional somatic syndromes, stress-related syndromes and healthy controls. Journal of Psychosomatic Research. 2025;189:112025.\u003c/li\u003e\n\u003cli\u003ePetersen MW, Carstensen TBW, Wellnitz KB, \u0026Oslash;rnb\u0026oslash;l E, Frostholm L, Dantoft TM, et al. Neuroticism, perceived stress, adverse life events and self-efficacy as predictors of the development of functional somatic disorders: longitudinal population-based study (DanFunD). BJPsych Open. 2024;10(1):e34.\u003c/li\u003e\n\u003cli\u003eJacobsen SA, Petersen MW, Wellnitz KB, \u0026Oslash;rnb\u0026oslash;l E, Dantoft TM, J\u0026oslash;rgensen T, et al. Functional Somatic Disorders in Individuals With a History of Sexual Assault. JAMA Psychiatry. 2025.\u003c/li\u003e\n\u003cli\u003eChang MH, Hsu JW, Huang KL, Su TP, Bai YM, Li CT, et al. Bidirectional Association Between Depression and Fibromyalgia Syndrome: A Nationwide Longitudinal Study. J Pain. 2015;16(9):895-902.\u003c/li\u003e\n\u003cli\u003eKoloski NA, Jones M, Kalantar J, Weltman M, Zaguirre J, Talley NJ. The brain--gut pathway in functional gastrointestinal disorders is bidirectional: a 12-year prospective population-based study. Gut. 2012;61(9):1284-90.\u003c/li\u003e\n\u003cli\u003eSchovsbo SU, Dantoft TM, Thuesen BH, Leth-M\u0026oslash;ller KB, Eplov LF, Petersen MW, et al. Social position and functional somatic disorders: The DanFunD study. Scand J Public Health. 2021:14034948211056752.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmed","sideBox":"Learn more about [BMC Medicine](http://bmcmedicine.biomedcentral.com/)","snPcode":"12916","submissionUrl":"https://submission.nature.com/new-submission/12916/3","title":"BMC Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Functional Somatic Disorder, Irritable Bowel Syndrome, Fibromyalgia, Chronic Fatigue Syndrome, Mental Disorders, Psychiatric Diagnoses, Risk Factor, Epidemiology, Register-Based","lastPublishedDoi":"10.21203/rs.3.rs-9551629/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9551629/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eBackground\u003c/b\u003e\u003c/p\u003e \u003cp\u003eMental disorders and functional somatic disorder (FSD) often co-occur, but longitudinal population-based studies examining their temporal associations remain scarce. The objectives of this study were 1) to investigate the association between mental disorders and FSD in the baseline investigation of a randomly selected population-based cohort, and 2) to investigate whether mental disorders were risk factors for newly developed (incident) FSD over a 5-year period.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThe DanFunD baseline and 5-year follow-up (FU) investigations were used. FSD comprised the outcome variables and was established at both baseline and FU with validated symptom questionnaires and diagnostic interviews. Psychiatric discharge diagnoses and prescription psychoactive medication were exposure variables and were obtained from comprehensive Danish Central Registries in a period of 10 years before study inclusion. Prevalence odds ratios (PORs) and odds ratios (ORs) with 95% confidence intervals (CIs) were measures of association. People with lived experience of FSD were not involved in the research and writing process.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e \u003cp\u003eA total of 9,656 individuals participated in the DanFunD baseline cohort (53.9% women, median age 54 years, interquartile range (IQR): 44\u0026ndash;64 years) and 5,738 individuals participated in the 5-year FU cohort (53.3% women, median age 55 years, IQR: 47\u0026ndash;64 years). Having received a diagnosis of a mental disorder or having received prescription psychoactive medication 10 years before baseline were strongly associated with both questionnaire-based FSD (POR\u0026thinsp;=\u0026thinsp;2.54, 95% CI: 2.22\u0026ndash;2.90) and interview-diagnosed FSD (POR\u0026thinsp;=\u0026thinsp;1.81, 95% CI: 1.37\u0026ndash;2.39) at DanFunD baseline. Likewise, it was a significant risk factor for having developed FSD at FU for questionnaire-based FSD (OR\u0026thinsp;=\u0026thinsp;1.60, 95% CI: 1.24\u0026ndash;2.05). However, for interview-diagnosed FSD, a significant association could not be found (OR\u0026thinsp;=\u0026thinsp;1.14, 95% CI: 0.54\u0026ndash;2.41).\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusions\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThe study indicates that mental disorders may be risk factors for developing FSD. The findings suggest that effective management of mental disorders may help lower the risk of subsequent FSD, emphasizing the importance of accurate diagnosis and coordinated care across clinical services. They also point to preventive opportunities, where early psychological or stress-management interventions may benefit individuals at elevated risk.\u003c/p\u003e","manuscriptTitle":"Mental disorders as risk factors for developing functional somatic disorder - a Danish population-based follow-up study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-05-07 14:00:59","doi":"10.21203/rs.3.rs-9551629/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"274240284711482169849047936335411912587","date":"2026-05-14T07:35:09+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-29T12:14:51+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-29T05:15:51+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-04-29T04:35:55+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Medicine","date":"2026-04-28T09:14:20+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmed","sideBox":"Learn more about [BMC Medicine](http://bmcmedicine.biomedcentral.com/)","snPcode":"12916","submissionUrl":"https://submission.nature.com/new-submission/12916/3","title":"BMC Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"3c7a7327-d784-48c6-8a38-5dc849eae1c6","owner":[],"postedDate":"May 7th, 2026","published":true,"recentEditorialEvents":[{"type":"reviewerAgreed","content":"274240284711482169849047936335411912587","date":"2026-05-14T07:35:09+00:00","index":19,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-07T14:00:59+00:00","versionOfRecord":[],"versionCreatedAt":"2026-05-07 14:00:59","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9551629","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9551629","identity":"rs-9551629","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}