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  • 1. Agréus, Lars
    et al.
    Hellström, Per M.
    Talley, Nicholas J.
    Wallner, Bengt
    Forsberg, Anna
    Vieth, Michael
    Veits, Lothar
    Björkegren, Karin
    Engstrand, Lars
    Andreasson, Anna
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Towards a healthy stomach? Helicobacter pylori prevalence has dramatically decreased over 23 years in adults in a Swedish community2016In: United European Gastroenterology journal, ISSN 2050-6406, E-ISSN 2050-6414, Vol. 4, no 5, 686-696 p.Article in journal (Refereed)
    Abstract [en]

    Background In Western countries the prevalence of Helicobacter pylori (H. pylori) infection may be declining but there is a lack of recent longitudinal population studies. We evaluated the changing epidemiology over a 23-year period in Sweden. Materials and methods In 1989, the validated Abdominal Symptom Questionnaire (ASQ) was mailed to a random sample of inhabitants (ages 22-80 years) in a Swedish community, and 1097 (87%) responded. H. pylori serology was analysed in a representative subsample (n=145). Twenty-three years later, the ASQ was mailed again using similar selection criteria, and 388 out of 1036 responders had an upper endoscopy with assessment of H. pylori and corpus atrophy status. Results The prevalence of positive H. pylori serology decreased from 37.9% (1989) to 15.8% (2012), corresponding to a decrease in odds of 75% per decade (odds ratio (OR): 0.25; 95% confidence interval (CI): 0.11-0.59, p=0.001) independent of age, gender, body mass index (BMI) and level of education, with a pattern consistent with a birth cohort effect. The prevalence increased with increasing age (p=0.001). The prevalence of H. pylori on histology in 2012 was 11.4% (95% CI 8.6-15.0). The prevalence of corpus atrophy on serology and/or histology in 2012 was 3.2% (95% CI 1.8-5.5); all cases were 57 years old. Conclusion The stomach is healthier in 2012 compared with 1989. H. pylori prevalence in adults has decreased over the last two decades to a level where clinical management might be affected.

  • 2.
    Andreasson, Anna
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Carlsson, A C
    Wändell, P E
    High levels of leptin are associated with poor self-rated health in men and women with type 2 diabetes treated with metformin.2013In: NMCD. Nutrition Metabolism and Cardiovascular Diseases, ISSN 0939-4753, E-ISSN 1590-3729, Vol. 23, no 2, e11-2 p.Article in journal (Refereed)
  • 3.
    Andreasson, Anna
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden; Macquarie University, Australia.
    Carlsson, Axel C.
    Önnerhag, Kristina
    Hagström, Hannes
    Waist/Hip Ratio Better Predicts Development of Severe Liver Disease Within 20 Years Than Body Mass Index: A Population-based Cohort Study2017In: Clinical Gastroenterology and Hepatology, ISSN 1542-3565, E-ISSN 1542-7714, Vol. 15, no 8, 1294-+ p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND & AIMS: Obesity, commonly assessed based on body mass index (BMI), is associated with an increased risk for severe liver disease. It is not known if other measures of body composition are better determinants of risk for severe liver disease, and/or if these differ between women and men. We investigated the body composition measures that best predict the development of severe liver disease. METHODS: We collected data from the Malmo Diet and Cancer study in Sweden, comprising 16,784 women and 10,833 (mean age, 58.1 years at baseline), and followed patients for a median 19.8 years. We analyzed data on measures of body composition including BMI, waist/hip ratio, and others. We determined whether subjects were diagnosed with severe liver disease, or died from severe liver disease, until the end of 2014 using Swedish national registers. Associations between body composition measures and severe liver disease were assessed using Cox regression models, stratified by sex and adjusted for age, alcohol consumption, smoking, education, and physical activity. RESULTS: All studied measures of body composition were significantly associated with severe liver disease. Waist/hip ratio was the best predictor of severe liver disease in women (hazard ratio [HR] per standard deviation increment, 1.30; 95% confidence interval [CI], 1.16-1.46) and men (HR, 1.46; 95% CI, 1.31-1.63). BMI had the lowest HR in women (HR, 1.12; 95% CI, 1.00-1.27) and men (HR, 1.26; 95% CI, 1.12-1.42). The association between waist/hip ratio and development of liver disease was independent of BMI. CONCLUSIONS: In a Swedish population-based cohort study, we associated all measures of body composition with risk of severe liver disease. However, measures of abdominal obesity were best at predicting development of severe liver disease.

  • 4.
    Andreasson, Anna
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Jones, M
    Walker, M
    Talley, N
    Nyhlin, H
    Agréus, L
    Prediction pathways for innate immune pathology, IBS,anxiety and depression in a general population (The POPCOL Study)2013In: Prediction pathways for innate immune pathology, IBS,anxiety and depression in a general population (The POPCOL Study), 2013, A237- p.Conference paper (Refereed)
  • 5.
    Andreasson, Anna N.
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Schiller, Helena
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Kecklund, Göran
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Contemplate your symptoms and re-evaluate your health2015In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 49, e38-e39 p.Article in journal (Refereed)
    Abstract [en]

    Bodily signals and how these are interpreted affect self-ratings of health. It is thus reasonable that appraisals of health are affected by imminent exposures and disease primes. We aimed to investigate whether self-ratings of health are affected by a symptom rating and if changes are substantiated in persons who report more symptoms. We used data from 813 persons who completed a questionnaire daily for 21 consecutive days. The questionnaire included a one-item self-rating of health (“pre-SRH”; 1 = excellent, 7 = very poor), a subsequent 26-item rating of physical and mental symptoms and thereafter a second (identical) self-rating of health (“post-SRH”). Paired t-tests were used to test for differences between pre-SRH and post-SRH. Mixed effect regression models were used to calculate the interaction effect of pre-SRH and symptom score on post-SRH adjusted for gender, age and if the person had been working that day (13545 observations). SRH worsened significantly (p  <<.0001) after the symptom rating, from 2.72 pre-SRH (95%CI:−2.70–2.74) to 2.77 post-SRH (95%CI:2.75–2.79). There was a significant interaction between pre-SRH and symptoms on post-SRH so that persons who reported more symptoms changed their post-SRH rating to a higher degree than those who reported fewer symptoms, irrespective of their subjective health status. The results support the notion that subjective health perception is affected by focus of attention, and that the effect depends on level of symptoms.

  • 6.
    Andreasson, Anna N.
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Wicksell, B
    Karshikoff, B
    Lodin, J
    Axelsson, J
    Olgart Höglund, C
    Development and preliminary validation of the Sickness Questionnaire (SicknessQ)2013In: Development and preliminary validation of the Sickness Questionnaire (SicknessQ), 2013, e14- p.Conference paper (Refereed)
  • 7.
    Andreasson, Anna Nixon
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Kristenson, Margareta
    Betydelsen av självskattad hälsa2012In: Hälsofrämjande möten: från barnhälsovård till palliativ vård / [ed] Anna Hertting, Margareta Kristenson, Lund: Studentlitteratur , 2012, 1, 45-52 p.Chapter in book (Other academic)
  • 8.
    Andreasson, Anna Nixon
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet.
    Szulkin, Robert
    Undén, Anna-Lena
    von Essen, Jan
    Nilsson, Lars-Göran
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet.
    Inflammation and positive affect are associated with subjective health in women of the general population2013In: Journal of Health Psychology, ISSN 1359-1053, E-ISSN 1461-7277, Vol. 18, no 3, 311-320 p.Article in journal (Refereed)
    Abstract [en]

    Poor subjective health has been associated with higher levels of inflammatory cytokines. We investigated whether such an association would apply to women of the general population. Levels of cytokines, affect and subjective health were assessed in 347 women of the general population aged 45 to 90 years. Higher levels of interleukin-6 were associated with poor subjective health, especially in participants over 65 years of age. Positive affect was a more robust determinant of subjective health than negative affect. The presence of low-grade inflammation and absence of positive affect, rather than presence of negative affect, may be important determinants of subjective health.

  • 9.
    Andreasson, Anna Nixon
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Undén, Anna-Lena
    Elofsson, Stig
    Stockholm University, Faculty of Social Sciences, Department of Social Work.
    Brismar, Kerstin
    Leptin and adiponectin: Distribution and associations with cardiovascular risk factors in men and women of the general population2012In: American Journal of Human Biology, ISSN 1042-0533, E-ISSN 1520-6300, Vol. 24, no 5, 595-601 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: In view of the increasing prevalence of obesity worldwide, understanding the role of the recently discovered adipokines leptin and adiponectin is of high clinical relevance. The aim of the present study was to assess the association between levels of leptin and adiponectin with age, known cardiovascular risk factors and to establish whether there are differences between men and women of the general population.

    METHODS: A total of 98 men and 107 women of the general population, aged between 20 and 74 years, underwent a medical examination at a clinical research center and fasting morning blood samples were also taken.

    RESULTS: Leptin (mean 7.5 μg l(-1) in men and 16.0 μg l(-1) in women) and adiponectin (mean 7.3 mg l(-1) in men and 11.9 mg l(-1) in women) levels were higher in women than men (Ps < 0.001). Both leptin and adiponectin levels increased with advancing age in both men and women (Ps < 0.05). Leptin was highly associated with factors for metabolic syndrome in men while in women, leptin was highly associated with inflammatory factors. Adiponectin was associated with blood lipids in both men and women, and glucose homeostasis more in women than in men.

    CONCLUSIONS: Leptin and adiponectin levels were ∼2 times and 1.5 times higher in women than in men, respectively. In addition, although leptin and adiponectin were associated to CVD risk factors in both men and women, we observed differences in specific CVD risk factor groups between men and women. These differences may be due to different regulatory mechanisms and effects of these adipokines in men and women.

  • 10. Carlsson, A C
    et al.
    Nixon Andreasson, Anna
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Wändell, P E
    Poor self-rated health is not associated with a high total allostatic load in type 2 diabetic patients--but high blood pressure is2011In: Diabetes & Metabolism, ISSN 1262-3636, Vol. 37, no 5, 446-51 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Allostatic load has been linked to self-rated health (SRH), cardiovascular disease and mortality in non-diabetic individuals. The aim of this study was to construct an allostatic load score and to find any correlations with SRH.

    METHODS: The subjects included in the study came from a randomized, controlled trial of type 2 diabetes. Blood samples were drawn, urine was collected for 24h, and questionnaires, including SRH, were filled out on three occasions: at baseline; after the 10-week intervention; and at a follow-up 3 months after the intervention. Allostatic load was estimated using a wide range of variables, including systolic and diastolic blood pressure, pulse pressure, cortisol, catecholamines, HbA(1c), insulin, plasma glucose and waist circumference.

    RESULTS: There was no association between SRH and allostatic load. However, three other components were significantly correlated with allostatic load at the baseline investigation and the two follow-up investigations - namely, systolic blood pressure, diastolic blood pressure and HbA(1c).

    CONCLUSION: The absence of an association between allostatic load and SRH in diabetic individuals contrasts with previous findings in non-diabetic women, and shows that it is hazardous to apply findings in one population to another, especially diabetic and non-diabetic populations.

  • 11. Carstens, A
    et al.
    Fahlen, A
    Lundin, D
    Andreasson, Anna N.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Agréus, L
    Engstrand, L
    Halfvarson, J
    The faecal flora does not reflect the colonic musicalflora. A 454, pyrosequencing study of a population-based cohort of healthyindividuals2013Conference paper (Refereed)
  • 12. Ek, W
    et al.
    Ripke, S
    Zucchelli, M
    Niesler, B
    Schmidt, P
    Pedersen, N
    Magnusson, P
    Talley, N
    Holiday, L
    Houghton, L
    Gazouli, M
    Karamanolis, G
    Barbaro, M
    Colucci, R
    Assadi, G
    Karling, P
    Walter, S
    Ohlsson, B
    Tornblom, H
    Bresso, G
    Andreasson, Anna N.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Dlugosz, A
    Simren, M
    Agreus, L
    Boeckxstaens, G
    Bellini, M
    Barbara, G
    Lindberg, G
    Daly, M
    Camilleri, M
    Wouters, M
    D´Amato, M
    Exploring the genetics of irritable bowel syndrome: AGWA study in the general population and replication in multi-nationalcase-control cohorts2013Conference paper (Refereed)
  • 13. Ek, Weronica E.
    et al.
    Reznichenko, Anna
    Ripke, Stephan
    Niesler, Beate
    Zucchelli, Marco
    Rivera, Natalia V.
    Schmidt, Peter T.
    Pedersen, Nancy L.
    Magnusson, Patrik
    Talley, Nicholas J.
    Holliday, Elizabeth G.
    Houghton, Lesley
    Gazouli, Maria
    Karamanolis, George
    Rappold, Gudrun
    Burwinkel, Barbara
    Surowy, Harald
    Rafter, Joseph
    Assadi, Ghazaleh
    Li, Ling
    Papadaki, Evangelia
    Gambaccini, Dario
    Marchi, Santino
    Colucci, Rocchina
    Blandizzi, Corrado
    Barbaro, Raffaella
    Karling, Pontus
    Walter, Susanna
    Ohlsson, Bodil
    Törnblom, Hans
    Bresso, Francesca
    Andreasson, Anna
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Dlugosz, Aldona
    Simrén, Magnus
    Agréus, Lars
    Lindberg, Greger
    Boeckxstaens, Guy
    Bellini, Massimo
    Stanghellini, Vincenzo
    Barbara, Giovanni
    Daly, Mark J.
    Camilleri, Michael
    Wouters, Mira M.
    D'Amato, Mauro
    Exploring the genetics of irritable bowel syndrome: a GWA study in the general population and replication in multinational case-control cohorts2015In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 64, no 11, 1774-1782 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: IBS shows genetic predisposition, but adequately powered gene-hunting efforts have been scarce so far. We sought to identify true IBS genetic risk factors by means of genome-wide association (GWA) and independent replication studies.

    DESIGN: We conducted a GWA study (GWAS) of IBS in a general population sample of 11 326 Swedish twins. IBS cases (N=534) and asymptomatic controls (N=4932) were identified based on questionnaire data. Suggestive association signals were followed-up in 3511 individuals from six case-control cohorts. We sought genotype-gene expression correlations through single nucleotide polymorphism (SNP)-expression quantitative trait loci interactions testing, and performed in silico prediction of gene function. We compared candidate gene expression by real-time qPCR in rectal mucosal biopsies of patients with IBS and controls.

    RESULTS: One locus at 7p22.1, which includes the genes KDELR2 (KDEL endoplasmic reticulum protein retention receptor 2) and GRID2IP (glutamate receptor, ionotropic, delta 2 (Grid2) interacting protein), showed consistent IBS risk effects in the index GWAS and all replication cohorts and reached p=9.31×10(-6) in a meta-analysis of all datasets. Several SNPs in this region are associated with cis effects on KDELR2 expression, and a trend for increased mucosal KDLER2 mRNA expression was observed in IBS cases compared with controls.

    CONCLUSIONS: Our results demonstrate that general population-based studies combined with analyses of patient cohorts provide good opportunities for gene discovery in IBS. The 7p22.1 and other risk signals detected in this study constitute a good starting platform for hypothesis testing in future functional investigations.

  • 14. Ethier, J-F.
    et al.
    Curcin, V.
    Barton, A.
    McGilchrist, M. M.
    Bastiaens, H.
    Andreasson, Anna
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Rossiter, J.
    Zhao, L.
    Arvanitis, T. N.
    Taweel, A.
    Delaney, B. C.
    Burgun, A.
    Clinical Data Integration Model: Core Interoperability Ontology for Research Using Primary Care Data2015In: Methods of Information in Medicine, ISSN 0026-1270, Vol. 54, no 1, 16-23 p.Article in journal (Refereed)
    Abstract [en]

    Introduction: This article is part of the Focus Theme of Methods of Information in Medicine on "Managing Interoperability and Complexity in Health Systems". Background: Primary care data is the single richest source of routine health care data. However its use, both in research and clinical work, often requires data from multiple clinical sites, clinical trials databases and registries. Data integration and interoperability are therefore of utmost importance. Objectives: TRANSFoRm's general approach relies on a unified interoperability frame-work, described in a previous paper. We developed a core ontology for an interoperability framework based on data mediation. This article presents how such an ontology, the Clinical Data Integration Model (CDIM), can be designed to support, in conjunction with appropriate terminologies, biomedical data federation within TRANSFoRm, an EU FP7 project that aims to develop the digital infrastructure for a learning healthcare system in European Primary Care. Methods: TRANSFoRm utilizes a unified structural /terminological interoperability framework, based on the local-as-view mediation paradigm. Such an approach mandates the global information model to describe the domain of interest independently of the data sources to be explored. Following a requirement analysis process, no ontology focusing on primary care research was identified and, thus we designed a realist ontology based on Basic Formal Ontology to support our framework in collaboration with various terminologies used in primary care. Results: The resulting ontology has 549 classes and 82 object properties and is used to support data integration for TRANSFoRm's use cases. Concepts identified by researchers were successfully expressed in queries using CDIM and pertinent terminologies. As an example, we illustrate how, in TRANSFoRm, the Query Formulation Workbench can capture eligibility criteria in a computable representation, which is based on CDIM. Conclusion: A unified mediation approach to semantic interoperability provides a flexible and extensible framework for all types of interaction between health record systems and research systems. CDIM, as core ontology of such an approach, enables simplicity and consistency of design across the heterogeneous software landscape and can support the specific needs of EHR-driven phenotyping research using primary care data.

  • 15. Forsberg, Anna
    et al.
    Kjellström, Lars
    Andreasson, Anna
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden .
    Jaramillo, Edgar
    Rubio, Carlos A.
    Björck, Erik
    Agréus, Lars
    Talley, Nicholas J.
    Lindblom, Annika
    Colonoscopy findings in high-risk individuals compared to an average-risk control population2015In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 50, no 7, 866-874 p.Article in journal (Refereed)
    Abstract [en]

    Background and aims: There is clear evidence of reduced morbidity and mortality from regular colonoscopy programs in patients with Lynch syndrome (LS). Today, also individuals with empirically increased risks of colorectal cancer (CRC) are offered colonoscopic surveillance. The aim was to compare the findings at the first screening colonoscopy in LS carriers, and individuals with an increased risk of bowel cancer due to family history of CRC with a control population. Methods: Altogether 1397 individuals with an increased risk for CRC were divided in four risk groups: one with LS carriers and three groups with individuals with different family history of CRC. The findings were compared between the different risk groups and a control group consisting of 745 individuals from a control population who took part in a population-based colonoscopy study. Results: In LS, 30% of the individuals had adenomas and 10% advanced adenomas. The corresponding figures in the other risk groups were 14-24% and 4-7%, compared with 10% and 3% in the control group. The relative risk of having adenomas and advanced adenomas was, compared to controls, significantly higher for all risk groups except the group with the lowest risk. Age was a strong predictor for adenomas and advanced adenomas in both risk individuals and controls. Conclusions: Individuals with a family history of CRC have a high prevalence and cumulative risk of adenomas and advanced adenomas, and screening is motivated also in this risk group.

  • 16. Forsberg, Anna M
    et al.
    Kjellström, Lars
    Agréus, Lars
    Nixon Andreasson, Anna
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Nyhlin, Henry
    Talley, Nicholas J
    Björck, Erik
    Prevalence of colonic neoplasia and advanced lesions in the normal population: a prospective population-based colonoscopy study.2012In: Scandinavian journal of gastroenterology, ISSN 1502-7708, Vol. 47, no 2, 184-90 p.Article in journal (Refereed)
    Abstract [en]

    Abstract Objective. There are few prospective studies of the prevalence of colonic neoplasia in the normal population. In order to properly evaluate screening-protocols for colorectal cancer in risk groups (e.g., older subjects or those with a family history), it is essential to know the prevalence of adenomas and cancer in the normal population. Methods. A prospective population-based colonoscopy study on 745 individuals born in Sweden aged 19-70 years was conducted (mean age 51.1 years). All polyps seen were retrieved and examined. Results. Out of the 745 individuals 27% had polyps, regardless of kind. Adenomas were found in 10% of the individuals and finding of adenomas was positively correlated to higher age. Men had adenomas in 15% and women in 6% of the cases. Women had a right-sided dominance of adenomas. Hyperplastic polyps were seen in 21% of the individuals. The presence of hyperplastic polyps was significantly positively correlated to the presence of adenomas. Advanced adenomas were seen in 2.8% of the study participants, but no cancers were detected. Conclusion. One in 10 healthy subjects had an adenoma but advanced adenomas were uncommon. Men and women have a different adenoma prevalence and localization. The results provide baseline European data for evaluating colonoscopy screening-protocols for colorectal cancer risk groups, and the findings may have implications for colon cancer screening in the normal, otherwise-healthy population.

  • 17. Hagström, Hannes
    et al.
    Stål, Per
    Hultcrantz, Rolf
    Hemmingsson, Tomas
    Stockholm University, Faculty of Social Sciences, Centre for Social Research on Alcohol and Drugs (SoRAD). Karolinska Institutet, Sweden .
    Andreasson, Anna
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden .
    Overweight in late adolescence predicts development of severe liver disease later in life: A 39 years follow-up study2016In: Journal of Hepatology, ISSN 0168-8278, E-ISSN 1600-0641, Vol. 65, no 2, 363-368 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND & AIMS: The increased prevalence of overweight has been suggested to contribute to the worldwide increase in liver diseases. We investigated if body mass index (BMI) in late adolescence predicts development of severe liver disease later in life.

    METHODS: We performed a cohort study using data from 44,248 men (18-20years) conscribed to military service in Sweden between 1969 and 1970. Outcome data were collected from national registers to identify any diagnosis of severe liver disease (i.e., diagnosis of decompensated liver disease, cirrhosis or death in liver disease) until the end of 2009. A Cox regression model was applied using BMI as independent variable. The model was adjusted for use of alcohol, use of narcotics, smoking, high blood pressure and cognitive ability at time of conscription.

    RESULTS: During a follow-up period of a mean of 37.8years, 393 men were diagnosed with severe liver disease (mean time to diagnosis 24.7years). BMI (Hazard ratio [HR]=1.05 for each unit increase in BMI, 95% confidence interval [CI]: 1.01-1.09, p=0.008) and overweight (HR=1.64 for BMI 25-30 compared to BMI 18.5-22.5, 95% CI: 1.16-2.32, p=0.006) were associated with an increased risk of development of severe liver disease.

    CONCLUSIONS: Being overweight in late adolescence is a significant predictor of severe liver disease later in life in men.

    LAY SUMMARY: We investigated close to 45,000 Swedish men in their late teens enlisted for conscription in 1969-1970. After almost 40years of follow-up, we found that being overweight was a risk factor for developing severe liver disease, independent of established risk factors such as alcohol consumption.

  • 18. Hansdotter, Ida
    et al.
    Björ, Ove
    Andreasson, Anna
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Agreus, Lars
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Hellström, Per
    Forsberg, Anna
    Talley, Nicholas J.
    Vieth, Michael
    Wallner, Bengt
    Hill classification is superior to the axial length of a hiatal hernia for assessment of the mechanical anti-reflux barrier at the gastroesophageal junction2016In: Endoscopy International Open, ISSN 2364-3722, Vol. 4, no 3, E311-E317 p.Article in journal (Refereed)
    Abstract [en]

    Background and study aims: The pathogenesis of gastroesophageal reflux disease (GERD) is multifactorial, including the mechanical anti-reflux barrier of the gastroesophageal junction. This barrier can be evaluated endoscopically in two ways: by measuring the axial length of any hiatal hernia present or by assessing the gastroesophageal flap valve. The endoscopic measurement of axial length is troublesome because of the physiological dynamics in the area. Grading the gastroesophageal flap valve is easier and has proven reproducible. The aim of the present study was to compare the two endoscopic grading methods with regard to associations with GERD. Patients and methods: Population-based subjects underwent endoscopic examination assessing the axial length of hiatus hernia, the gastroesophageal flap valve using the Hill classification, esophagitis using the Los Angeles (LA) classification, and columnar metaplasia using the Z-line appearance (ZAP) classification. Biopsies were taken from the squamocolumnar junction to assess the presence of intestinal metaplasia. Symptoms were recorded with the validated Abdominal Symptom Questionnaire. GERD was defined according to the Montreal definition. Results: In total, 334 subjects were included in the study and underwent endoscopy; 86 subjects suffered from GERD and 211 presented no symptoms or signs of GERD. Based on logistic regression, the estimated area under the curve statistic (AUC) for Hill (0.65 [95 % CI 0.59-0.72]) was higher than the corresponding estimate for the axial length of a hiatal hernia (0.61 [95 % CI 0.54-0.68]), although the difference was not statistically significant (P=0.225). Conclusion: From our data, and in terms of association with GERD, the Hill classification was slightly stronger compared to the axial length of a hiatal hernia, but we could not verify that the Hill classification was superior as a predictor. The Hill classification may replace the axial length of a hiatal hernia in the endoscopic assessment of the mechanical anti-reflux barrier of the gastroesophageal junction.

  • 19. Henström, Maria
    et al.
    Hadizadeh, Fatemeh
    Beyder, Arthur
    Bonfiglio, Ferdinando
    Zheng, Tenghao
    Assadi, Ghazaleh
    Rafter, Joseph
    Bujanda, Luis
    Agreus, Lars
    Andreasson, Anna
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska institutet, Sweden.
    Dlugosz, Aldona
    Lindberg, Greger
    Schmidt, Peter T.
    Karling, Pontus
    Ohlsson, Bodil
    Talley, Nicholas J.
    Simren, Magnus
    Walter, Susanna
    Wouters, Mira
    Farrugia, Gianrico
    D'Amato, Mauro
    TRPM8 polymorphisms associated with increased risk of IBS-C and IBS-M2017In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 66, no 9, 1725-1727 p.Article in journal (Refereed)
  • 20. Holliday, Elizabeth G
    et al.
    Attia, John
    Hancock, Stephen
    Koloski, Natasha
    McEvoy, Mark
    Peel, Roseanne
    D'Amato, Mauro
    Agréus, Lars
    Nyhlin, Henry
    Andreasson, Anna
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Almazar, Ann E
    Saito, Yuri A
    Scott, Rodney J
    Talley, Nicholas J
    Genome-wide association study identifies two novel genomic regions in irritable bowel syndrome.2014In: American Journal of Gastroenterology, ISSN 0002-9270, E-ISSN 1572-0241, Vol. 109, no 5, 770-772 p.Article in journal (Refereed)
  • 21. Jankipersadsing, Soesma A.
    et al.
    Hadizadeh, Fatemeh
    Bonder, Marc Jan
    Tigchelaar, Ettje F.
    Deelen, Patrick
    Fu, Jingyuan
    Andreasson, Anna
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Agreus, Lars
    Walter, Susanna
    Wijmenga, Cisca
    Hysi, Pirro
    D'Amato, Mauro
    Zhernakova, Alexandra
    A GWAS meta-analysis suggests roles for xenobiotic metabolism and ion channel activity in the biology of stool frequency2017In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 66, no 4, 756-758 p.Article in journal (Refereed)
  • 22. Järbrink-Sehgal, M. Ellionore
    et al.
    Andreasson, Anna
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Talley, Nicholas J.
    Agréus, Lars
    Song, Jeong-Yeop
    Schmidt, Peter T.
    Symptomatic Diverticulosis Is Characterized By Loose Stools2016In: Clinical Gastroenterology and Hepatology, ISSN 1542-3565, E-ISSN 1542-7714, Vol. 14, no 12, 1763-1770 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND & AIMS: Symptomatic uncomplicated diverticular disease is considered to be a discreet clinical entity distinct from irritable bowel syndrome (IBS), but population-based data are unavailable. We aimed to investigate the prevalence and location of diverticulosis in the general population, and its association with colonic symptoms and mental health. We propose that individuals with diverticulosis would report more constipation and IBS.

    METHODS: We performed a population-based study of randomly selected adults born in Sweden (age, 18-70 y; 57.2% women); 745 received a gastroenterology consultation, completed validated abdominal symptom and mental health questionnaires, and were examined by colonoscopy. Logistic regression was used to calculate the associations between diverticulosis and age, sex, gastrointestinal symptoms, anxiety, depression, and self-rated health.

    RESULTS: Among the 742 participants (54.6% women), 130 (17.5%) had diverticulosis. Age was the strongest predictor of diverticulosis (P < .001), and diverticulosis was rare in participants younger than 40 years (0.7%). All participants with diverticulosis had sigmoid involvement. Participants with diverticulosis were more likely to report loose stools (odds ratio [OR], 1.88; 95% confidence interval [CI], 1.20-2.96), urgency (OR, 1.64; 95% CI, 1.02-2.63), passing mucus (OR, 2.26; 95% CI, 1.08-4.72), and a high stool frequency (OR, 2.02; 95% CI, 1.11-3.65). Diverticulosis was associated with abdominal pain (OR, 2.10; 95% CI, 1.01-4.36; P = .047) and diarrhea-predominant IBS (OR, 9.55; 95% CI, 1.08-84.08; P = .04) in participants older than 60 years. The presence of anxiety and depression and self-rated health were similar in participants with and without diverticulosis.

    CONCLUSIONS: The prevalence of diverticulosis is age-dependent. Diverticulosis is associated with diarrhea in subjects across all age ranges. In subjects older than age 60, diverticulosis is associated with abdominal pain and diarrhea-predominant IBS.

  • 23. Kjellström, Lars
    et al.
    Molinder, Herdis
    Agreus, Lars
    Nyhlin, Henry
    Talley, Nicholas J.
    Andreasson, Anna
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet.
    A randomly selected population sample undergoing colonoscopy: prevalence of the irritable bowel syndrome and the impact of selection factors2014In: European Journal of Gastroenterology and Hepathology, ISSN 0954-691X, E-ISSN 1473-5687, Vol. 26, no 3, 268-275 p.Article in journal (Refereed)
    Abstract [en]

    ObjectiveTo analyse the epidemiology of irritable bowel syndrome (IBS) symptoms in a random sample of the general population and in a subsample consenting to a colonoscopy, and to what extent this introduces symptom selection bias.Materials and methodsOverall, 3347 randomly selected Swedish adults aged 18-70 years were mailed the validated Abdominal Symptom Questionnaire (ASQ). Responders (n=2293; 68.5%) were contacted by phone, and 745 consented to a colonoscopy. All nonresponders were contacted by phone; 265 were reached and asked seven key ASQ questions. Colonoscopy participants also completed the Rome II Modular Questionnaire.ResultsThe prevalence of IBS on the basis of the mailed ASQ (troublesome abdominal pain and bowel disturbance in the past 3 months) was 26.2% [95% confidence interval (CI): 24.4-28.0] among the ASQ responders and 36.6% (95% CI: 33.2-40.1) among the colonoscopy participants (P<0.001). Nonresponders had a lower prevalence of IBS (15.8%; 95% CI: 11.4-20.3, P<0.001) than ASQ responders. Colonoscopy participants were slightly older than noncolonoscoped participants completing the ASQ (P<0.001), but men and women were equally represented and no significant socioeconomic differences were identified. The prevalence of IBS was 14.8% (95% CI: 12.2-17.5) on the basis of the Rome II Modular Questionnaire in colonoscopy participants and 14.5% (95% CI: 11.9-17.2) when visible inflammatory disease was excluded. Of the colonoscopy participants, 31.9% (95% CI: 28.5-35.3) were symptom free.ConclusionIBS symptoms are common and rarely explained by visible inflammatory disease or cancer. There was a modest selection bias by IBS in participants accepting a screening colonoscopy, but still, one-third were symptom free. Thus, conclusions for the general population can be made from findings in the study cohort.

  • 24.
    Lasselin, Julie
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden; Universitätsklinikum Essen, Germany.
    Kemani, Mike K.
    Kanstrup, Marie
    Olsson, Gunnar L.
    Axelsson, John
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Andreasson, Anna
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Wicksell, Rikard K.
    Low-grade inflammation may moderate the effect of behavioral treatment for chronic pain in adults2016In: Journal of behavioral medicine, ISSN 0160-7715, E-ISSN 1573-3521, Vol. 39, no 5, 916-924 p.Article in journal (Refereed)
    Abstract [en]

    The purpose of the present pilot study was to explore the moderating role of basal inflammation on the effects of behavioral pain treatment in 41 patients with long-standing pain. Baseline pro-inflammatory status moderated behavioral treatment outcomes: higher pre-treatment levels of Tumor Necrosis Factor (TNF)-α and Interleukin (IL)-6 were related to less improvement in pain intensity, psychological inflexibility and in mental health-related quality of life. The treatment outcomes improved in the subgroup that had low levels of pro-inflammatory cytokines at baseline, while the subjects with higher pro-inflammatory status did not. Altogether, results indicate that low-grade inflammation may influence the behavioral treatment outcomes and provide a possible explanation of the heterogeneity in treatment response.

  • 25.
    Lekander, Mats
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Karshikoff, Bianka
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Johansson, Emilia
    Soop, Anne
    Fransson, Peter
    Lundström, Johan N.
    Andreasson, Anna
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Ingvar, Martin
    Petrovic, Predrag
    Axelsson, John
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Nilsonne, Gustav
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Intrinsic functional connectivity of insular cortex and symptoms of sickness during acute experimental inflammation2016In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 56, 34-41 p.Article in journal (Refereed)
    Abstract [en]

    Task-based fMRI has been used to study the effects of experimental inflammation on the human brain, but it remains unknown whether intrinsic connectivity in the brain at rest changes during a sickness response. Here, we investigated the effect of experimental inflammation on connectivity between areas relevant for monitoring of bodily states, motivation, and subjective symptoms of sickness. In a double blind randomized controlled trial, 52 healthy volunteers were injected with 0.6 ng/kg LPS (lipopolysaccharide) or placebo, and participated in a resting state fMRI experiment after approximately 2h 45 minutes. Resting state fMRI data were available from 48 participants, of which 28 received LPS and 20 received placebo. Bilateral anterior and bilateral posterior insula sections were used as seed regions and connectivity with bilateral orbitofrontal and cingulate (anterior and middle) cortices was investigated. Back pain, headache and global sickness increased significantly after as compared to before LPS, while a non-significant trend was shown for increased nausea. Compared to placebo, LPS was followed by increased connectivity between left anterior insula and left midcingulate cortex. This connectivity was significantly correlated to increase in back pain after LPS and tended to be related to increased global sickness, but was not related to increased headache or nausea. LPS did not affect the connectivity from other insular seeds. In conclusion, the finding of increased functional connectivity between left anterior insula and middle cingulate cortex suggests a potential neurophysiological mechanism that can be further tested to understand the subjective feeling of malaise and discomfort during a sickness response.

  • 26.
    Lekander, Mats
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Von Essen, Jan
    Schultzberg, Marianne
    Andreasson, Anna Nixon
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Garlind, Anita
    Hansson, Lars-Olof
    Nilsson, Lars-Göran
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Cytokines and memory across the mature life span of women2011In: Scandinavian Journal of Psychology, ISSN 0036-5564, E-ISSN 1467-9450, Vol. 52, no 3, 229-235 p.Article in journal (Refereed)
    Abstract [en]

    Increasing evidence suggests a role of the immune system in modulation of cognition, but details on affected memory systems are largely lacking. We therefore aimed to study the relation between selected cytokines and subsets of memory, and the impact of age in these relations. From a random population-based sample (the Betula Prospective Cohort Study), 298 women (age 45-90) were studied in terms of episodic recall and recognition, semantic fluency and knowledge, and prospective memory. Circulating cytokines of relevance for cognition and aging were measured with ELISA. Levels of interleukin (IL)-6 and sIL-2R were significantly and negatively associated with most cognitive variables, while the opposite was true for IL-1 beta. Age shared substantial variance with both cytokines and memory, and turned most correlations non-significant when controlled for together with education, BMI and presence of disease. Interactions between age and cytokines were further analyzed in multiple regressions. For IL-6, significant negative interactions with age were found for semantic fluency (p < 0.05) and prospective memory (p < 0.01), and for sIL-2R in predicting semantic knowledge (p < 0.05), indicating an increased negative impact of these cytokines on memory with increasing age. In conclusion, the study indicates a relation between cytokines and memory that appears to be largely mediated by age, and supports the suggestion that cytokine dysregulation with higher age may interact with cognitive aging.

  • 27.
    Lidberg, Lisa
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Andreasson, Anna N.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Karshikoff, B.
    Axelsson, John
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Olgart Höglund, C.
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Self-rated health in response to experimental manipulations of inflammation is mediated by sickness behavior as assessed by the sickness questionnaire2013In: Brain, Behavior, and Immunity, ISSN 0889-1591, Vol. 32, no Supplement, e34-e34 p.Article in journal (Refereed)
    Abstract [en]

    Factors that influence subjective health ratings (e.g. pain, tiredness, lack of energy) resemble immune activated sickness behavior. Accordingly, previous research has shown a relation between inflammatory cytokines and poor self-rated health. However, neither the causality of the association, nor what mediates it, is clear. In this study we investigated if a transient immune activation would affect subjective health perception and, if so, if this effect is mediated by symptoms of sickness behavior. Using a between-subject design, 51 healthy subjects were injected with either endotoxin (LPS 0.6 ng/kg) or placebo. Stimulation resulted in a peak response in pro-inflammatory cytokines after 90–120 min. Ninety minutes after injection, both perceived health framed to represent current (“How is your health right now?”) and global health (“How would you rate your general state of health”?) was significantly lower in the endotoxin condition (p’s < .01). The effect of endotoxin on self-rated health was mediated by sickness behavior as assessed by a newly developed questionnaire, Sickness Questionnaire, to 91% for current and 68 % for global health. In conclusion, it is demonstrated that a transient inflammatory activation, likely working through symptoms of sickness behavior, affects both subjectively perceived health for the moment as well as how health status on the more general level is appraised.

  • 28. Ljung Faxen, Ulrika
    et al.
    Hage, Camilla
    Andreasson, Anna
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Donal, Erwan
    Daubert, Jean-Claude
    Linde, Cecilia
    Brismar, Kerstin
    Lund, Lars H.
    HFpEF and HFrEF exhibit different phenotypes as assessed by leptin and adiponectin2017In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 228, 709-716 p.Article in journal (Refereed)
    Abstract [en]

    Background: Heart failure with reduced ejection fraction (HFrEF) exhibits a reverse metabolic profile. Whether this profile exists in HF with preserved ejection fraction (HFpEF) is unknown. We tested the hypothesis that HFpEF and HFrEF are similar regarding concentrations of and prognostic impact of leptin and adiponectin.

    Methods: In patients with HFpEF(n = 79), HFrEF(n = 84), and controls(n = 71), we analyzed serum leptin and adiponectin concentrations, their correlations, and associations with outcome.

    Results: Leptin levels in HFpEF and HFrEF were increased (p < 0.05) compared to controls; with the highest levels in HFpEF, median (IQR), 23.1 (10.2-51.0), vs. HFrEF 15.0 (6.2-33.2), and vs. controls 10.8 (5.4-18.9) ng/mL. There was no difference between HFpEF and HFrEF p=0.125 (adjusted for gender, BMI and age). Leptin was inversely associated with NT-proBNP (r = -0.364 p = 0.001) and associated with better outcome in HFrEF (HR per ln increase of leptin 0.76, 95% CI 0.58-0.99, p = 0.044) but not in HFpEF.

    Crude levels of adiponectin were similar in HFpEF: 11.8 (7.9-20.1), HFrEF: 13.7 (7.0-21.1), and controls: 10.5 (7.4-15.1) mu g/L. In men, adjusted similarly as leptin, there was no difference between HFpEF and HFrEF, p = 0.310 but, compared to controls, higher levels in HFpEF (p - 0.044) and HFrEF (p - 0.001). Adiponectin correlated positively with NT-proBNP; r = 0.396 p < 0.001 and higher levels were associated with adverse outcome only in HFrEF (HR per ln increase 2.88 (95% CI 1.02-8.14, p = 0.045).

    Conclusion: HFpEF and HFrEF share elevated levels of leptin and adiponectin. However, the concept of reverse metabolic profile could not be confirmed in HFpEF, suggesting that HFpEF might have a conventional metabolic profile, rather than a distinct HF syndrome.

  • 29. Ljung Faxén, Ulrika
    et al.
    Hage, Camilla
    Benson, Lina
    Zabarovskaja, Stanislava
    Andreasson, Anna
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska institutet, Sweden.
    Donal, Erwan
    Daubert, Jean-Claude
    Linde, Cecilia
    Brismar, Kerstin
    Lund, Lars H.
    HFpEF and HFrEF Display Different Phenotypes as Assessed by IGF-1 and IGFBP-12017In: Journal of Cardiac Failure, ISSN 1071-9164, E-ISSN 1532-8414, Vol. 23, no 4, 293-303 p.Article in journal (Refereed)
    Abstract [en]

    Background

    Anabolic drive is impaired in heart failure with reduced ejection fraction (HFrEF) but insufficiently studied in heart failure with preserved ejection fraction (HFpEF). Insulin-like growth factor 1 (IGF-1) mediates growth hormone effects and IGF binding protein 1 (IGFBP-1) regulates IGF-1 activity. We tested the hypothesis that HFpEF and HFrEF are similar with regard to IGF-1 and IGFBP-1.

    Methods and Results

    In patients with HFpEF (n = 79), HFrEF (n = 85), and controls (n = 136), we analyzed serum IGF-1 and IGFBP-1 concentrations, correlations, and associations with outcome. Age-standardized scores of IGF-1 were higher in HFpEF, median arbitrary units (interquartile range); 1.21 (0.57–1.96) vs HFrEF, 0.09 (-1.40–1.62), and controls, 0.22 (-0.47-0.96), P overall <.001. IGFBP-1 was increased in HFpEF, 48 (28–79), and HFrEF, 65 (29–101), vs controls, 27(14–35) µg/L, P overall <.001. These patterns persisted after adjusting for metabolic and HF severity confounders. IGF-1 was associated with outcomes in HFrEF, hazard ratio per natural logarithmic increase in IGF-1 SD score 0.51 (95% confidence interval 0.32–0.82, P = .005), but not significantly in HFpEF. IGFBP-1 was not associated with outcomes in either HFpEF nor HFrEF.

    Conclusion

    HFpEF and HFrEF phenotypes were similar with regard to increased IGFBP-1 concentrations but differed regarding IGF-1 levels and prognostic role. HFrEF and HFpEF may display different impairment in anabolic drive.

  • 30. Lodin, Karin
    et al.
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Syk, Jörgen
    Alving, Kjell
    Petrovic, Predrag
    Andreasson, Anna
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden; Macquarie University, Australia.
    Longitudinal co-variations between inflammatory cytokines, lung function and patient reported outcomes in patients with asthma2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 9, e0185019Article in journal (Refereed)
    Abstract [en]

    Background

    Asthma is a chronic inflammatory respiratory disorder associated with reduced lung function and poor quality of life. The condition is also associated with poor self-rated health, a major predictor of objective health trajectories. Of biological correlates to self-rated health, evidence suggests a role for inflammatory cytokines and related sickness behaviours. However, this is mainly based on cross-sectional data, and the relation has not been investigated in patients with chronic inflammatory conditions.

    Objective

    To investigate inflammatory cytokines, lung function, sickness behaviour and asthma-related quality of life as determinants of self-rated health in patients with asthma, and to investigate if these variables co-vary over time. Methods Plasma cytokines (IL-5, IL-6), lung function (FEV1), sickness behaviour, asthma-related quality of life and self-rated health were assessed in 181 patients with allergic asthma aged 18-64 years in a one-year longitudinal study. Mixed effect regression models and Spearman's correlation were performed to analyse the associations between repeated measurements.

    Results

    More sickness behaviour and poorer asthma-related quality of life were associated with poorer self-rated health (p's<0.001). In men, both low and high levels of interleukin (IL)-6 and poorer lung function were related with poorer self-rated health (p's<0.05). Over the year, improved asthma-related quality of life was associated with better self-rated health (Spearman's rho = -0.34 women,-0.36 men, p's<0.01). Further, if sickness behaviour decreased, self-rated health improved, but only in women (Rho = -0.21, p<0.05). Increased FEV1 in men was associated with an increase in IL-6 (Rho = 0.24, p<0.05) as well as improved self-rated health (Rho = -0.21, p<0.05) and asthma-related quality of life (Rho = 0.29, p<0.01) over the year.

    Conclusion

    The study highlights the importance of subjectively perceived sickness behaviour and asthma-related quality of life together with lung function as determinants of self-rated health in asthmatic patients. The importance of inflammatory activation for patient reported outcomes in chronic inflammatory conditions need further investigation.

  • 31. Molinder, Herdis
    et al.
    Agréus, Lars
    Kjellström, Lars
    Walter, Susanna
    Talley, Nicholas J.
    Andreasson, Anna
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Nyhlin, Henry
    How individuals with the irritable bowel syndrome describe their own symptoms before formal diagnosis2015In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 120, no 4, 276-279 p.Article in journal (Refereed)
    Abstract [en]

    Aim: To investigate how individuals fulfilling the Rome II criteria for irritable bowel syndrome (IBS) spontaneously described their symptoms. Method: From a general population, 1,244 randomly sampled adults were asked to describe their gastrointestinal symptoms (if any) verbally, in their own words, at a semi-structured interview. Their own descriptions were sorted into five symptom clusters. The participants independently completed a written questionnaire (the Rome II Modular Questionnaire (RMIIMQ)). Results: A total of 601 participants reported at least one gastrointestinal symptom, and 128 had IBS according to the RMIIMQ. After exclusion of organic causes, previously diagnosed IBS, or additional gastrointestinal diagnosis, 81 participants with IBS according to RMIIMQ remained. Five participants (6%) described symptoms included in the full definition of IBS, but none fulfilled the Rome II criteria completely. Abdominal pain or other IBS-related symptoms were reported by 64 (79%), and 12 (15%) did not report any IBS-like symptom. Conclusion: Previously undiagnosed individuals, who fulfil criteria for Rome II-IBS, often express their complaints in words that do not fit into the current diagnostic criteria.

  • 32. Quince, Christopher
    et al.
    Lundin, Elin E.
    Andreasson, Anna N.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Greco, Dario
    Rafter, Joseph
    Talley, Nicholas J.
    Agreus, Lars
    Andersson, Anders F.
    Engstrand, Lars
    D'Amato, Mauro
    The impact of Crohn's disease genes on healthy human gut microbiota: a pilot study2013In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 62, no 6, 952-954 p.Article in journal (Refereed)
  • 33.
    Sundelin, Tina
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Andreasson, Anna N.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Centre for Family Medicine, Sweden.
    Axelsson, J.
    Sleep loss and subjective health2013In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 32, e22Article in journal (Refereed)
    Abstract [en]

    Both insufficient sleep and subjective health predict mortality and are related to sickness-like symptoms as well as immune activation. Cross-sectional data show a strong association between sleep and subjective health, but there is a lack of experimental data that may distinguish causation from association. We investigated the effects of restricted sleep on subjective health in two experimental studies. The first study consisted of 23 subjects (11 women) who rated their subjective health twice, once after 31 h of wakefulness and once after normal sleep (8 h sleep/night). The second study had 25 subjects (14 women) who rated their subjective health after two consecutive nights with 4 h sleep/night and after normal sleep (8 h sleep/night). In the group deprived of sleep for 31 h, participants rated themselves as less healthy that day (−1.7 on a 7-point scale, p < 0.01) compared to after normal sleep. In the group with partially restricted sleep, participants also rated their health as worse compared to after normal sleep, both their current health (−0.8 on a 7-point scale, p < 0.05) and general health (−0.6 on a 5-point scale, p < 0.05). This study shows that an experimental reduction of sleep, complete as well as partial, leads to poorer subjective health. Considering the predictive qualities of this measure, future studies should determine the underlying mechanisms of the connection between insufficient sleep and worse subjective health.

  • 34. Syk, Jörgen
    et al.
    Malinovschi, Andrei
    Borres, Magnus P.
    Undén, Anna-Lena
    Andreasson, Anna
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Alving, Kjell
    Parallel reductions of IgE and exhaled nitric oxide after optimized anti-inflammatory asthma treatment2016In: Immunity Inflammation and Disease, ISSN 2050-4527, Vol. 4, no 2, 182-190 p.Article in journal (Refereed)
    Abstract [en]

    Immunoglobulin E (IgE) is crucial for the development of airway inflammation in atopic asthma, and inhibition of IgE using monoclonal antibodies is now part of asthma therapy. However, the impact of ordinary anti-inflammatory treatment on IgE is unclear. The aim of this study was to investigate if optimization of treatment with inhaled corticosteroid (ICS) and leukotriene-receptor antagonist (LTRA) according to symptoms or exhaled nitric oxide (FENO) levels over a one-year period affects IgE concentrations. Altogether, 158 relatively well-controlled but multi-sensitized asthmatics (age 18-65 years), with ongoing ICS treatment at baseline, were included in this post hoc analysis of data from a randomized, controlled trial on FENO-guided asthma therapy. Asthma control and quality of life (Juniper ACQ and mAQLQ), FENO, and serum IgE were measured at baseline and after one year. Concentrations of IgE antibodies to six common perennial aeroallergens were summed up (perennial IgE). We found that perennial and total IgE decreased by 10.2% and 16.0% (P<. 001 both comparisons). This was not related to allergen exposure, whereas the total use of ICS and LTRA during the year correlated with the reduction in perennial IgE (P = .030 and P = .013). The decrease in perennial and total IgE correlated significantly with the reduction in FENO (P<. 003 and P<. 001), and with improvements in ACQ and mAQLQ scores (P< 0.05, all comparisons). We conclude that one year of optimization of treatment with ICS and LTRA in patients with persistent atopic asthma resulted in significant decreases in total IgE and IgE antibodies; these decreases correlated with a reduction in FENO and improvements in asthma control and quality of life. Thus, IgE is reduced by ordinary asthma controller medications and the effect on IgE seems to be clinically important.

  • 35. Syk, Jörgen
    et al.
    Malinovschi, Andrei
    Johansson, Gunnar
    Undén, Anna-Lena
    Andreasson, Anna
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Alving, Kjell
    Anti-inflammatory treatment of atopic asthma guided by exhaled nitric oxide: a randomized  controlled trial2013In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 1, no 6, 639-648 p.Article in journal (Refereed)
  • 36. Walker, M M
    et al.
    Talley, J N
    Jones, M P
    Andreasson, Anna N.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Inganas, L
    Nyhlin, H
    Agreus, L
    Is Associated With Symptomsof Irritable Bowel Syndrome (IBS) in a General Population (the Popcol Study) Gastroenterology2013In: Is Associated With Symptomsof Irritable Bowel Syndrome (IBS) in a General Population (the Popcol Study) Gastroenterology, Gastroenterology , 2013, S-727- p.Conference paper (Refereed)
  • 37. Walker, Marjorie M.
    et al.
    Talley, Nicholas J.
    Inganas, Linn
    Engstrand, Lars
    Jones, Michael P.
    Nyhlin, Henry
    Agreus, Lars
    Kjellstrom, Lars
    Ost, Ake
    Andreasson, Anna N.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Colonic spirochetosis is associated with colonic eosinophilia and irritable bowel syndrome in a general population in Sweden2015In: Human Pathology, ISSN 0046-8177, E-ISSN 1532-8392, Vol. 46, no 2, 277-283 p.Article in journal (Refereed)
    Abstract [en]

    Irritable bowel syndrome (IBS) is a functional disorder defined by symptoms in the absence of overt pathology. Colonic spirochetosis (CS), defined by histologic observation of spirochetal strains of Brachyspira in colonic biopsies, is uncommon and considered of doubtful significance. We aimed to determine the prevalence of CS in the general population, identify subtle colon pathologies, and evaluate a link with symptoms of IBS. Colonoscopy was performed in 745 subjects (aged 19-70 years, mean age 51 years, 43% male) with biopsies (ileum and 4 colonic sites) from a random population sample, Stockholm, Sweden, who completed a validated questionnaire of gastrointestinal symptoms; IBS was identified by Rome III criteria. CS was identified by histology and immunohistochemistry. In a general population, 17 individuals (2.28%; 95% confidence interval, 1.2%-3.5%) were diagnosed as having CS by histology; 6 (35%) had IBS. CS was always present in the sigmoid colon, but only 14 rectal biopsies. Eosinophils were increased in colon biopsies in CS cases versus controls, in the transverse (p = .02), sigmoid colon (P = .001), and rectum (P = .0005) with subepithelial eosinophil clusters (P = .053). Lymphoid follicles (at any site) were present in 13 CS (P = .0003). There was a 3-fold increased risk of IBS in CS (odds ratio, 3.59; 95% confidence interval, 1.27-10.11; P = .015). Polyps and diverticular disease were similar in CS cases and controls. The prevalence of CS in a general population is 2% and associated with nonconstipating IBS. Colonic eosinophilia with lymphoid follicles may signify the presence of CS.

  • 38. Walter, S. A.
    et al.
    Jones, M. P.
    Talley, N. J.
    Kjellström, L.
    Nyhlin, H.
    Andreasson, Anna N.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institute.
    Agreus, L.
    Abdominal pain is associated with anxiety and depression scores in a sample of the general adult population with no signs of organic gastrointestinal disease2013In: Neurogastroenterology and Motility, ISSN 1350-1925, E-ISSN 1365-2982, Vol. 25, no 9, 741-E576 p.Article in journal (Refereed)
    Abstract [en]

    Background Abdominal pain is common in the community, but only a subset meet diagnostic criteria for irritable bowel syndrome (IBS). Although anxiety and depression have been linked to IBS, the role of mood disturbances in the remainder with symptoms remains unclear. We aimed to study the associations between abdominal pain, anxiety, depression, and quality of life in the general population who were free of organic colonic disease by colonoscopy. Methods Two hundred and seventy-two randomly selected subjects from the general population, mean age 54 years (27-71), were clinically evaluated, had a colonoscopy and laboratory investigations to exclude organic gastrointestinal (GI) disease. All subjects completed GI symptom diaries for 1 week, the Rome II modular questionnaire, the Hospital Anxiety and Depression Scale, and Short Form 36. Key Results Twenty-two subjects were excluded due to organic disease; 1532 daily symptom records were available for analysis in the remainder. Thirty-four percent (n = 83) recorded at least one episode of abdominal pain on the diary. Twelve percent fulfilled Rome II criteria for IBS. Both anxiety and depression scores were higher in subjects who reported abdominal pain vs those who did not (P < 0.0005 and P < 0.0005). Anxiety and depression scores independently from IBS diagnosis (Rome II) predicted pain reporting and also correlated positively with pain burden. Quality of life scores were generally lower in subjects with abdominal pain. Conclusions & Inferences Anxiety and depression are linked to functional abdominal pain, not only in subjects with IBS but also in otherwise healthy people with milder, subtle GI symptoms.

  • 39. Warnoff, Carin
    et al.
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Hemmingsson, Tomas
    Sorjonen, Kimmo
    Melin, Bo
    Andreasson, Anna
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Is poor self-rated health associated with low-grade inflammation in 43 110 late adolescent men of the general population? A cross-sectional study2016In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 6, no 4, e009440Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Self-rated health is a powerful predictor of long-term health and mortality, hence the importance of a better understanding of its biological determinants. Previous studies have shown that low-grade inflammation is associated with poor self-rated health in clinical and healthy populations, but the evidence is sparse in men and completely lacking for men in late adolescence. The aim of this study was to investigate the association between low-grade inflammation and self-rated health among conscripts. It was hypothesised that high levels of inflammatory factors would be associated with poor self-rated health.

    DESIGN: Data from 49 321 men (18-21 years) conscripted for military service in 1969 and 1970 were used. Inflammation had been measured through erythrocyte sedimentation rate (ESR). Self-rated health had been assessed on a five-point scale, and was dichotomised into Good ('Very good'/'Good'/'Fair') versus Poor ('Poor'/'Very poor'). Data from 43 110 conscripts with normal levels of ESR, and who reported self-rated health remained after exclusion of those with ESR <1 and >11 mm/h. Associations were calculated using logistic regression analyses. Adjustments were made for body mass index, socioeconomic position, inflammatory disease, emotion regulation, smoking, risky use of alcohol and physical activity.

    RESULTS: High levels of ESR were associated with higher odds for poor self-rated health (OR: 1.077 for each unit mm/h increase in ESR, 95% CI 1.049 to 1.105).

    CONCLUSIONS: The present study shows for the first time a significant association between a marker of inflammation and self-rated health in late adolescent men, adding to evidence of an association between low-grade inflammation and subjective health perception also in men, as previously demonstrated in women. Further support for inflammation as part of a general psychobiological process that underpins subjective health perception is hereby provided.

  • 40. Wändell, Per E.
    et al.
    Gigane, Bruna
    Andreasson, Anna Nixon
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Carlsson, Axel C.
    Gender differences regarding novel biomarkers and metabolic risk factors in metformin treated type 2 diabetic patients2012In: The Open Diabetes Journal, ISSN 1876-5246, Vol. 5, 13-19 p.Article in journal (Refereed)
    Abstract [en]

    We aimed to analyze associations between adiponectin, ghrelin and leptin with anthropometric and metabolic markers in men and women with Metformin-treated type 2 diabetes (n=53), recruited from a trial of relaxation therapies. Anthropometrical measures and fasting blood samples were assessed on three occasions: at baseline, and after 10 and 24 weeks: BMI, waist, HbA1c, insulin, glucose, adiponectin, leptin, fasting ghrelin, high sensitivity C-reactive protein (CRP), tumor necrosis factor α (TNF- α) and interleukin 6 (IL-6). HOMA2ir and HOMA2s were calculated from fasting glucose and insulin, and adiponectin/leptin and adiponectin/HOMA2ir ratios were calculated.In men, higher leptin and lower adiponectin/leptin ratio correlated with insulin and insulin resistance, and in women lower ghrelin with insulin and insulin resistance. In multivariate linear regression, higher levels of leptin were associated with insulin resistance among men, but not among women. Among women, insulin resistance was associated with lower adiponectin/leptin ratio and ghrelin. Factor analysis showed that leptin in women was closely related to anthropometric variables, but in men both related to anthropometric and inflammatory variables. Gender differences could indicate different pathophysiologic mechanisms of insulin resistance and type 2 diabetes among men and women, where leptin possibly could be a better marker among men, and ghrelin among women.

  • 41. Zucchelli, Marco
    et al.
    Camilleri, Michael
    Nixon Andreasson, Anna
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Bresso, Francesca
    Dlugosz, Aldona
    Halfvarson, Jonas
    Törkvist, Leif
    Schmidt, Peter T
    Karling, Pontus
    Ohlsson, Bodil
    Duerr, Richard H
    Simren, Magnus
    Lindberg, Greger
    Agreus, Lars
    Carlson, Paula
    Zinsmeister, Alan R
    D'Amato, Mauro
    Association of TNFSF15 polymorphism with irritable bowel syndrome2011In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 60, no 12, 1671-7 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Irritable bowel syndrome (IBS) is the most common gastrointestinal disorder, affecting more than 10% of the general population worldwide. Although a genetic component is suspected, unambiguous susceptibility genes have so far not been identified. This study tested the hypothesis that genes contributing to epithelial barrier integrity, control of mucosal immune responses and interactions with bacteria in the gut are associated with IBS.

    METHODS: Single nucleotide polymorphisms (SNPs) corresponding to top signals of association with Crohn's disease at 30 known susceptibility loci were tested for their effect on IBS risk in 1992 individuals from two independent case-control cohorts from Sweden and the USA. Association tests included a conservative Bonferroni correction for multiple comparisons, and were also performed on specific subgroups of patients characterised by constipation (IBS-C), diarrhoea (IBS-D) or alternating constipation and diarrhoea (IBS-A).

    RESULTS: The Crohn's disease risk allele rs4263839 G in the TNFSF15 gene was significantly associated with an increased risk of both IBS (p=2.2×10(-5); OR 1.37) and more pronouncedly, IBS-C (p=8.7×10(-7); OR 1.79) in the entire sample. Similar associations and risk effects of the same magnitude were observed in the two cohorts analysed separately. A correlation between rs4263839 genotype and TNFSF15 mRNA expression was detected both in peripheral blood and in rectal mucosal biopsies from healthy individuals (combined p=0.0033).

    CONCLUSIONS: TNFSF15 is a susceptibility gene for IBS and IBS constipation. As TL1A, the protein encoded by TNFSF15, contributes to the modulation of inflammatory responses, the results support a role of immune activation in IBS.

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