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Marie Weinreich Petersen,1,2 Tina Birgitte Wisbech Carstensen,1,2 Lisbeth Frostholm,1,2 Kaare Bro Wellnitz,1,2 Eva Ørnbøl,1,2 Torben Jørgensen,3,4 Lene Falgaard Eplov,5 Thomas Meinertz Dantoft,3 Per Fink1,2 1Research Clinic for Functional Disorders and Psychosomatics, Aarhus University Hospital, Aarhus, Denmark; 2Department of Clinical Medicine, University of Aarhus, Aarhus, Denmark; 3Center for Clinical Research and Prevention, Bispebjerg/Frederiksberg Hospital, Frederiksberg, Capital Region, Denmark; 4Department of Public Health, Faculty of Medical Sciences, Copenhagen University, Copenhagen, Denmark; 5Copenhagen Research Center for Mental Health – CORE, Mental Health Centre Copenhagen, Copenhagen, Capital Region, DenmarkCorrespondence: Marie Weinreich Petersen, Research Clinic for Functional Disorders and Psychosomatics, Aarhus University Hospital, Palle Juul-Jensens Boulevard 11, Aarhus, 8200, Denmark, Tel +45 7846 4310, Email mawept@rm.dkObjective: Several psychological factors have been proposed to be associated with functional somatic disorders (FSD) including functional somatic syndromes, such as irritable bowel, chronic widespread pain, and chronic fatigue. However, large randomly selected population-based studies of this association are sparse. This study aimed to investigate the association between FSD and perceived stress and self-efficacy, respectively, and to investigate if FSD differed from severe physical diseases on these aspects.Methods: This cross-sectional study included a random sample of the adult Danish population (n = 9656). FSD were established using self-reported questionnaires and diagnostic interviews. Perceived stress was measured with Cohen’s Perceived Stress Scale and self-efficacy with the General Self-Efficacy Scale. Data were analysed with generalized linear models and linear regression models.Results: FSD were associated with higher perceived stress and lower self-efficacy, especially for the multi-organ and the general symptoms/fatigue FSD types and for chronic fatigue. However, controlling for the personality trait neuroticism altered the associations with self-efficacy so it became insignificant. The analysis did not support an important interaction between perceived stress and self-efficacy on the likelihood of having FSD. Individuals with FSD presented levels of perceived stress that were not equal, ie higher, to those in individuals with severe physical diseases.Conclusion: FSD were positively associated with perceived stress and negatively associated with self-efficacy. Our study may point to stress being part of the symptomatology of FSD. This underlines the severity of having FSD and stresses the relevance of the resilience theory in the understanding of the condition.Keywords: functional somatic disorders, functional somatic syndromes, perceived stress, self-efficacy, irritable bowel syndrome, fibromyalgia, chronic fatigue syndrome, population-based

Line Tang Møllehave,1 Allan Linneberg,1–3 Tea Skaaby,1 Nils Knudsen,4 Torben Jørgensen,1,5,6 Betina Heinsbæk Thuesen1 1Center for Clinical Research and Disease Prevention, Bispebjerg and Frederiksberg Hospital, Capital Region, Copenhagen, Denmark; 2Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; 3Juliane Marie Centre, Rigshospitalet, Copenhagen, Denmark; 4Department of Endocrinology, Bispebjerg University Hospital, University of Copenhagen, Copenhagen, Denmark; 5Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; 6Faculty of Medicine, Aalborg University, Aalborg, Denmark Background: Long-term iodine exposure may influence the frequency of thyroid disease treatments through fluctuations in thyroid diseases. Yet, the long-term fluctuations in thyroid disease treatments upon iodine fortification (IF) are not fully known. We aimed to examine the development in thyroid disease treatments in Denmark before and following the implementation of IF in 2000. Methods: Nationwide data on antithyroid medication, thyroid hormone therapy, thyroid surgery, and radioiodine treatment were obtained from Danish registries. Negative binominal regression was applied to analyze annual changes in treatment rates adjusted for region of residence, sex, and age. Results: Incidence of antithyroid medication transiently increased but fell and reached steady state from 2010 at an incidence rate ratio (RR) of 0.72 (95% confidence interval [CI] 0.67–0.77) compared to year 2000. Thyroid hormone therapy increased and reached steady state in 2010 at an incidence RR of 1.75 (95% CI 1.62–1.89) compared to year 2000. Thyroid surgery was constant except for higher rates in 2014–2015, and radioiodine treatment fluctuated with no apparent pattern. Conclusion: Ten years after IF, a steady state was observed for incident antithyroid medication below the level at IF, and thyroid hormone therapy above the level at IF. Only small changes were observed in thyroid surgery and radioiodine treatment. In the same period, changes in diagnostic and treatment practices and lifestyle factors are likely to have occurred and should be considered when evaluating the effects of IF on treatment of thyroid diseases. Keywords: iodine, pharmacoepidemiology, thyroid diseases

Marie Eliasen,1 Torben Jørgensen,1–3 Andreas Schröder,4 Thomas Meinertz Dantoft,1 Per Fink,4 Chalotte Heinsvig Poulsen,1,5 Nanna Borup Johansen,1 Lene Falgaard Eplov,5 Sine Skovbjerg,1 Svend Kreiner2 1Research Centre for Prevention and Health, Centre for Health, The Capital Region of Denmark, Glostrup, 2Department of Public Health, University of Copenhagen, Copenhagen, 3Department of Clinical Medicine, Aalborg University, Aalborg, 4Research Clinic for Functional Disorders and Psychosomatics, Aarhus University Hospital, Aarhus C, 5Mental Health Centre Copenhagen, The Capital Region of Denmark, Hellerup, Denmark Purpose: The aim of this study was to identify and describe somatic symptom profiles in the general adult population in order to enable further epidemiological research within multiple somatic symptoms.Methods: Information on 19 self-reported common somatic symptoms was achieved from a population-based questionnaire survey of 36,163 randomly selected adults in the Capital Region of Denmark (55.4% women). The participants stated whether they had been considerably bothered by each symptom within 14 days prior to answering the questionnaire. We used latent class analysis to identify the somatic symptom profiles. The profiles were further described by their association with age, sex, chronic disease, and self-perceived health.Results: We identified 10 different somatic symptom profiles defined by number, type, and site of the symptoms. The majority of the population (74.0%) had a profile characterized by no considerable bothering symptoms, while a minor group of 3.9% had profiles defined by a high risk of multiple somatic symptoms. The remaining profiles were more likely to be characterized by a few specific symptoms. The profiles could further be described by their associations with age, sex, chronic disease, and self-perceived health.Conclusion: The identified somatic symptom profiles could be distinguished by number, type, and site of the symptoms. The profiles have the potential to be used in further epidemiological studies on risk factors and prognosis of somatic symptoms but should be confirmed in other population-based studies with specific focus on symptom burden. Keywords: epidemiology, somatic symptoms, subjective health complaints, multiple symptoms, functional somatic syndromes, health status

Chalotte Heinsvig Poulsen,1,2 Lene Falgaard Eplov,2 Carsten Hjorthøj,2 Marie Eliasen,1 Sine Skovbjerg,1 Thomas Meinertz Dantoft,1 Andreas Schröder,3 Torben Jørgensen1,4,5 1Research Centre for Prevention and Health, Capital Region of Denmark, Glostrup, 2Copenhagen University Hospital, Mental Health Centre Copenhagen, Hellerup, 3Research Clinic for Functional Disorders and Psychosomatics, Aarhus University Hospital, Aarhus, 4Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, 5The Faculty of Medicine, Aalborg University, Aalborg, Denmark Objective: Irritable bowel syndrome (IBS) is associated with mental vulnerability, and half of patients report comorbid somatic and mental symptoms. We aimed to investigate the relationship between an IBS symptom continuum and the subsequent development of common mental disorders (CMDs) and functional somatic syndromes (FSSs).Methods and study design: A longitudinal population-based study comprising two 5-year follow-up studies, Dan-MONICA 1 (1982–1987) and Inter99 (1999–2004), recruited from the western part of Copenhagen County. The total study population (n = 7,278) was divided into symptom groups according to the degree of IBS definition fulfillment at baseline and/or follow-up and was followed until December 2013 in Danish central registries. Cox regression was used for the analyses, adjusting for age, sex, length of education and cohort membership. In a subsequent analysis, we adjusted for mental vulnerability as a risk factor for both CMDs and FSSs, including IBS.Results: Over a 5-year period, 51% patients had no IBS symptoms, 17% patients had IBS symptoms without abdominal pain, 22% patients had IBS symptoms including abdominal pain and 10% patients fulfilled the IBS definition. IBS and IBS symptoms including abdominal pain were significantly associated with the development of CMDs and other FSSs identified in secondary care. When adjusting for mental vulnerability, IBS and IBS symptoms including abdominal pain were no longer associated with CMDs, but the significant relationship to other FSSs remained.Conclusion: In a clinical setting, the perspective should be broadened to individuals not fulfilling the symptom cluster of IBS but who report frequent abdominal pain. Additionally, it is important to combine symptom-based criteria of IBS with psychosocial markers such as mental vulnerability, because it could guide clinicians in decisions regarding prognosis and treatment. Keywords: functional gastrointestinal symptoms, abdominal pain, comorbidity, somatization, neuroticism

Thomas Meinertz Dantoft,1 Jeanette Frost Ebstrup,1 Allan Linneberg,1–3 Sine Skovbjerg,1 Anja Lykke Madsen,1 Jesper Mehlsen,4 Louise Brinth,4 Lene Falgaard Eplov,5 Tina Wisbech Carstensen,6,7 Andreas Schroder,6,7 Per Klausen Fink,6,7 Erik Lykke Mortensen,8 Torben Hansen,9 Oluf Pedersen,9 Torben Jørgensen1,10,11 1Research Centre for Prevention and Health, The Capital Region of Denmark, Glostrup, 2Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, 3Department of Clinical Experimental Research, Rigshospitalet, Glostrup, 4Coordinating Research Centre, Bispebjerg and Frederiksberg Hospital, Frederiksberg, 5Mental Health Centre Copenhagen, Research Unit, Mental Health Services, Capital Region of Denmark, Copenhagen, 6The Research Clinic for Functional Disorders and Psychosomatics, Aarhus University Hospital, 7Faculty of Health Sciences, University of Aarhus, Aarhus, 8Department of Public Health and Center for Healthy Aging, 9Novo Nordisk Foundation Center for Basic Metabolic Research, 10Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, 11Faculty of Medicine, Aalborg University, Aalborg, Denmark Abstract: The Danish study of Functional Disorders (DanFunD) cohort was initiated to outline the epidemiology of functional somatic syndromes (FSS) and is the first larger coordinated epidemiological study focusing exclusively on FSS. FSS are prevalent in all medical settings and can be defined as syndromes that, after appropriate medical assessment, cannot be explained in terms of a conventional medical or surgical disease. FSS are frequent and the clinical importance varies from vague symptoms to extreme disability. No well-described medical explanations exist for FSS, and how to delimit FSS remains a controversial topic. The specific aims with the cohort were to test delimitations of FSS, estimate prevalence and incidence rates, identify risk factors, delimitate the pathogenic pathways, and explore the consequences of FSS. The study population comprises a random sample of 9,656 men and women aged 18–76 years from the general population examined from 2011 to 2015. The survey comprises screening questionnaires for five types of FSS, ie, fibromyalgia, whiplash-associated disorder, multiple chemical sensitivity, irritable bowel syndrome, and chronic fatigue syndrome, and for the unifying diagnostic category of bodily distress syndrome. Additional data included a telephone-based diagnostic interview assessment for FSS, questionnaires on physical and mental health, personality traits, lifestyle, use of health care services and social factors, and a physical examination with measures of cardiorespiratory and morphological fitness, metabolic fitness, neck mobility, heart rate variability, and pain sensitivity. A biobank including serum, plasma, urine, DNA, and microbiome has been established, and central registry data from both responders and nonresponders are similarly available on morbidity, mortality, reimbursement of medicine, heath care use, and social factors. A complete 5-year follow-up is scheduled to take place from year 2017 to 2020, and further reexaminations will be planned. Several projects using the DanFunD data are ongoing, and findings will be published in the coming years. Keywords: functional somatic syndromes, medically unexplained symptoms, epidemiology, longitudinal cohort study, pathophysiology, risk factors