Factors associated with having previously received a diagnosis of fibromyalgia, chronic fatigue syndrome and irritable bowel syndrome: A cross sectional DanFunD study.

OBJECTIVES: Fibromyalgia, chronic fatigue syndrome, and irritable bowel syndrome are highly prevalent conditions and part of the functional somatic syndromes (FSS) diagnosis, that are classified under the unifying umbrella term functional somatic disorder (FSD). Multiple factors are associated with FSD symptom development; However, few studies have explored these associations in relation to the diagnosis status. This study aims to examine associations with a previously received FSS diagnosis from a physician in participants fulfilling the FSD diagnostic criteria in a population-based sample. METHODS: This research employs a comprehensive observational approach using a cross sectional design with data from the DanFunD part two cohort. Information about received FSS diagnoses was obtained from self-reported questionnaires. Participants fulfilling the FSD diagnostic criteria were identified with both self-reported questionnaires and diagnostic interviews. Validated questionnaires were used to assess the examined factors. RESULTS: 1704 cases fulfilled the diagnostic criteria for an FSD according to questionnaires or interviews in the DanFunD study. In participants fulfilling the diagnostic criteria, having previously received an FSS diagnosis by a physician was strongly associated with female sex, negative illness perceptions and poor health-related quality of life for questionnaire and interview-based diagnoses. Less consistent associations were observed for lower socioeconomic status, anxiety, and adverse life events. CONCLUSION: Previously received FSS diagnoses showed associations with multiple factors with a particular strong association with female sex and poor health related quality of life.

Is reduced heart rate variability associated with functional somatic disorders? A cross-sectional population-based study; DanFunD.

OBJECTIVES: It has been hypothesised that functional somatic disorders (FSD) could be initiated by sympathetic predominance in the autonomic nervous system as measured by low heart rate variability (HRV). Earlier studies on the association between HRV and FSD are small case-control studies hampered by selection bias and do not consider the great overlap between the various FSDs. The aim of the present study is to assess any associations between HRV and various FSDs and whether chronic stress confounds such an association. DESIGN: A cross-sectional general population-based study. SETTING: The Danish Study of Functional Somatic Disorders conducted 2013-2015 in 10 municipalities in the western part of Greater Copenhagen, Denmark. PARTICIPANTS: A total of 6891 men and women aged 18-72 years were included in the analyses after exclusion of 602 persons with missing HRV data. Various delimitations of FSD (chronic fatigue, chronic widespread pain, irritable bowel and bodily distress syndrome) were identified by validated questionnaires and diagnostic interviews. HRV parameters in time and frequency domains were calculated from successive beat-to-beat heart rate (HR) data using the 'E-motion' HR monitor device during 7 min of supine rest. Chronic stress was assessed by Cohen's self-perceived stress scale. OUTCOME MEASURES: Logistic regression analyses were used to calculate possible associations between the various delimitations of FSD and HRV adjusting for chronic stress. RESULTS: Persons with FSD had a slightly higher mean HR and lower HRV as measured by time domain parameters, whereas associations with frequency domain parameters were not consistent. Adjusting for chronic stress attenuated associations slightly. CONCLUSION: The study supports a sympathetic predominance in persons with FSD, which could not be entirely explained by chronic stress. However, it is not possible to conclude whether the association is a causal factor to or a consequence of FSD.

Neuroticism, perceived stress, adverse life events and self-efficacy as predictors of the development of functional somatic disorders: longitudinal population-based study (DanFunD).

BACKGROUND: Functional somatic disorder (FSD) is a unifying diagnosis that includes functional somatic syndromes such as irritable bowel, chronic widespread pain (CWP) and chronic fatigue. Several psychological factors are associated with FSD. However, longitudinal population-based studies elucidating the causal relationship are scarce. AIMS: To explore if neuroticism, perceived stress, adverse life events (ALEs) and self-efficacy can predict the development of FSD over a 5-year period. METHOD: A total of 4288 individuals who participated in the DanFunD baseline and 5-year follow-up investigations were included. FSD was established at both baseline and follow-up, with symptom questionnaires and diagnostic interviews. Neuroticism was measured with the short-form NEO Personality Inventory, perceived stress with the Cohen's Perceived Stress Scale, ALEs with the Danish version of the Cumulative Lifetime Adversity Measure and self-efficacy with the General Self-Efficacy Scale. Associations were investigated with multiple logistic regression models. RESULTS: Perceived stress predicted incident FSD, irritable bowel, CWP and chronic fatigue (odds ratios: 1.04-1.17). Neuroticism predicted incident FSD and chronic fatigue (odds ratios: 1.03-1.16). ALEs predicted incident FSD, CWP and chronic fatigue (odds ratios: 1.06-1.18). An increase in perceived stress from baseline to follow-up was associated with incident FSD, irritable bowel, CWP and chronic fatigue (odds ratios: 1.05-1.22). Contrary, an increase in self-efficacy seemed to be a protective factor (odds ratios: 0.89-0.99). CONCLUSIONS: High neuroticism, high perceived stress and a high number of ALEs are risk factors for the development of FSD. Particularly perceived stress seems to be an important contributor to the onset of FSD.

Lipid metabolism and functional somatic disorders in the general population. The DanFunD study.

OBJECTIVES: Earlier studies on the association between plasma lipid profiles and functional somatic disorders (FSD) are mainly small case control studies hampered by selection bias and do not consider the great overlap between the various FSDs. The aim of the present study was to investigate the associations between various FSDs and plasma lipid profiles (total cholesterol, HDL cholesterol, non-HDL cholesterol and triglycerides) in a large, unselected population. DESIGN: A cross-sectional general population-based study. SETTING: The Danish Study of Functional Somatic Disorders (DanFunD) conducted in 2011-2015 in 10 municipalities in the western part of greater Copenhagen, Denmark. PARTICIPANTS: A total of 8,608 men and women aged 18-76 years were included in the analyses. Various delimitations of FSD such as chronic fatigue, chronic widespread pain, irritable bowel, and bodily distress syndrome were measured using validated self-administrated questionnaires. Lipid parameters were measured from fasting plasma samples using colorimetric slide methods with Vitros 4600/5600 Ortho Clinical Diagnostics. OUTCOME MEASURES: Logistic regression analyses were used to calculate possible associations between plasma lipids and the various delimitations of FSD. Associations are presented by OR (95% CI) and shown in boxplots. RESULTS: We found a positive association between bodily distress syndrome and triglycerides and non-HDL cholesterol and a negative association with HDL-cholesterol, but no consistent association with total cholesterol. A similar pattern was observed for persons with chronic fatigue, and to some degree for persons with chronic widespread pain, whereas persons with irritable bowel did not show a clear association with the lipid profiles. CONCLUSION: This is the first major study on plasma lipid profiles and FSD indicating an association between some delimitations of FSD and an unfavorable lipid profile. Due to the cross-sectional design, it cannot be determined whether the findings are consequences or determinants of FSD. Further studies-preferable prospective studies-are needed.

Genome-wide association study of preserved ratio impaired spirometry (PRISm).

BACKGROUND: Preserved ratio impaired spirometry (PRISm) is defined as a forced expiratory volume in 1 s (FEV1) <80% predicted and FEV1/forced vital capacity ≥0.70. PRISm is associated with respiratory symptoms and comorbidities. Our objective was to discover novel genetic signals for PRISm and see if they provide insight into the pathogenesis of PRISm and associated comorbidities. METHODS: We undertook a genome-wide association study (GWAS) of PRISm in UK Biobank participants (Stage 1), and selected single nucleotide polymorphisms (SNPs) reaching genome-wide significance for replication in 13 cohorts (Stage 2). A combined meta-analysis of Stage 1 and Stage 2 was done to determine top SNPs. We used cross-trait linkage disequilibrium score regression to estimate genome-wide genetic correlation between PRISm and pulmonary and extrapulmonary traits. Phenome-wide association studies of top SNPs were performed. RESULTS: 22 signals reached significance in the joint meta-analysis, including four signals novel for lung function. A strong genome-wide genetic correlation (rg) between PRISm and spirometric COPD (rg=0.62, p<0.001) was observed, and genetic correlation with type 2 diabetes (rg=0.12, p=0.007). Phenome-wide association studies showed that 18 of 22 signals were associated with diabetic traits and seven with blood pressure traits. CONCLUSION: This is the first GWAS to successfully identify SNPs associated with PRISm. Four of the signals, rs7652391 (nearest gene MECOM), rs9431040 (HLX), rs62018863 (TMEM114) and rs185937162 (HLA-B), have not been described in association with lung function before, demonstrating the utility of using different lung function phenotypes in GWAS. Genetic factors associated with PRISm are strongly correlated with risk of both other lung diseases and extrapulmonary comorbidity.

Are Sexual Assaults Related to Functional Somatic Disorders? A Cross-Sectional Study.

An increasing number of sexual assaults (SAs) are being reported. This study investigated associations between SA and FSD, conceptualized as bodily distress syndrome (BDS), and five functional somatic syndromes (FSSs): chronic widespread pain (CWP), irritable bowel (IB), chronic fatigue (CF), multiple chemical sensitivity (MCS), and whiplash-associated disorder (WAD). Participants (n = 7493) from the population-based cohort Danish Study of Functional Disorders (DanFunD) completed questionnaires on FSD, emotional distress, SA, and sociodemographics. Risk ratios (RRs) for each FSD and emotional distress were calculated in nine models with SA as the primary exposure using generalized linear models with binomial family and log link and were adjusted for other potential risk factors. The results showed that SA was associated with single-organ FSD (RR = 1.51; 95% CI = 1.22-1.87), multi-organ FSD (RR = 3.51; 95% CI = 1.89-6.49), CWP (RR = 1.28; 95% CI = 0.83-1.98), IB (RR = 2.00; 95% CI = 1.30-3.07), CF (RR = 1.81; 95% CI = 1.42-2.32), WAD (RR = 2.62; 95% CI = 1.37-5.03), MCS (RR = 3.04; 95% CI = 1.79-5.17), emotional distress (RR = 1.75; 95% CI = 1.21-2.54), and health anxiety (RR = 1.65; 95% CI = 1.10-2.46). Overall, SA victims experienced significantly more somatic symptoms than individuals not exposed to SA. Adjusting for physical and emotional abuse did not change the observed associations. Our results suggest a large impact of SA on the overall somatic and mental health of SA victims. Due to the cross-sectional study design, further studies are required.

The association of vitamin K status with lung function and disease in a general population.

Introduction: Matrix Gla protein (MGP) is an inhibitor of lung tissue calcification. The plasma level of dephosphorylated-uncarboxylated MGP (dp-ucMGP) is a biomarker of vitamin K status. The present study assessed whether lower vitamin K status (reflected by higher dp-ucMGP) was associated with lung function and lung disease/symptoms. Methods: A general population sample of 4092 individuals, aged 24 to 77 years, underwent a health examination including questionnaires, spirometry and measurements of plasma dp-ucMGP. Associations of dp-ucMGP with lung function and self-reported disease/symptoms were estimated using regression models adjusted for age, sex and height. Associations were expressed as ß-estimates or odds ratios (ORs) per doubling in dp-ucMGP. Results: Lower vitamin K status (higher dp-ucMGP) was associated with lower forced expiratory volume in 1 s (FEV1) (98 mL; 95% CI: 54-141 mL) and lower forced vital capacity (FVC) (136 mL; 95% CI: 85-187 mL). Dp-ucMGP was not associated with the FEV1/FVC ratio (0.0 percentage points higher than the expected value; 95% CI: -1.0-1.0). Furthermore, lower vitamin K status was associated with COPD (OR 2.24, 95% CI: 1.53-3.27), wheezing (OR 1.81, 95% CI: 1.44-2.28) and asthma (OR 1.44, 95% CI: 1.12-1.83). Conclusion: Lower vitamin K status was associated with lower ventilatory capacity (lower FEV1 and FVC), and with higher risk of self-reported asthma, COPD and wheezing. Vitamin K status was not associated with airflow obstruction (FEV1/FVC ratio).

High Perceived Stress and Low Self-Efficacy are Associated with Functional Somatic Disorders: The DanFunD Study.

Objective: 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.

Social economic factors and the risk of multiple chemical sensitivity in a Danish population-based cross-sectional study: Danish Study of Functional Disorders (DanFunD).

OBJECTIVES: Multiple chemical sensitivity (MCS) is a rare multisystem and poly-symptomatic disease characterised by a report of various somatic symptoms attributed to inhalation of volatile chemicals in usually harmless doses. The aim was to explore four selected social factors and the risk of MCS in the general Danish population. DESIGN: A cross-sectional general population-based study. SETTING: The Danish Study of Functional Disorders was conducted from 2011 to 2015 which included 9656 participants. PARTICIPANTS: A total of 8800 participants were included in analyses after observations with missing data on exposure and/or outcome were excluded. A total of 164 cases fulfilled the questionnaire criteria for MCS. Of the 164 MCS cases, 101 reported no comorbid functional somatic disorder (FSD) and were included in a subgroup analysis. A total of 63 MCS cases fulfilled the criteria for at least one additional FSD, this subgroup was not included in further analysis. The remaining study population without MCS or any FSD were regarded as controls. OUTCOME MEASURES: We used adjusted logistic regression to calculate OR and 95% CIs of MCS and MCS without FSD comorbidities for each social variable separately including education, employment, cohabitation and subjective social status. RESULTS: We found an increased risk of MCS among the unemployed (OR: 2.95, 95% CI: 1.75 to 4.97), and a twofold increased risk of MCS among individuals with low subjective social status (OR: 2.00, 95% CI: 1.08 to 3.70). At the same time, 4 years or more of vocational training were protective of MCS. No significant associations were observed among MCS cases with no comorbid FSD. CONCLUSION: Lower socioeconomic status was found to be associated with a higher risk of having MCS but not with MCS without FSD comorbidities. Due to the cross-sectional design of the study, we cannot determine whether social status is a determinant or a consequence of MCS.

The gut microbiota in multiple sclerosis varies with disease activity.

BACKGROUND: Multiple sclerosis is a chronic immune-mediated disease of the brain and spinal cord resulting in physical and cognitive impairment in young adults. It is hypothesized that a disrupted bacterial and viral gut microbiota is a part of the pathogenesis mediating disease impact through an altered gut microbiota-brain axis. The aim of this study is to explore the characteristics of gut microbiota in multiple sclerosis and to associate it with disease variables, as the etiology of the disease remains only partially known. METHODS: Here, in a case-control setting involving 148 Danish cases with multiple sclerosis and 148 matched healthy control subjects, we performed shotgun sequencing of fecal microbial DNA and associated bacterial and viral microbiota findings with plasma cytokines, blood cell gene expression profiles, and disease activity. RESULTS: We found 61 bacterial species that were differentially abundant when comparing all multiple sclerosis cases with healthy controls, among which 31 species were enriched in cases. A cluster of inflammation markers composed of blood leukocytes, CRP, and blood cell gene expression of IL17A and IL6 was positively associated with a cluster of multiple sclerosis-related species. Bacterial species that were more abundant in cases with disease-active treatment-naïve multiple sclerosis were positively linked to a group of plasma cytokines including IL-22, IL-17A, IFN-ß, IL-33, and TNF-α. The bacterial species richness of treatment-naïve multiple sclerosis cases was associated with number of relapses over a follow-up period of 2 years. However, in non-disease-active cases, we identified two bacterial species, Faecalibacterium prausnitzii and Gordonibacter urolithinfaciens, whose absolute abundance was enriched. These bacteria are known to produce anti-inflammatory metabolites including butyrate and urolithin. In addition, cases with multiple sclerosis had a higher viral species diversity and a higher abundance of Caudovirales bacteriophages. CONCLUSIONS: Considerable aberrations are present in the gut microbiota of patients with multiple sclerosis that are directly associated with blood biomarkers of inflammation, and in treatment-naïve cases bacterial richness is positively associated with disease activity. Yet, the finding of two symbiotic bacterial species in non-disease-active cases that produce favorable immune-modulating compounds provides a rationale for testing these bacteria as adjunct therapeutics in future clinical trials.

Social position and functional somatic disorders: The DanFunD study.

BACKGROUND AND AIM: It is generally accepted that functional somatic disorders (FSDs) are a product of biological, psychological, and social factors. Social position might be part of this complex, but the literature on this issue is currently heterogeneous and inconsistent. The aim of the present study was - in a population-based cohort - to test the hypothesis that lower social position would be associated with higher a risk of FSD. METHOD: The association between social position and FSD was examined in a cross-sectional study with various measures of social position (education as measured by vocational training; employment; cohabitation; subjective social status) and delimitations of FSD (irritable bowel syndrome, chronic fatigue syndrome, fibromyalgia, bodily distress syndrome, and symptom profiles). The associations were analyzed using logistic regressions to calculate odds ratios and 95% confidence intervals. Each social measure was analyzed independently and was adjusted for age and sex. RESULTS: Lower levels of vocational training, being unemployed, and living alone were associated with higher risk of FSD, regardless of the FSD delimitation. There was also a significant negative association between subjective evaluated social status and FSD. The associations remained after multiple adjustments, and seemed to be strongest for the more severe FSD-types. CONCLUSIONS: Lower social position is associated with higher risk of FSD, especially the more severe FSD delimitations, which might constitute an especially vulnerable group. However, the mechanisms behind the relations remain unknown.

Neuroticism and adverse life events are important determinants in functional somatic disorders: the DanFunD study.

Several psychological factors have been proposed to be associated with functional somatic disorders (FSD). However, large population-based studies investigating the importance of both personality and adverse life events (ALE) are sparse. This study aimed to investigate the association between FSD and neuroticism and the accumulated number of ALE, respectively. This cross-sectional study included a random sample of the adult Danish population (N = 7493). FSD were established by means of self-reported questionnaires and diagnostic interviews. Neuroticism was measured with the Danish version of the short-form NEO Personality Inventory. ALE were measured with the Danish version of the Cumulative Lifetime Adversity Measure. Strong positive associations were found between neuroticism and FSD, and ALE and questionnaire-based FSD. For interview-based FSD, strong positive associations were found for FSD, multi-organ type, and for the subtype of the general symptoms. The level of self-efficacy did not modify these associations, and no moderating effect of neuroticism and ALE in combination on the probability of having FSD was found. FSD were strongly associated with both neuroticism and the accumulated number of ALE, and these associations were not modified by self-efficacy. In combination, neuroticism and ALE did not have a moderating effect on the probability of having FSD.

Association between infections and functional somatic disorders: a cross-sectional population-based cohort study.

OBJECTIVES: It has been suggested that infections can trigger functional somatic disorders (FSD). However, current evidence is limited by inconsistent findings in smaller studies conducted in clinical settings within selected populations and short follow-up times. We aimed to test the hypothesis that former infections are associated with FSD using data from nationwide registries and a large population-based cohort study, the Danish Study of Functional Disorders study. DESIGN: FSD cases were identified in a cross-sectional population-based cohort and linked retrospectively to former hospital contacts with infections identified in the Danish National Patient Registry. The associations between FSD and former infections within 17 years were analysed using logistic regressions to calculate ORs and 95% CIs adjusted for age, sex and subjective social status. SETTING: A population-based cohort in Denmark examined between 2011 and 2015. PARTICIPANTS: A total of 9656 men and women aged 18-76 years. MAIN OUTCOME MEASURES: FSD measured by various delimitations, including bodily distress syndrome (BDS), irritable bowel (IB), chronic fatigue (CF), chronic widespread pain (CWP), and multiple chemical sensitivity (MCS). RESULTS: Overall, infections were associated with increased risk of all delimitations of FSD. The associations were more pronounced for multisystemic FSD. The number of prior infections increased the risk in a dose-response manner (p<0.0001). Bacterial but not viral infections were significantly associated with BDS (OR 1.69 (95% CI 1.46 to 1.96)), IB (OR 1.41 (95% CI 1.06 to 1.88)), CWP (OR 1.47 (95% CI 1.13 to 1.90)) and CF (OR 1.62 (95% CI 1.34 to 1.96)), but not MCS. CONCLUSION: Former infections leading to hospital contacts were associated with a higher risk of having FSD. These associations were more pronounced for bacterial than viral infections, and more infections increased the risk in a dose-response manner. These results tend to support the idea that severe infections could play a role in FSD.

Examine the public health impacts of functional somatic disorders using the DanFunD study.

Background: Persistent physical symptoms (e.g. pain, fatigue) are prevalent in the population and some persons may develop a functional somatic disorder (FSD). We still need to explore the limits between general bodily sensations and FSD, and great controversies exist as regard delimitation, occurrence, risk factors, prognosis, and costs of FSD in the general population. This is mainly due to the lack of focused, sufficient powered, population-based epidemiological studies. Material and Methods: The DanFunD study is the largest focused population-based study on FSD and has the potential to answer these crucial questions regarding the FSD disorders. DanFunD has its origin in the Copenhagen area of Denmark and was initiated in 2009 by an interdisciplinary team of researchers including basic scientists, clinical researchers, epidemiologists, and public health researchers. A population-based cohort of nearly 10,000 people have filled in detailed questionnaires, gone through a thorough health examination, and a biobank is established. The cohort was re-examined after five years. Results:The prevalence of FSD in the Danish population is about 10-15% and is twice as common in women as in men. Persons with FSD report impaired daily activities and low self-perceived health, which qualifies FSD as a major public health problem. The research plan to unravel the risk factors for FSD employs a bio-psycho-social approach according to a detailed plan. Preliminary results are presented, and work is in progress. Likewise, plans for assessing prognosis and health care costs are provided. Conclusion: We invite researchers in the field to collaborate on this unique data material.

Development and Validation of the Weighted Index for Childhood Adverse Conditions (WICAC).

BACKGROUND: Adverse experiences in childhood are a major public health concern, promoting social inequality in health through biopsychosocial mechanisms. So far, no known measures comprehend the complexity and variations of severity of adverse events. This study aims to develop and validate a new index: the Weighted Index for Childhood Adverse Conditions (WICAC). METHODS: The population consists of 7493 randomly invited men and women aged 18-72 years. Data were collected in 2012-2015 as part of the Danish Study of Functional Disorders (DanFunD). Content and construct validation of the WICAC was performed with the hypothesis testing of multiple biopsychosocial outcomes: cardiovascular disease, cancer, poor health, back pain, BMI, obesity, anxiety, depression, low vitality, subjective social status, lower education, smoking, and alcohol consumption. Data were analysed with binominal and linear regression models with risk ratios (RR) and mean differences (MD). RESULTS: Content validation is fitting for WICAC. The strongest associations observed were for most severe adversity: Poor Health RR = 2.16 (1.19-2.91), Anxiety RR = 3.32 (2.32-4.74), Heavy Drinking RR = 4.09 (1.85-9.04), and Subjective Social Status MD = -0.481 (-0.721-(-0.241)). Similar results were found for the remaining outcomes. Discriminative validation was undecided. CONCLUSIONS: WICAC is an adequate instrument for measuring cumulative adverse life events in childhood and adolescence for research purposes.

Normative values of short-term heart rate variability in a cross-sectional study of a Danish population. The DanFunD study.

AIMS: The autonomic nervous system includes parasympathetic and sympathetic components that monitor and regulate most of the bodily functions and play a central role in the physiology and homeostasis of the human body. Heart rate variability is a non-invasive tool for quantification of rhythmic fluctuations in heart rate that reflects the function of the autonomic nervous system. The study aims to describe the heart rate variability distribution in the general population, stratified in sex and age groups, which is currently insufficiently described. METHODS: A cross-sectional population-based study recruited participants in 10 municipalities in the western part of the greater Copenhagen area in Denmark, including 6891 men and women aged 18-72 years (participation rate was 29.5%). Short-term heart rate variability measures were obtained and related to age and gender. RESULTS: Both time and frequency domain measures showed a huge variation in the different sex and age groups. Women had a higher median heart rate than men, and the association with age was U-shaped. Measures indicating a predominance of the parasympathetic component in relation to the sympathetic component were more frequent in women and younger age groups. CONCLUSIONS: Both sex and age influence the heart rate variability in this adult Danish population. Therefore, our age- and sex-related reference values of heart rate variability in the time and frequency domain should be used in further epidemiological and clinical research.

Physiological Health and Physical Performance in Multiple Chemical Sensitivity-Described in the General Population.

Multiple chemical sensitivity (MCS) is a multifactorial somatic disorder characterized by physical reactions triggered by even extremely low levels of different airborne chemicals. In most individuals with MCS, these reactions have substantial negative impact on social, occupational, and everyday life often including limited or no engagement in physical activities. The aim of this study was to explore associations between MCS and objective measurements of anthropometry, cardiorespiratory health, and physical performance. From the Danish population-based cohort DanFunD counting 9656 participants aged 18-76 years, 1.95% (n = 188) were categorized as MCS individuals (MCS All). Of those 188, 109 participants were subcategorized as having MCS without functional somatic disorders (FSD) (MCS with no comorbid FSD). The remaining study population without any FSD were regarded controls. We used adjusted multiple linear regression analyses to evaluate associations between MCS and anthropometry, cardiorespiratory fitness, and physical performance. Compared with the general population, MCS All had less optimal body composition, increased risk of obesity, impaired cardiorespiratory fitness, and physical performance which was not seen in MCS with no comorbid FSD. MCS individuals may be inhibited to maintain an active lifestyle which can increase risk of obesity and consequently have negatively impact on general health, which may not be the case among MCS with no comorbid FSD.

Conditioned pain modulation and pain sensitivity in functional somatic disorders: The DanFunD study.

BACKGROUND: Disrupted pain regulation has been proposed as a component in functional somatic disorders (FSD). The objective of this study was to examine a general population sample, encompassing three delimitations of FSD while assessing pain sensitivity and conditioning pain modulation (CPM). METHODS: Pressure pain thresholds (PPTs) at the tibialis and trapezius muscles were recorded at baseline. During cold pressor stimulation of the hand, the tibialis PPTs were re-assessed and the difference from baseline measures defined the CPM effect. Participants (n = 2,198, 53% females) were randomly selected from the adult Danish population. FSD was established by self-reported symptom questionnaires. RESULTS: With a few exceptions, only weak associations were seen between PPTs and CPM in cases with FSD (p > .1). A high PPT was associated with lower odds of having multi-organ bodily distress syndrome (ORPPT trapezius : 0.66, 95% CI: 0.49-0.88, p = .005), with the symptom profile characterized by all symptoms (ORPPT trapezius : 0.72, 95% CI: 0.58-0.90, p = .003 and ORPPT tibialis : 0.75, 95% CI: 0.62-0.91, p = .004), and with multiple chemical sensitivity (ORPPT trapezius : 0.81, 95% CI: 0.67-0.97, p = .022). High CPM was associated with high odds of having irritable bowel (ORCPM relative : 1.22, 95% CI: 1.04-1.43, p = .013 and ORCPM absolute  = 2.66, 95% CI: 1.07-6.45, p = .033). CONCLUSION: However, only PPT measured over the trapezius muscle were still significant after correction for multiple testing for the symptom profile characterized by all symptoms. Findings from this study do not support altered pain regulation in questionnaire-based FSD which is in contrast with the existing presumption. Further epidemiological studies in this field are needed. SIGNIFICANCE: Disrupted pain regulation as measured by abnormal pain thresholds has been hypothesized as a central mechanism in Functional Somatic Disorders (FSD). The hypothesis has been raised in clinical setting where patients presented subjective and objective features of hypersensitivity. The present population-based study does not support this notion. This points to the importance of further studies into the underlying pathophysiology mechanisms of FSD.

Symptom Perceptions in Functional Disorders, Major Health Conditions, and Healthy Controls: A General Population Study.

Background: The present study investigated differences in symptom perceptions between individuals with functional disorders (FD), major health conditions, and FDs + major health conditions, respectively, and a group of healthy individuals. Furthermore, it investigated the relevance of FDs among other health-related and psychological correlates of symptom perceptions in the framework of the Common Sense Model of Self-Regulation (CMS). Method: This cross-sectional study used epidemiological data from the Danish Study of Functional Disorders part two (N = 7,459 participants, 54% female, 51.99 ± 13.4 years). Symptom perceptions were assessed using the Brief Illness Perception Questionnaire (B-IPQ) and compared between the four health condition groups. Multiple regression analyses were performed to examine associations between symptom perceptions, FDs, and other health-related and psychological correlates from the CMS framework. Results: Individuals with FDs (n = 976) and those with FDs + major health conditions (n = 162) reported less favorable symptom perceptions compared to the other two groups, particularly regarding perceived consequences, timeline, and emotional representations (effect size range Cohen's d = 0.12-0.66). The presence of a FD was significantly associated with all B-IPQ items, even in the context of 16 other relevant health-related and psychological correlates from the CMS framework, whereas symptom presence last year or last week was not. Conclusion: In the general population, symptom perceptions seem to play a more salient role in FD than in individuals with well-defined physical illness. Symptom perceptions should therefore be targeted in both primary and secondary interventions for FDs.