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  • 351. Berman, Anne H.
    et al.
    Wennberg, Peter
    Stockholm University, Faculty of Social Sciences, Centre for Social Research on Alcohol and Drugs (SoRAD).
    Sinadinovic, Kristina
    Changes in Mental and Physical Well-Being Among Problematic Alcohol and Drug Users in 12-Month Internet-Based Intervention Trials2015In: Psychology of Addictive Behaviors, ISSN 0893-164X, E-ISSN 1939-1501, Vol. 29, no 1, p. 97-105Article in journal (Refereed)
    Abstract [en]

    Twelve-month well-being outcomes were investigated for 835 participants in 1 of 2 randomized controlled trials offering online assessment and brief intervention for either problematic alcohol (n = 633) or drug use (n = 202). The well-being of participants who had reduced their substance use to a less problematic level (regardless of intervention) over 12 months was compared with that of participants who had maintained or increased their use. At a 12-month follow-up, the 227 alcohol trial participants with reduced use showed better well-being in comparison to the 406 with stable or increased use, in physical health and sleep quality, as well as general well-being, ability to concentrate, lower stress, better social life satisfaction and sense of control, and a lower rate of depressed mood. Among the 70 drug trial participants who had reduced their drug use over 12 months, 80% had ceased all drug use, and at follow-up they had fewer alcohol-related problems than the stable group. No differences in well-being between these groups were identified. Self-reported access to additional treatment modalities beyond the trial interventions (e.g., speaking to someone about problematic use and accessing additional Internet-based interventions) was higher among participants in both cohorts with reduced substance use in comparison to those with stable/increased use. Drug users who reduced their use accessed prescribed medication to a larger extent than those whose use remained stable or increased. Points to consider when conducting future research on well-being and problematic substance use are discussed.

  • 352. Bernard, H.
    et al.
    Faber, M.
    Wilking, H.
    Haller, S.
    Höhle, Michael
    Robert Koch Institute, Germany.
    Schielke, A.
    Ducomble, T.
    Siffczyk, C.
    Merbecks, S. S.
    Fricke, G.
    Hamouda, O.
    Stark, K.
    Werber, D.
    Large multistate outbreak of norovirus gastroenteritis associated with frozen strawberries, East Germany, 20122014In: Eurosurveillance, ISSN 1025-496X, E-ISSN 1560-7917, Vol. 19, no 8, article id pii=20719Article in journal (Refereed)
    Abstract [en]

    From 20 September through 5 October 2012, the largest recorded food-borne outbreak in Germany occurred. Norovirus was identified as the causative agent. We conducted four analytical epidemiological studies, two case–control studies and two surveys (in total 150 cases) in secondary schools in three different federal states. Overall, 390 institutions in five federal states reported nearly 11,000 cases of gastroenteritis. They were predominantly schools and childcare facilities and were supplied almost exclusively by one large catering company. The analytical epidemiological studies consistently identified dishes containing strawberries as the most likely vehicle, with estimated odds ratios ranging from 2.6 to 45.4. The dishes had been prepared in different regional kitchens of the catering company and were served in the schools two days before the peaks of the respective outbreaks. All affected institutions had received strawberries of one lot, imported frozen from China. The outbreak vehicle was identified within a week, which led to a timely recall and prevented more than half of the lot from reaching the consumer. This outbreak exemplifies the risk of large outbreaks in the era of global food trade. It underlines the importance of timely surveillance and epidemiological outbreak investigations for food safety.

  • 353. Bernard, Helen
    et al.
    Werber, Dirk
    Höhle, Michael
    Stockholm University, Faculty of Science, Department of Mathematics. Robert Koch Institute, Germany.
    Estimating the under-reporting of norovirus illness in Germany utilizing enhanced awareness of diarrhoea during a large outbreak of Shiga toxin-producing E. coli O104:H4 in 2011 - a time series analysis2014In: BMC Infectious Diseases, ISSN 1471-2334, E-ISSN 1471-2334, Vol. 14, article id 116Article in journal (Refereed)
    Abstract [en]

    Background: Laboratory- confirmed norovirus illness is reportable in Germany since 2001. Reported case numbers are known to be undercounts, and a valid estimate of the actual incidence in Germany does not exist. An increase of reported norovirus illness was observed simultaneously to a large outbreak of Shiga toxin-producing E. coli O104: H4 in Germany in 2011 - likely due to enhanced (but not complete) awareness of diarrhoea at that time. We aimed at estimating age- and sex-specific factors of that excess, which should be interpretable as (minimal) under-reporting factors of norovirus illness in Germany. Methods: We used national reporting data on laboratory-confirmed norovirus illness in Germany from calendar week 31 in 2003 through calendar week 30 in 2012. A negative binomial time series regression model was used to describe the weekly counts in 8.2 age- sex strata while adjusting for secular trend and seasonality. Overall as well as age- and sex- specific factors for the excess were estimated by including additional terms (either an O104: H4 outbreak period indicator or a triple interaction term between outbreak period, age and sex) in the model. Results: We estimated the overall under- reporting factor to be 1.76 (95% Cl 1.28- 2.41) for the first three weeks of the outbreak before the outbreak vehicle was publicly communicated. Highest under-reporting factors were here estimated for 20- 29 year-old males (2.88, 95% Cl 2.01- 4.11) and females (2.67, 95% Cl 1.87- 3.79). Under-reporting was substantially lower in persons aged < 10 years and 70 years or older. Conclusions: These are the first estimates of (minimal) under- reporting factors for norovirus illness in Germany. They provide a starting point for a more detailed investigation of the relationship between actual incidence and reporting incidence of norovirus illness in Germany.

  • 354.
    Bernard-Oettel, Claudia
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Leineweber, Constanze
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Westerlund, Hugo
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Temporary, self-employed and permanent workers: A Swedish study on work characteristics and individual well-being over time2013In: , 2013Conference paper (Refereed)
  • 355.
    Berndt, Hanna
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Gothenburg University, Sweden.
    Fors, Stefan
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Childhood living conditions, education and health among the oldest old in Sweden2016In: Ageing & Society, ISSN 0144-686X, E-ISSN 1469-1779, Vol. 36, no 3, p. 631-648Article in journal (Refereed)
    Abstract [en]

    The objectives were to investigate the associations between social and financial living conditions in childhood, education and morbidity in old age. The study population (N = 591; 76+ years old) was assembled from two nationally representative Swedish surveys, in 1968 and 2011, that together made longitudinal analysis possible. Morbidity in old age comprised self-reported measures of musculoskeletal disorders, cardiovascular disease, self-rated health and impaired mobility. There were no independent associations between adverse childhood living conditions and morbidity. However, adverse childhood living conditions were associated with an increased likelihood of low education. Moreover, low education was associated with a higher probability of health problems in old age. The results did not show any associations between adverse childhood conditions and late-life morbidity. However, adverse childhood conditions were associated with lower levels of education which, in turn, was associated with health problems and attrition from the study. These results suggest that adverse childhood conditions may indeed be associated with health and survival in old age, but mainly through mechanisms acting earlier in the lifecourse.

  • 356. Bernehäll Claesson, Inger
    et al.
    Brodin, Jane
    Stockholm University, Faculty of Social Sciences, Department of Child and Youth Studies.
    What families with children with brittle bones want to tell2002In: Child: Care, Health and Development, Vol. 28, no 4, p. 309-315Article in journal (Refereed)
    Abstract [en]

    Interviews with parents of children with brittle bones and questionnaires answered by 30 families about everyday life.

  • 357. Berner, Jessica
    et al.
    Rennemark, Mikael
    Jogréus, Claes
    Anderberg, Peter
    Sköldunger, Anders
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Wahlberg, Maria
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Elmståhl, Sölve
    Berglund, Johan
    Factors influencing Internet usage in older adults (65 years and above) living in rural and urban Sweden2015In: Health Informatics Journal, ISSN 1460-4582, E-ISSN 1741-2811, Vol. 21, no 3, p. 237-249Article in journal (Refereed)
    Abstract [en]

    Older adults living in rural and urban areas have shown to distinguish themselves in technology adoption; a clearer profile of their Internet use is important in order to provide better technological and health-care solutions. Older adults' Internet use was investigated across large to midsize cities and rural Sweden. The sample consisted of 7181 older adults ranging from 59 to 100 years old. Internet use was investigated with age, education, gender, household economy, cognition, living alone/or with someone and rural/urban living. Logistic regression was used. Those living in rural areas used the Internet less than their urban counterparts. Being younger and higher educated influenced Internet use; for older urban adults, these factors as well as living with someone and having good cognitive functioning were influential. Solutions are needed to avoid the exclusion of some older adults by a society that is today being shaped by the Internet.

  • 358. Bernhard-Oettel, C.
    et al.
    Leineweber, Constanze
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Westerlund, Hugo
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    The temporaries, theself-employed and the permanent staff: A Swedish study comparing work characteristics and individual well-being over time2013Conference paper (Refereed)
  • 359.
    Berntzon, Lotta
    et al.
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences.
    Ronnevi, L. O.
    Bergman, Birgitta
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences.
    Eriksson, Johan
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences.
    DETECTION OF BMAA IN THE HUMAN CENTRAL NERVOUS SYSTEM2015In: Neuroscience, ISSN 0306-4522, E-ISSN 1873-7544, Vol. 292, p. 137-147Article in journal (Refereed)
    Abstract [en]

    Amyotrophic lateral sclerosis (ALS) is an extremely devastating neurodegenerative disease with an obscure etiology. The amino acid beta-N-methyl-L-alanine (BMAA) produced by globally widespread phytoplankton has been implicated in the etiology of human motor neuron diseases. BMAA was recently proven to be present in Baltic Sea food webs, ranging from plankton to larger Baltic Sea organisms, some serving as important food items (fish) for humans. To test whether exposure to BMAA in a Baltic Sea setting is reflected in humans, blood and cerebrospinal fluid (CSF) from individuals suffering from ALS were analyzed, together with sex- and age-matched individuals not inflicted with ALS. Ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) and multiple reaction monitoring (MRM), in conjunction with diagnostic transitions revealed BMAA in three (12%) of the totally 25 Swedish individuals tested, with no preference for those suffering from ALS. The three BMAA-positive samples were all retrieved from the CSF, while BMAA was not detected in the blood. The data show that BMAA, potentially originating from Baltic Sea phytoplankton, may reach the human central nervous system, but does not lend support to the notion that BMAA is resident specifically in ALS-patients. However, while dietary exposure to BMAA may be intermittent and, if so, difficult to detect, our data provide the first demonstration of BMAA in the central nervous system of human individuals ante mortem quantified with UHPLC-MS/MS, and therefore calls for extended research efforts.

  • 360. Beronius, A.
    et al.
    Ågerstrand, Marlene
    Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.
    Making the most of expert judgment in hazard and risk assessment of chemicals2017In: Toxicology Research, ISSN 2045-452X, E-ISSN 2045-4538, Vol. 6, no 5, p. 571-577Article in journal (Refereed)
    Abstract [en]

    Evaluation of the reliability and relevance of toxicity and ecotoxicity studies is an integral step in the assessment of the hazards and risks of chemicals. This evaluation is inherently reliant on expert judgment, which often leads to differences between experts' conclusions regarding how individual studies can contribute to the body of evidence. The conclusions of regulatory assessment, such as establishing safe exposure levels for humans and the environment and calculations of margins of exposure, may have large consequences for which chemicals are permitted on the market and their allowed uses. It is therefore important that such assessments are based on all reliable and relevant scientific data, and that assessment principles and assumptions, such as expert judgment, are transparently applied. It is not possible nor desirable to completely eliminate expert judgment from the evaluation of (eco) toxicity studies. However, it is desirable to introduce measures that increase structure and transparency in the evaluation process so as to provide scientifically robust risk assessments that can be used for regulatory decision making. In this article we present results from workshop exercises with Nordic experts to illustrate how experts' evaluations regarding the reliability and relevance of (eco) toxicity studies for risk assessment may vary and discuss methods intended to promote structure and transparency in the evaluation process.

  • 361.
    Beronius, Anna
    et al.
    Stockholm University, Faculty of Science, Department of Applied Environmental Science (ITM).
    Hanberg, Annika
    Zilliacus, Johanna
    Rudén, Christina
    Stockholm University, Faculty of Science, Department of Applied Environmental Science (ITM).
    Bridging the gap between academic research and regulatory health risk assessment of Endocrine Disrupting Chemicals2014In: Current opinion in pharmacology (Print), ISSN 1471-4892, E-ISSN 1471-4973, Vol. 19, p. 99-104Article in journal (Refereed)
    Abstract [en]

    Regulatory risk assessment is traditionally based primarily on toxicity studies conducted according to standardized and internationally validated test guidelines. However, health risk assessment of endocrine disrupting chemicals (EDCs) is argued to rely on the efficient integration of findings from academic research. The aim of this review was to provide an overview of current developments to facilitate the use of academic research in regulatory risk assessment of chemicals and how certain aspects of study design and reporting are particularly important for the risk assessment process. By bridging the gap between academic research and regulatory health risk assessment of EDCs, scientific uncertainty in risk assessment conclusions can be reduced, allowing for better targeted policy decisions for chemical risk reduction.

  • 362. Beronius, Anna
    et al.
    Johansson, Niklas
    Rudén, Christina
    Stockholm University, Faculty of Science, Department of Applied Environmental Science (ITM).
    Hanberg, Annika
    The influence of study design and sex-differences on results from developmental neurotoxicity studies of bisphenol A, implications for toxicity testing2013In: Toxicology, ISSN 0300-483X, E-ISSN 1879-3185, Vol. 311, no 1-2, p. 13-26Article in journal (Refereed)
    Abstract [en]

    Developmental neurotoxicity (DNT) of bisphenol A (BPA) has been investigated in a large number of studies. However, there are discrepancies in the results reported between the studies. The aim of this study was to identify and analyze factors that may contribute to these differences and to assess whether there are sex-differences in the sensitivity of certain endpoints or tests used in DNT-studies. Forty-four DNT studies of BPA were identified from the open literature. Details about study design and results from each study, as well as the criteria for DNT testing according to the standardized OECD test guideline (TG) 426, were collected in a database. This enabled systematic and detailed comparisons between studies as well as to the criteria and recommendations stated in TG 426. Multivariate analyses were also used to investigate how different factors of the study design contributed to differences in study results. The analyses showed behavioral effects were often observed for endpoints that are not required according to OECD TG 426, such as anxiety-related, social and sexual behaviors, especially at very low doses and in female offspring. On the other hand relatively few studies observed any effects on motor activity, which is commonly used in screening for neurotoxic effects in regulatory testing. However, varied and to some extent seemingly contradictory results have been reported in these studies, especially for endpoints related to motor activity and anxiety and exploration. Many studies were also poorly reported, limiting these analyses. No strong conclusions could be drawn from the multivariate analyses. A few factors of study design, such as the size of the dose and number of dose levels used and the use of litter or individual pup as statistical unit seemed to have some influence on study results. In conclusion, this analysis suggests that DNT-studies conducted according to the standardized OECD TG 426 may overlook sensitive effects of BPA, and possibly other potential endocrine disruptors, especially in female offspring.

  • 363.
    Beronius, Anna
    et al.
    Stockholm University, Faculty of Science, Department of Applied Environmental Science (ITM). Karolinska Institute, Sweden.
    Molander, Linda
    Stockholm University, Faculty of Science, Department of Applied Environmental Science (ITM).
    Rudén, Christina
    Stockholm University, Faculty of Science, Department of Applied Environmental Science (ITM).
    Hanberg, Annika
    Facilitating the use of non-standard in vivo studies in health risk assessment of chemicals: a proposal to improve evaluation criteria and reporting2014In: Journal of Applied Toxicology, ISSN 0260-437X, E-ISSN 1099-1263, Vol. 34, no 6, p. 607-617Article in journal (Refereed)
    Abstract [en]

    To improve data availability in health risk assessment of chemicals and fill information gaps there is a need to facilitate the use of non-standard toxicity studies, i.e. studies not conducted according to any standardized toxicity test guidelines. The purpose of this work was to propose criteria and guidance for the evaluation of reliability and relevance of non-standard in vivo studies, which could be used to facilitate systematic and transparent evaluation of such studies for health risk assessment. Another aim was to propose user friendly guidance for reporting of non-standard studies intended to promote an improvement in reporting of studies that could be of use in risk assessment. Requirements and recommendations for the design and execution of in vivo toxicity studies were identified from The Organisation for Economic Co-operation and Development (OECD) test guidelines, and served as basis for the data evaluation criteria and reporting guidelines. Feedback was also collected from experts within the field of toxicity testing and risk assessment and used to construct a two-tiered framework for study evaluation, as well as refine the reporting guidelines. The proposed framework emphasizes the importance of study relevance and an important aspect is to not completely dismiss studies from health risk assessment based on very strict criteria for reliability. The suggested reporting guidelines provide researchers with a tool to fulfill reporting requirements as stated by regulatory agencies. Together, these resources provide an approach to include all relevant data that may fill information gaps and reduce scientific uncertainty in health risk assessment conclusions, and subsequently also in chemical policy decisions.

  • 364.
    Beronius, Anna
    et al.
    Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.
    Vandenberg, Laura N.
    Using systematic reviews for hazard and risk assessment of endocrine disrupting chemicals2016In: Reviews in endocrine and metabolic disorders (Print), ISSN 1389-9155, E-ISSN 1573-2606, Vol. 16, no 4, p. 273-287Article, review/survey (Refereed)
    Abstract [en]

    The possibility that endocrine disrupting chemicals (EDCs) in our environment contribute to hormonally related effects and diseases observed in human and wildlife populations has caused concern among decision makers and researchers alike. EDCs challenge principles traditionally applied in chemical risk assessment and the identification and assessment of these compounds has been a much debated topic during the last decade. State of the science reports and risk assessments of potential EDCs have been criticized for not using systematic and transparent approaches in the evaluation of evidence. In the fields of medicine and health care, systematic review methodologies have been developed and used to enable objectivity and transparency in the evaluation of scientific evidence for decision making. Lately, such approaches have also been promoted for use in the environmental health sciences and risk assessment of chemicals. Systematic review approaches could provide a tool for improving the evaluation of evidence for decision making regarding EDCs, e.g. by enabling systematic and transparent use of academic research data in this process. In this review we discuss the advantages and challenges of applying systematic review methodology in the identification and assessment of EDCs.

  • 365. Berthelsen, Hanne
    et al.
    Muhonen, Tuija
    Toivanen, Susanna
    Mälardalens högskola, Sverige.
    Vad händer med arbetsmiljön när man inför aktivitetsbaserade kontor inom akademin?2017In: Arbetsmarknad & Arbetsliv, ISSN 1400-9692, Vol. 23, no 3, p. 9-23Article in journal (Refereed)
    Abstract [sv]

    Aktivitetsbaserade kontor är fortfarande ovanliga för forskare och lärare inom akademin, men nu verkar flera lärosäten vara igång att införa den här typen av arbetsplatser. Det finns begränsat med kunskap om vad som händer vid flyttprocesser från egna rum till aktivitetsbaserade kontor i akademin och hur personalen upplever arbetsmiljön i denna typ av kontorsmiljöer. I den här artikeln redovisas resultat från en enkätundersökning före och efter flytt till aktivitetsbaserade kontor på en svensk högskola.

  • 366. Berthelsen, Hanne
    et al.
    Westerlund, Hugo
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Hakanen, Jari J.
    Kristensen, Tage S.
    It is not just about occupation, but also about where you work2017In: Community Dentistry and Oral Epidemiology, ISSN 0301-5661, E-ISSN 1600-0528, Vol. 45, no 4, p. 372-379Article in journal (Refereed)
    Abstract [en]

    Objectives: Dentistry is characterized by a meaningful but also stressful psychosocial working environment. Job satisfaction varies among staff working under different organizational forms. The aim of this study was to identify (i) to what extent crucial psychosocial work environment characteristics differ among occupations in general public dental clinics in Sweden, and (ii) how much of the variation within each occupation is attributable to the organizational level. Methods: All staff (N=1782) employed in four public dental organizations received an email with personal log-in to an electronic questionnaire based on the Copenhagen Psychosocial Questionnaire. After two reminders, a response rate of 75% was obtained. Responses from 880 nonmanagerial dentists, dental hygienists and dental nurses working in general practices were included in our analyses. Results: First, we compared the three dental occupations. We found that job demands, task resources (eg influence, possibilities for development and role clarity), strain symptoms and attitudes to work differed among occupations, dentists having the least favourable situation. Next, we compared the four organizations for each occupational group, separately. For dentists, a significant and relevant amount of variance (P<.05 and ICC >.05) was explained by the organizational level for 15 of 26 subscales, least pronounced for task resources. By contrast, for dental nurses and hygienists, the corresponding number was 2 subscales of 26. The psychosocial working environment of people working at the organization with the highest levels of strain indicators and the least positive work-related attitudes differed systematically from the organization with the most favourable profile, in particular regarding job demands and leadership aspects. Conclusion: In conclusion, the psychosocial working environment depended to a large degree on occupation and, for dentists in particular, also on their organizational affiliation. The findings suggest a potential for designing interventions at organizational level for improvements of the psychosocial working environment for dentists.

  • 367.
    Berthet, Pierre
    et al.
    Stockholm University, Faculty of Science, Numerical Analysis and Computer Science (NADA). Royal Institute of Technology, Sweden.
    Hellgren-Kotaleski, Jeanette
    Lansner, Anders
    Stockholm University, Faculty of Science, Numerical Analysis and Computer Science (NADA). Royal Institute of Technology, Sweden.
    Action selection performance of a reconfigurable basal ganglia inspired model with Hebbian-Bayesian Go- NoGo connectivity2012In: Frontiers in Behavioral Neuroscience, ISSN 1662-5153, E-ISSN 1662-5153, Vol. 6, article id 65Article in journal (Refereed)
    Abstract [en]

    Several studies have shown a strong involvement of the basal ganglia (BG) in action selection and dopamine dependent learning. The dopaminergic signal to striatum, the input stage of the BG, has been commonly described as coding a reward prediction error (RPE), i.e., the difference between the predicted and actual reward. The RPE has been hypothesized to be critical in the modulation of the synaptic plasticity in cortico-striatal synapses in the direct and indirect pathway. We developed an abstract computational model of the BG, with a dual pathway structure functionally corresponding to the direct and indirect pathways, and compared its behavior to biological data as well as other reinforcement learning models. The computations in our model are inspired by Bayesian inference, and the synaptic plasticity changes depend on a three factor Hebbian-Bayesian learning rule based on co-activation of pre- and post-synaptic units and on the value of the RPE. The model builds on a modified Actor-Critic architecture and implements the direct (Go) and the indirect(NoGo) pathway, as well as the reward prediction (RP) system, acting in a complementary fashion. We investigated the performance of the model system when different configurations of the Go, NoGo, and RP system were utilized, e.g., using only the Go, NoGo, or RP system, or combinations of those. Learning performance was investigated in several types of learning paradigms, such as learning-relearning, successive learning, stochastic learning, reversal learning and a two-choice task. The RPE and the activity of the model during learning were similar to monkey electrophysiological and behavioral data. Our results, however, show that there is not a unique best way to configure this BG model to handle well all the learning paradigms tested. We thus suggest that an agent might dynamically configure its action selection mode, possibly depending on task characteristics and also on how much time is available.

  • 368.
    Berthet, Pierre
    et al.
    Stockholm University, Faculty of Science, Numerical Analysis and Computer Science (NADA). Karolinska Institute, Sweden.
    Lindahl, Mikael
    Tully, Philip J.
    Hellgren-Kotaleski, Jeanette
    Lansner, Anders
    Stockholm University, Faculty of Science, Numerical Analysis and Computer Science (NADA). Karolinska Institute, Sweden.
    Functional Relevance of Different Basal Ganglia Pathways Investigated in a Spiking Model with Reward Dependent Plasticity2016In: Frontiers in Neural Circuits, ISSN 1662-5110, E-ISSN 1662-5110, Vol. 10, article id 53Article in journal (Refereed)
    Abstract [en]

    The brain enables animals to behaviorally adapt in order to survive in a complex and dynamic environment, but how reward-oriented behaviors are achieved and computed by its underlying neural circuitry is an open question. To address this concern, we have developed a spiking model of the basal ganglia (BG) that learns to dis-inhibit the action leading to a reward despite ongoing changes in the reward schedule. The architecture of the network features the two pathways commonly described in BG, the direct (denoted D1) and the indirect (denoted D2) pathway, as well as a loop involving striatum and the dopaminergic system. The activity of these dopaminergic neurons conveys the reward prediction error (RPE), which determines the magnitude of synaptic plasticity within the different pathways. All plastic connections implement a versatile four-factor learning rule derived from Bayesian inference that depends upon pre- and post-synaptic activity, receptor type, and dopamine level. Synaptic weight updates occur in the D1 or D2 pathways depending on the sign of the RPE, and an efference copy informs upstream nuclei about the action selected. We demonstrate successful performance of the system in a multiple-choice learning task with a transiently changing reward schedule. We simulate lesioning of the various pathways and show that a condition without the D2 pathway fares worse than one without D1. Additionally, we simulate the degeneration observed in Parkinson's disease (PD) by decreasing the number of dopaminergic neurons during learning. The results suggest that the D1 pathway impairment in PD might have been overlooked. Furthermore, an analysis of the alterations in the synaptic weights shows that using the absolute reward value instead of the RPE leads to a larger change in D1.

  • 369. Besga, A.
    et al.
    Cedazo-Minguez, A.
    Kåreholt, I.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Solomon, A.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Björkhem, I.
    Winblad, B.
    Leoni, V.
    Hooshmand, B.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Spulber, G.
    Gonzalez-Pinto, A.
    Kivipelto, M.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Wahlund, L. O.
    Differences in brain cholesterol metabolism and insulin in two subgroups of patients with different CSF biomarkers but similar white matter lesions suggest different pathogenic mechanisms2012In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 510, no 2, p. 121-126Article in journal (Refereed)
    Abstract [en]

    Investigate possible associations of white matter hyperintensities (WMHs) with the metabolism of cholesterol and insulin in two subgroups of patients with memory complaints and different CSF A beta 42 and CSF tau levels. 59 patients from the memory clinic at Karolinska Hospital were included. Degree of WMHs was rated using the ARWMC scale and the following biomarkers were measured in CSF and plasma: insulin, cholesterol, lanosterol, lathosterol, and oxidized cholesterol metabolites. The WMHs in CSF control-like group correlated with increased brain cholesterol synthesis and reduced efflux of oxysterols and insulin in CSF. In the CSF AD-like group, the WMHs correlated with increased peripheral cholesterol metabolism. Despite having similar appearance on FLAIR images, the pathogenic mechanisms of WMHS are likely to be different in the two groups investigated.

  • 370. Beskow, Catharina
    et al.
    Ågren-Cronqvist, Anna-Karin
    Lewensohn, Rolf
    Toma-Dasu, Iuliana
    Stockholm University, Faculty of Science, Department of Physics.
    Biological effective dose evaluation and assessment of rectal and bladder complications for cervical cancer treated with radiotherapy and surgery2012In: Journal of Contemporary Brachytherapy, ISSN 1689-832X, E-ISSN 2081-2841, Vol. 4, no 4, p. 205-212Article in journal (Refereed)
    Abstract [en]

    Purpose: This study aims to retrospectively evaluate dosimetric parameters calculated as biological effective dose in relation to outcome in patients with cervical cancer treated with various treatment approaches including radiotherapy, with and without surgery.

    Methods and Materials: Calculations of biological effective dose (BED) were performed on data from a retrospective analysis of 171 patients with cervical carcinoma stages IB-IIB treated with curative intent between January 1989 and December 1991. 43 patients were treated only with radiotherapy and 128 patients were treated with a combination of radiotherapy and surgery. External beam radiotherapy was delivered with 6-21 MV photons from linear accelerators. Brachytherapy was delivered either with a manual radium technique or with a remote afterloading technique. The treatment outcome was evaluated at 5 years.

    Results: The disease-specific survival rate was 87% for stage IB, 75% for stage IIA and 54% for stage IIB, while the overall survival rates were 84% for stage IB, 68% for stage IIA and 43% for stage IIB. Patients treated only with radiotherapy had a local control rate of 77% which was comparable to that for radiotherapy and surgery patients (78%). Late complications were recorded in 25 patients (15%). Among patients treated with radiotherapy and surgery, differences in radiation dose calculated as BED10 did not seem to influence survival. For patients treated with radiotherapy only, a higher BED10 was correlated to a higher overall survival (p=0.0075). The dose response parameters found based on biological effective dose calculations were D50=85.2 Gy10 and γ=1.62 for survival and D50=61.6 Gy10 and γ=0.92 for local control.

    Conclusions: The outcome correlates with biological effective dose for patients treated with radiation therapy alone, but not for patients treated with radiotherapy and surgery. No correlations were found between BED and late toxicity from bladder and rectum.

  • 371. Bestas, Burcu
    et al.
    Moreno, Pedro M. D.
    Blomberg, K. Emelie M.
    Mohammad, Dara K.
    Saleh, Amer F.
    Sutlu, Tolga
    Nordin, Joel Z.
    Guterstam, Peter
    Stockholm University, Faculty of Science, Department of Neurochemistry.
    Gustafsson, Manuela O.
    Kharazi, Shabnam
    Piatosa, Barbara
    Roberts, Thomas C.
    Behlke, Mark A.
    Wood, Matthew J. A.
    Gait, Michael J.
    Lundin, Karin E.
    EL Andaloussi, Samir
    Mansson, Robert
    Berglof, Anna
    Wengel, Jesper
    Smith, C. I. Edvard
    Splice-correcting oligonucleotides restore BTK function in X-linked agammaglobulinemia model2014In: Journal of Clinical Investigation, ISSN 0021-9738, E-ISSN 1558-8238, Vol. 124, no 9, p. 4067-4081Article in journal (Refereed)
    Abstract [en]

    X-linked agammaglobulinemia (XLA) is an inherited immunodeficiency that results from mutations within the gene encoding Bruton's tyrosine kinase (BTK). Many XLA-associated mutations affect splicing of BTK pre-mRNA and severely impair B cell development. Here, we assessed the potential of antisense, splice-correcting oligonucleotides (SCOs) targeting mutated BTKtranscripts for treating XLA. Both the SCO structural design and chemical properties were optimized using 2'-O-methyl, locked nucleic acid, or phosphorodiamidate morpholino backbones. In order to have access to an animal model of XLA, we engineered a transgenic mouse that harbors a BAC with an authentic, mutated, splice-defective human BTK gene. BTK transgenic mice were bred onto a Btk knockout background to avoid interference of the orthologous mouse protein. Using this model, we determined that BTK-specific SCOs are able to correct aberrantly spliced BTK in B lymphocytes, including pro-B cells. Correction of BTK mRNA restored expression of functional protein, as shown both by enhanced lymphocyte survival and reestablished BTK activation upon B cell receptor stimulation. Furthermore, SCO treatment corrected splicing and restored BTK expression in primary cells from patients with XLA. Together, our data demonstrate that SCOs can restore BTK function and that BTK-targeting SCOs have potential as personalized medicine in patients with XLA.

  • 372. Beziat, Vivien
    et al.
    Liu, Lisa L.
    Malmberg, Jenny-Ann
    Ivarsson, Martin A.
    Sohlberg, Ebba
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Björklund, Andreas T.
    Retiere, Christelle
    Sverremark-Ekström, Eva
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Traherne, James
    Ljungman, Per
    Schaffer, Marie
    Price, David A.
    Trowsdale, John
    Michaelsson, Jakob
    Ljunggren, Hans-Gustaf
    Malmberg, Karl-Johan
    NK cell responses to cytomegalovirus infection lead to stable imprints in the human KIR repertoire and involve activating KIRs2013In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 121, no 14, p. 2678-2688Article in journal (Refereed)
    Abstract [en]

    Human natural killer (NK) cells are functionally regulated by killer cell immunoglobulin-like receptors (KIRs) and their interactions with HLA class I molecules. As KIR expression in a given NK cell is genetically hard-wired, we hypothesized that KIR repertoire perturbations reflect expansions of unique NK-cell subsets and may be used to trace adaptation of the NK-cell compartment to virus infections. By determining the human KIR-ome at a single-cell level in more than 200 donors, we were able to analyze the magnitude of NK cell adaptation to virus infections in healthy individuals. Strikingly, infection with human cytomegalovirus (CMV), but not with other common herpesviruses, induced expansion and differentiation of KIR-expressing NK cells, visible as stable imprints in the repertoire. Education by inhibitory KIRs promoted the clonal-like expansion of NK cells, causing a bias for self-specific inhibitory KIRs. Furthermore, our data revealed a unique contribution of activating KIRs (KIR2DS4, KIR2DS2, or KIR3DS1), in addition to NKG2C, in the expansion of human NK cells. These results provide new insight into the diversity of KIR repertoire and its adaptation to virus infection, suggesting a role for both activating and inhibitory KIRs in immunity to CMV infection.

  • 373. Bhandage, A. K.
    et al.
    Hellgren, C.
    Jin, Z.
    Olafsson, Einar B.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Sundström-Poromaa, I.
    Birnir, B.
    Expression of GABA receptors subunits in peripheral blood mononuclear cells is gender dependent, altered in pregnancy and modified by mental health2015In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 213, no 3, p. 575-585Article in journal (Refereed)
    Abstract [en]

    AimThe concept of nerve-driven immunity recognizes a link between the nervous and the immune system. -aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the brain, and receptors activated by GABA can be expressed by immune cells. Here, we examined whether the expression of GABA receptors and chloride transporters in human peripheral blood mononuclear cells (PBMCs) was influenced by gender, pregnancy or mental health. MethodsWe used RT-qPCR to determine the mRNA expression level in PBMCs from men (n=16), non-pregnant women (n=19), healthy pregnant women (n=27) and depressed pregnant women (n=15). ResultsThe 2 subunit had the most prominent expression level of the GABA-A receptor subunits in all samples. The and 2 subunits were up-regulated by pregnancy, whereas the epsilon subunit was more frequently expressed in healthy pregnant women than non-pregnant women who, in turn, commonly expressed the 6 and the 2 subunits. The 1 and epsilon subunits expression was altered by depression in pregnant women. The GABA-B1 receptor was up-regulated by depression in pregnant women, while the transporters NKCC1 and KCC4 were down-regulated by pregnancy. The changes recorded in the mRNA expression levels imply participation of GABA receptors in establishing and maintaining tolerance in pregnancy. Importantly, the correlation of mental health with the expression of specific receptor subunits reveals a connection between the immune cells and the brain. Biomarkers for mental health may be identified in PBMCs. ConclusionThe results demonstrate the impact gender, pregnancy and mental health have on the expression of GABA receptors and chloride transporters expressed in human PBMCs.

  • 374. Bharadwaj, Prashant
    et al.
    Lundborg, Petter
    Rooth, Dan-Olof
    Stockholm University, Faculty of Social Sciences, The Swedish Institute for Social Research (SOFI).
    Birth Weight in the Long Run2018In: The Journal of human resources, ISSN 0022-166X, E-ISSN 1548-8004, Vol. 53, no 1, p. 189-231Article in journal (Refereed)
    Abstract [en]

    We study the effect of birth weight on long-run outcomes using data on Swedish twins born between 1926 and 1958 linked to administrative records spanning entire life-time labor market histories. We find that birth weight positively affects permanent income and income across large parts of the lifecycle. The timing of the birth weight–income relationship is in line with the role of birth weight in determining takeup of sickness benefits and morbidity. The effect of birth weight on labor market outcomes even for cohorts born 30 years apart are similar; for short run health outcomes, birth weight plays a decreasing role over time.

  • 375.
    Bhushan, Shashi
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Kuhn, Claus
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Berglund, Anna-Karin
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Roth, Christian
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Glaser, Elzbieta
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    The role of the N-terminal domain of chloroplast targeting peptides in organellar protein import and miss-sorting2006In: FEBS Letters, ISSN 0014-5793, E-ISSN 1873-3468, Vol. 580, no 16, p. 3966-3972Article in journal (Refereed)
    Abstract [en]

    We have analysed 385 mitochondrial and 567 chloroplastic signal sequences of proteins found in the organellar proteomes of Arabidopsis thaliana. Despite overall similarities, the first 16 residues of transit peptides differ remarkably. To test the hypothesis that the N-terminally truncated transit peptides would redirect chloroplastic precursor proteins to mitochondria, we studied import of the N-terminal deletion mutants of ELIP, PetC and Lhcb2.1. The results show that the deletion mutants were neither imported into chloroplasts nor miss-targeted to mitochondria in vitro and in vivo, showing that the entire transit peptide is necessary for correct targeting as well as miss-sorting.

  • 376.
    Bhushan, Shashi
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Pavlov, Pavel F
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Rudhe, Charlotta
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Glaser, Elzbieta
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    In vitro and in vivo methods to study protein import into plant mitochondria.2007In: Methods Mol Biol, ISSN 1064-3745, Vol. 390, p. 131-50Article in journal (Refereed)
    Abstract [en]

    Plant mitochondria contain about 1000 proteins, 90-99% of which in different plant species are nuclear encoded, synthesized on cytosolic polyribosomes, and imported into the organelle. Most of the nuclear-encoded proteins are synthesized as precursors containing an N-terminal extension called a presequence or targeting peptide that directs the protein to the mitochondria. Here we describe in vitro and in vivo methods to study mitochondrial protein import in plants. In vitro synthesized precursor proteins can be imported in vitro into isolated mitochondria (single organelle import). However, missorting of chloroplast precursors in vitro into isolated mitochondria has been observed. A novel dual import system for simultaneous import of proteins into isolated mitochondria and chloroplasts followed by reisolation of the organelles is superior over the single import system as it abolishes the mistargeting. Precursor proteins can also be imported into the mitochondria in vivo using an intact cellular system. In vivo approaches include import of transiently expressed fusion constructs containing a presequence or a full-length precursor protein fused to a reporter gene, most commonly the green fluorescence protein (GFP) in protoplasts or in an Agrobacterium-mediated system in intact tobacco leaves.

  • 377.
    Bielawski, Marcin
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Olofsson, Berit
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Efficient one-pot synthesis of bis(4-tert-butylphenyl)iodonium triflate2009In: Organic Syntheses, ISSN 0078-6209, Vol. 86, p. 308-314Article in journal (Refereed)
  • 378. Biffi, Annalisa
    et al.
    Scotti, Lorenza
    Rea, Federico
    Lucenteforte, Ersilia
    Chinellato, Alessandro
    Vetrano, Davide L.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Università Cattolica del Sacro Cuore, Italy.
    Vitale, Cristiana
    Agabiti, Nera
    Sultana, Janet
    Roberto, Giuseppe
    Mugelli, Alessandro
    Corrao, Giovanni
    Adherence to Antidepressants and Mortality in Elderly Patients with Cardiovascular Disease2018In: Clinical drug investigation, ISSN 1173-2563, E-ISSN 1179-1918, Vol. 38, no 7, p. 593-602Article in journal (Refereed)
    Abstract [en]

    Background and Objective

    Conflicting findings from studies evaluating the association between use of antidepressant drugs and mortality have been reported. We tested the hypothesis that better adherence to antidepressant therapy may reduce mortality.

    Methods

    The cohort included 29,845 individuals aged >= 65 years from several Italian health units who were newly treated with antidepressant drugs after hospital discharge with a diagnosis for cardiovascular disease during 2008-2010. These individuals were observed from the first prescription until the end of data availability (i.e. 2012-2014, depending on the local database). During this period, information on (1) prescription of antidepressants and other medications and (2) death from any cause (outcome) was recorded. Proportional hazards models were fitted to estimate the association between better adherence to antidepressants (defined as proportion of days covered > 75%) and outcome, by adjusting and stratifying for several covariates.

    Results

    Patients with better adherence to antidepressants had a reduced mortality of 9% (95% CI 3-14). Patients who did not use other medicaments during follow-up had reduced mortality associated with better adherence to antidepressants of 21% (- 1-38), 14% (7-20), 20% (13-26) and 13% (7-19) for no users of antihypertensive agents, lipid-lowering agents, other cardiovascular drugs and antidiabetics, respectively.

    Conclusions

    Better adherence to antidepressants is associated with reduced all-cause mortality, mainly in patients who did not use other pharmacological treatments. Behavioural changes to enhance adherence among the elderly with cardiovascular disease might offer important benefits in reducing their mortality.

  • 379. Bijlsma, Maarten J.
    et al.
    Tarkiainen, Lasse
    Myrskylä, Mikko
    Martikainen, Pekka
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS). Max Planck Institute for Demographic Research, Germany: University of Helsinki,, Finland.
    Unemployment and subsequent depression: A mediation analysis using the parametric G-formula2017In: Social Science and Medicine, ISSN 0277-9536, E-ISSN 1873-5347, Vol. 194, p. 142-150Article in journal (Refereed)
    Abstract [en]

    The effects of unemployment on depression are difficult to establish because of confounding and limited understanding of the mechanisms at the population level. In particular, due to longitudinal interdependencies between exposures, mediators and outcomes, intermediate confounding is an obstacle for mediation analyses. Using longitudinal Finnish register data on socio-economic characteristics and medication purchases, we extracted individuals who entered the labor market between ages 16 and 25 in the period 1996 to 2001 and followed them until the year 2007 (n = 42,172). With the parametric G-formula we estimated the population averaged effect on first antidepressant purchase of a simulated intervention which set all unemployed person years to employed. In the data, 74% of person-years were employed and 8% unemployed, the rest belonging to studying or other status. In the intervention scenario, employment rose to 85% and the hazard of first antidepressant purchase decreased by 7.6%. Of this reduction 61% was mediated, operating primarily through changes in income and household status, while mediation through other health conditions was negligible. These effects were negligible for women and particularly prominent among less educated men. By taking complex interdependencies into account in a framework of observed repeated measures data, we found that eradicating unemployment raises income levels, promotes family formation, and thereby reduces antidepressant consumption at the population-level.

  • 380.
    Bildtgård, Torbjörn
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Social Work.
    Öberg, Peter
    Time as a structuring condition behind new intimate relationships in later life2015In: Ageing & Society, ISSN 0144-686X, E-ISSN 1469-1779, Vol. 35, no 7, p. 1505-1528Article in journal (Refereed)
    Abstract [en]

    Although mobility in and out of intimate relationships has become more common in later life, it has been a neglected issue in social gerontology. In this article, we ask what characterises the formation of new intimate relationships in later life, and whether there are any specific conditions that separate these from relationships in earlier stages of the lifecourse. On the basis of qualitative interviews with 28 persons aged 63-91 who have established a new intimate heterosexual relationship after the age of 60 or who are dating singles, we argue that time constitutes such a central structuring condition. We discuss and theorise two aspects of time - post-(re) productive free time and remaining time - which have an important formative power on new late-in-life relationships. We argue that together these aspects form a central existential structure of ageing in many Western societies - the paradoxical condition of having lots of available free time but little time left in life - which, besides influencing new late-in-life relationships, might also be relevant to other aspects of and choices in later life.

  • 381. Bill-Axelsson, Anna
    et al.
    Holmberg, Lars
    Filen, F
    Ruutu, M
    Garmo, Hans
    Busch, Christer
    Nordling, S
    Hamberg, H
    Häggman, M
    Andersson, S-O
    Bratell, S
    Spångberg, A
    Palmgren, Juni
    Stockholm University, Faculty of Science, Department of Mathematics.
    Adami, Hans-Olov
    Johansson, Jan-Erik
    Radical Prostatectomy versus Wathful Waiting in Localized Prostate Cancer: The Scandinavian Prostate Cancer Group (SPCG-4) Randomized Trial2008In: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 100, p. 1144-1154Article in journal (Refereed)
  • 382. Binder, Zev A.
    et al.
    Haseley Thorne, Amy
    Bakas, Spyridon
    Wileyto, E. Paul
    Bilello, Michel
    Akbari, Hamed
    Rathore, Saima
    Ha, Sung Min
    Zhang, Logan
    Ferguson, Cole J.
    Dahiya, Sonika
    Bi, Wenya Linda
    Reardon, David A.
    Idbaih, Ahmed
    Felsberg, Joerg
    Hentschel, Bettina
    Weller, Michael
    Bagley, Stephen J.
    Morrissette, Jennifer J. D.
    Nasrallah, MacLean P.
    Ma, Jianhui
    Zanca, Ciro
    Scott, Andrew M.
    Orellana, Laura
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Davatzikos, Christos
    Furnari, Frank B.
    O'Rourke, Donald M.
    Epidermal Growth Factor Receptor Extracellular Domain Mutations in Glioblastoma Present Opportunities for Clinical Imaging and Therapeutic Development2018In: Cancer Cell, ISSN 1535-6108, E-ISSN 1878-3686, Vol. 34, no 1, p. 163-177Article in journal (Refereed)
    Abstract [en]

    We explored the clinical and pathological impact of epidermal growth factor receptor (EGFR) extracellular domain missense mutations. Retrospective assessment of 260 de novo glioblastoma patients revealed a significant reduction in overall survival of patients having tumors with EGFR mutations at alanine 289 (EGFR(A289D/T/V)). Quantitative multi-parametric magnetic resonance imaging analyses indicated increased tumor invasion for EGFR(A289D/T/V) mutants, corroborated in mice bearing intracranial tumors expressing EGFR(A289V) and dependent on ERK-mediated expression of matrix metalloproteinase-1. EGFR(A289V) tumor growth was attenuated with an antibody against a cryptic epitope, based on in silico simulation. The findings of this study indicate a highly invasive phenotype associated with the EGFR(A289V) mutation in glioblastoma, postulating EGFR(A289V) as a molecular marker for responsiveness to therapy with EGFR-targeting antibodies.

  • 383.
    Birse, Ryan Tyge
    Stockholm University, Faculty of Science, Department of Zoology.
    Tachykinin-related peptide signaling and its role in metabolic stress in Drosophila2006Doctoral thesis, monograph (Other academic)
    Abstract [en]

    Tachykinins (TKs) constitute a highly conserved family of multifunctional neuropeptides that are known to be involved in a multitude of functions in mammals. Peptides that are presumed ancestrally related to tachykinins, so called Tachykinin-related peptides (TKRP) have been identified in invertebrates.

    Little is known about the in vivo actions of TKRPs in invertebrates. Therefore, we decided to study the TKRP signaling in the Drosophila melanogaster. Drosophila has been shown to have a tachykinin system with multiple peptides encoded on a single gene (Tk) and two G-protein coupled receptors (GPCRs), designated DTKR and NKD. The two GPCRs were further characterized in this thesis with native DTKs.

    We raised several antibodies for immunocytochemical detection of DTKR and NKD to investigate the distribution of the two receptors. We found that the two GPCRs are differentially distributed and when combined cover all regions of the DTK distribution.

    To analyze receptor function in vivo we used the GAL4-UAS system to over express DTKR and NKD with different cell specific GAL4 drivers, likely to shed light on metabolic stress responses. We also tested the effect of a DTK RNA interference (Tk-KO) transgene, in, which levels of DTK transcript was decreased by up to 95%. These flies were tested for different parameters like trehalose and lipid levels, longevity, and locomotor activity levels at starvation. We found that the Tk-KO flies displayed a prolonged lifespan and no detectable decrease trehalose. We also showed that over expression of the two GPCRs elicits different responses depending on the cell type they are expressed in. Over expression of NKD in AKH producing cells is likely to cause a release of adipokinetic hormone (AKH) while DTKR appears to have an inhibitory action on release of Drosophila insulin-like peptides (DILPs) when expressed on DILP2 producing cells.

    It has been previously shown in the locust that TKRPs are released into the haemolymph from the midgut upon starvation. We therefore used Gal4s specifically directed to the two different cells types (principal and stellate cells) of the Malpighian tubules to drive DTKR and NKD. Only when expressing the DTKR receptor in the principal cells did we see an altered phenotype during nutritional and desiccative stress. We found that over expression of DTKR produced an abbreviated lifespan. We also tested the Tk-KO flies and found that they exhibited under desiccative stress. Finally, we expressed a DTKR-RNAi construct in the both Malpighian tubules cells type and found that in both cell types the receptor knockdown produced an extended lifespan compared to controls. These data suggests that since only substances in the circulation can activate receptors on the Malpighian tubules DTKs are likely to be released into the circulation upon starvation. In summary our data indicate that DTKs and the two GPCRs are involved in signalling during metabolic stress.

  • 384. Bjaastad, Jon Fauskanger
    et al.
    Haugland, Bente Storm Mowatt
    Fjermestad, Krister W.
    Torsheim, Torbjorn
    Havik, Odd E.
    Heiervang, Einar R.
    Öst, Lars-Goran
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Clinical psychology. Karolinska Institutet, Sweden.
    Competence and Adherence Scale for Cognitive Behavioral Therapy (CAS-CBT) for Anxiety Disorders in Youth: Psychometric Properties2016In: Psychological Assessment, ISSN 1040-3590, E-ISSN 1939-134X, Vol. 28, no 8, p. 908-916Article in journal (Refereed)
    Abstract [en]

    The aim of the present study was to evaluate the psychometric properties of the Competence and Adherence Scale for Cognitive Behavioral Therapy (CAS-CBT). The CAS-CBT is an 11-item scale developed to measure adherence and competence in cognitive-behavioral therapy (CBT) for anxiety disorders in youth. A total of 181 videotapes from the treatment sessions in a randomized controlled effectiveness trial (Wergeland et al., 2014) comprising youth (N = 182, M age = 11.5 years, SD = 2.1, range 8-15 years, 53% girls, 90.7% Caucasian) with mixed anxiety disorders were assessed with the CAS-CBT to investigate interitem correlations, internal consistency, and factor structure. Internal consistency was good (Cronbach's alpha = .87). Factor analysis suggested a 2-factor solution with Factor 1 representing CBT structure and session goals (explaining 46.9% of the variance) and Factor 2 representing process and relational skills (explaining 19.7% of the variance). The sum-score for adherence and competence was strongly intercorrelated, r = .79, p < .001. Novice raters (graduate psychology students) obtained satisfactory accuracy (ICC > .40, n = 10 videotapes) and also good to excellent interrater reliability when compared to expert raters (ICC = .83 for adherence and .64 for competence, n = 26 videotapes). High rater stability was also found (n = 15 videotapes). The findings suggest that the CAS-CBT is a reliable measure of adherence and competence in manualized CBT for anxiety disorders in youth. Further research is needed to investigate the validity of the scale and psychometric properties when used with other treatment programs, disorders and treatment formats.

  • 385. Bjerge, Bagga
    et al.
    Houborg, Esben
    Edman, Johan
    Stockholm University, Faculty of Social Sciences, Centre for Social Research on Alcohol and Drugs (SoRAD).
    Perälä, Riikka
    Concepts and policies directed at drug use i Denmark, Finland and Sweden2016In: Concepts of Addictive Behaviours across Time and Place / [ed] Matilda Hellman, Virginia Berridge, Karen Duke, Alex Mold, Oxford: Oxford University Press, 2016Chapter in book (Refereed)
    Abstract [en]

    The Nordic countries are often thought of in terms of social democratic welfare regimes with numerous shared cultural aspects. Based on research from Denmark, Finland, and Sweden, this chapter explores how historical developments, specific ways of constructing policies, and welfare institutions articulate specific conceptions of what drug-related issues are and how they should be managed in three seemingly very similar welfare states. The Nordic welfare states are often described as quite alike and fairly open and inclusive in their approach to welfare policies and concerns, but the chapter demonstrates that similar political systems adopt different policy responses to similar conditions. To explore the similarities and differences, we are inspired by the analytical concepts of policy space and political rationalities; we use this approach to provide an overview of drug policy history in the three countries and present a closer examination of the topics of sanctions against drug users, coercive treatment, and substitution treatment nationally as well as cross-nationally.

  • 386. Bjorklund, Geir
    et al.
    Stejskal, Vera
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Urbina, Mauricio A.
    Dadar, Maryam
    Chirumbolo, Salvatore
    Mutter, Joachim
    Metals and Parkinson's Disease: Mechanisms and Biochemical Processes2018In: Current Medicinal Chemistry, ISSN 0929-8673, E-ISSN 1875-533X, Vol. 25, no 19, p. 2198-2214Article, review/survey (Refereed)
    Abstract [en]

    Genetic background accounts for only 5 to 10% of the reported cases of Parkinson's disease (PD), while the remaining cases are of unknown etiology. It is believed that environmental factors may be involved in the causality of a large proportion of PD cases. Several PD genes are activated by xenobiotic exposure, and a link between pesticide exposure and PD has been demonstrated. Many epidemiological studies have shown an association between PD and exposure to metals such as mercury, lead, manganese, copper, iron, aluminum, bismuth, thallium, and zinc. This review explores the biological effects, the pathogenetic processes, genetic susceptibilities to metals as well as examining future strategies for PD treatment, such as chelation therapy.

  • 387. Björk, Christel
    et al.
    Nenonen, Hannah
    Giwercman, Aleksander
    Bergman, Åke
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Environmental Chemistry.
    Rylander, Lars
    Giwercman, Yvonne Lundberg
    Persistent organic pollutants have dose and CAG repeat length dependent effects on androgen receptor activity in vitro2011In: Reproductive Toxicology, ISSN 0890-6238, E-ISSN 1873-1708, Vol. 32, p. 293-297Article in journal (Refereed)
    Abstract [en]

    Recently, the effect of exposure to persistent organic pollutants (POPS) on sperm concentration was only seen in men with a short androgen receptor (AR) gene CAG repeat. In order to investigate whether these effects could be observed also in vitro, we tested the impact of 2,2’,4,4’,5,5’-hexachlorobiphenyl (CB-153) and 1,1-bis-(4-chlorophenyl)-2,2-dichloroethene (4,4’-DDE) on 5 alpha-dihydrotestosterone activated ARs containing 16,22 and 28 CAG repeats, respectively. Single exposure to 4,4’-DDE had the most pronounced effect on the AR activity containing 16 CAG repeats, whereas 28 CAG was the most sensitive variant when a mixture of the two compounds was added. Thus, our in vitro results have confirmed the in vivo data indicating a CAG repeat length dependent effect of endocrine disrupters on the AR activity.

  • 388. Björk, Tabita
    et al.
    Brus, Ole
    Osika, Walter
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Montgomery, Scott
    Laterality, hand control and scholastic performance: a British birth cohort study2012In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 2, no 2, p. e000314-Article in journal (Refereed)
    Abstract [en]

    Objectives: To use simple measures of laterality and hand control that can identify a greater risk of poorer scholastic ability, potentially signalling suboptimal hemispheric lateralisation.

    Design: Analysis of material from a birth cohort study.

    Setting: Members of the National Child Development Study, a British birth cohort study following people born in 1958.

    Participants: 10 612 children who undertook tests at age 11 years.

    Primary outcome measures: Teacher-administered tests of non-verbal general ability, verbal general ability, reading comprehension and mathematics. 

    Results Linear regression produced associations (and 95% CIs) with tests of verbal general ability, non-verbal general ability, reading comprehension and mathematics scores for the lowest third (compared with highest) of a left-hand control test involving picking up matches of −1.21 (−1.73 to −0.68; p<0.001), −0.72 (−1.14 to −0.29; p=0.001), −0.70 (−1.06 to −0.35; p<0.001) and −1.32 (−1.90 to −0.73; p<0.001). Among those in the lowest third of the right-hand control test score, mixed-handedness compared with right-handedness was associated with poorer scholastic performance, with regression coefficients (and 95% CIs; p values) of 1.90 (−3.01 to −0.80; p=0.001), −1.25 (−2.15 to −0.35; p=0.007), −1.28 (2.04 to −0.53; p=0.001) and −1.33 (−2.53 to −0.13; p=0.030). The estimates are for a point change in the scholastic test scores, after adjustment for sex, left-hand motor function and social class. Statistically significant associations with mixed-handedness were only observed for the lowest third of right-hand motor function.

    Conclusions Measures involving poorer left-hand motor function may represent useful markers of reduced cognitive function possibly reflecting suboptimal hemispheric lateralisation. Crude measures of laterality such as reported non-right-handedness may be more useful for research when combined with measures of motor function.                        

  • 389.
    Björkander, Sophia
    et al.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Hell, Lena
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Johansson, Maria A.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Mata Forsberg, Manuel
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Lasaviciute, Gintare
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Roos, Stefan
    Holmlund, Ulrika
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Sverremark-Ekström, Eva
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Staphylococcus aureus-derived factors induce IL-10, IFN-gamma and IL-17A-expressing FOXP3(+)CD161(+) T-helper cells in a partly monocyte-dependent manner2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 22083Article in journal (Refereed)
    Abstract [en]

    Staphylococcus aureus (S. aureus) is a human pathogen as well as a frequent colonizer of skin and mucosa. This bacterium potently activates conventional T-cells through superantigens and it is suggested to induce T-cell cytokine-production as well as to promote a regulatory phenotype in T-cells in order to avoid clearance. This study aimed to investigate how S. aureus impacts the production of regulatory and pro-inflammatory cytokines and the expression of CD161 and HELIOS by peripheral CD4(+)FOXP3(+) T-cells. Stimulation of PBMC with S. aureus 161:2-cell free supernatant (CFS) induced expression of IL-10, IFN-gamma and IL-17A in FOXP3(+) cells. Further, CD161 and HELIOS separated the FOXP3(+) cells into four distinct populations regarding cytokine-expression. Monocyte-depletion decreased S. aureus 161:2-induced activation of FOXP3(+) cells while pre-stimulation of purified monocytes with S. aureus 161:2-CFS and subsequent co-culture with autologous monocyte-depleted PBMC was sufficient to mediate activation of FOXP3(+) cells. Together, these data show that S. aureus potently induces FOXP3(+) cells and promotes a diverse phenotype with expression of regulatory and pro-inflammatory cytokines connected to increased CD161-expression. This could indicate potent regulation or a contribution of FOXP3(+) cells to inflammation and repression of immune-suppression upon encounter with S. aureus.

  • 390. Björkenstam, C.
    et al.
    Bjorkenstam, E.
    Ljung, R.
    Vinnerljung, Bo
    Stockholm University, Faculty of Social Sciences, Department of Social Work.
    Tuvblad, C.
    Suicidal behavior among delinquent former child welfare clients2013In: European Child and Adolescent Psychiatry, ISSN 1018-8827, E-ISSN 1435-165X, Vol. 22, no 6, p. 349-355Article in journal (Refereed)
    Abstract [en]

    Child welfare clients represent a high-risk group for delinquency and adult criminality, but also for future suicidal behavior. We examine associations between delinquency and suicidal behavior in a national child welfare population. This register-based cohort study is based on data for all Swedish former child welfare clients born between 1972 and 1981 that experienced interventions before their adolescent years. We followed 27,228 individuals from age 20 years until 31 December 2006. Juvenile delinquency was defined as being convicted of at least one crime between age 15 and 19. The risk of suicidal behavior was calculated as incidence rate ratios (IRRs). Fifteen percent of the women and 40 % of the men had at least one conviction between the age 15 and 19. The adjusted risk of suicidal behavior among women with five or more convictions was 3.5 (95 % CI 2.0-6.2); corresponding IRR for men was 3.9 (95 % CI 3.1-4.9). Child welfare experience-specifically of out-of-home care-in combination with delinquency is a potent risk factor for suicidal behavior among young adults. However, we cannot exclude that some of this association is an epiphenomenon of uncontrolled confounders, such as impulsivity or severity of psychiatric disease. Despite this caveat, results should be disseminated to practitioners in the health and correction services.

  • 391. Björkenstam, C.
    et al.
    Björkenstam, E.
    Hjern, Anders
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS). Karolinska Institutet, Sweden.
    Boden, R.
    Reutfors, J.
    Suicide in first episode psychosis: A nationwide cohort study2014In: Schizophrenia Research, ISSN 0920-9964, E-ISSN 1573-2509, Vol. 157, no 1-3, p. 1-7Article in journal (Refereed)
    Abstract [en]

    Background: Relatively little is known about suicide in diagnostic subtypes of first episode psychosis (FEP). Our aim was to assess suicide rates and potential risk factors for suicide in FEP. Methods: This is a national register-based cohort study of patients born in 1973-1978 in Sweden and who were hospitalized with a FEP between ages 15 and 30 years (n = 2819). The patients were followed from date of discharge until death, emigration, or 31st of December 2008. The suicide rates for six diagnostic subtypes of FEP were calculated. Suicide incidence rate ratios (IRRs) were calculated to evaluate the association between suicide and psychiatric, familial, social, and demographic factors. Results: In total 121 patients died by suicide. The overall suicide rate was 4.3 (95% confidence interval [CI] 3.5-5.0) per 1000 person-years. The highest suicide rates were found in depressive disorder with psychotic symptoms and in delusional disorder. In an adjustedmodel, the strongest risk factors for suicide were self-harm (IRR 2.7, CI 1.7-4.4) or a conviction for violent crime (IRR 2.0, CI 1.3-3.2). Also having a first-degree relative with a schizophrenia/bipolar diagnosis (IRR 2.1, CI 1.2-3.6) or substance use disorder (IRR 2.0, CI 1.2-3.2) were significant risk factors for suicide. Conclusions: Impulsive behavior such as self-harm as well as having a family history of severe mental disorder or substance use are important risk factors for suicide in FEP.

  • 392. Björkenstam, C.
    et al.
    Weitoft, G.R.
    Hjern, Anders
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS).
    Nordstrom, P.
    Hallqvist, J.
    Ljung, R.
    School grades, parental education and suicide: a national register-based cohort study2010In: Journal of Epidemiology and Community Health, ISSN 0143-005X, E-ISSN 1470-2738Article in journal (Refereed)
    Abstract [en]

    Background To investigate whether school performance is a risk factor for suicide death later in life and, if so, to what extent this is explained by intergenerational effects of parental education.

    Methods This population-based cohort study comprises national birth cohorts between 1972 and 1981 in Sweden. We followed 898 342 students, graduating between 1988 and 1997 from the 9 years of compulsory school, equivalent to junior high school, until 31 December 2006, generating 11 148 758 person-years and 1490 suicides. Final school grades, in six categories, and risk of suicide were analysed with Poisson regression.

    Results The incidence rate ratio (RR) for suicide death for students with the lowest grades was 4.57 (95% CI 2.82 to 7.40) for men and 2.67 (1.42 to 5.01) for women compared to those with highest grades after adjustment for a number of sociodemographic and parental morbidity variables, such as year of graduation, parental education, lone parenthood, household receiving social welfare or disability pension, place of schooling, adoption, maternal age and parent's mental illness. Students with grades in the middle categories had RRs in between. These relationships were not modified by parental education.

    Conclusions The strong association between low school grades and suicide in youth and young adulthood emphasises the importance of both primary and secondary prevention in schools.

  • 393.
    Björkenstam, Charlotte
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Sociology. University of California, USA; Karolinska Institutet, Sweden .
    Andersson, Gunnar
    Stockholm University, Faculty of Social Sciences, Department of Sociology.
    Dalman, Christina
    Cochran, Susan
    Kosidou, Kyriaki
    Suicide in married couples in Sweden: Is the risk greater in same-sex couples?2016In: European Journal of Epidemiology, ISSN 0393-2990, E-ISSN 1573-7284, Vol. 31, no 7, p. 685-690Article in journal (Refereed)
    Abstract [en]

    Minority sexual orientation is a predictor of suicide ideation and attempts, though its association with suicide mortality is less clear. We capitalize on Sweden's extensively linked databases, to investigate whether, among married individuals, same-sex marriage is associated with suicide. Using a population-based register design, we analyzed suicide risk among same-sex married women and men (n = 6456), as compared to different-sex married women and men (n = 1181723) in Sweden. We selected all newly partnered or married individuals in the intervening time between 1/1/1996 and 12/31/2009 and followed them with regard to suicide until 12/31/2011. Multivariate Poisson regression was used to calculate adjusted incidence risk ratios (IRR) with 95 % confidence intervals (CI). The risk of suicide was higher among same-sex married individuals as compared to different-sex married individuals (IRR 2.7, 95 % CI 1.5-4.8), after adjustment for time at risk and socioeconomic confounding. Sex-stratified analyses showed a tentatively elevated risk for same-sex married women (IRR 2.5, 95 % CI 0.8-7.7) as compared to different-sex married women. Among same-sex married men the suicide risk was nearly three-fold greater as compared to different-sex married (IRR 2.895 % CI 1.5-5.5). This holds true also after adjustment for HIV status. Even in a country with a comparatively tolerant climate regarding homosexuality such as Sweden, same-sex married individuals evidence a higher risk for suicide than other married individuals.

  • 394.
    Björkenstam, Charlotte
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Sociology. University of California, USA; Karolinska Institutet, Sweden.
    Björkenstam, Emma
    Andersson, Gunnar
    Stockholm University, Faculty of Social Sciences, Department of Sociology.
    Cochran, Susan
    Kosidou, Kyriaki
    Anxiety and Depression Among Sexual Minority Women and Men in Sweden: Is the Risk Equally Spread Within the Sexual Minority Population?2017In: Journal of Sexual Medicine, ISSN 1743-6095, E-ISSN 1743-6109, Vol. 14, no 3, p. 396-403Article in journal (Refereed)
    Abstract [en]

    Introduction

    Sexual minority individuals have a higher risk of anxiety and depression compared with heterosexuals. However, whether the higher risk is spread equally across the sexual minority population is not clear.

    Aim

    To investigate the association between sexual orientation and self-reported current anxiety and a history of diagnosis of depression, paying particular attention to possible subgroup differences in risks within the sexual minority population, stratified by sex and to examine participants' history of medical care for anxiety disorders and depression.

    Methods

    We conducted a population-based study of 874 lesbians and gays, 841 bisexuals, and 67,980 heterosexuals recruited in 2010 in Stockholm County. Data were obtained from self-administered surveys that were linked to nationwide registers. Main Outcome Measures: By using logistic regression, we compared risks of current anxiety, histories of diagnosed depression, and register-based medical care for anxiety and/or depression in lesbian and gay, bisexual, and heterosexual individuals.

    Results

    Bisexual women and gay men were more likely to report anxiety compared with their heterosexual peers. Bisexual individuals and gay men also were more likely to report a past diagnosis of depression. All sexual minority groups had an increased risk of having used medical care for anxiety and depression compared with heterosexuals, with bisexual women having the highest risk.

    Conclusion

    Bisexual women appear to be a particularly vulnerable sexual minority group. Advocating for nondiscrimination and protections for lesbian, gay, and bisexual people is a logical extension of the effort to lower the prevalence of mental illness.

  • 395.
    Björkenstam, Charlotte
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Sociology. Karolinska Institutet, Sweden; University of California, USA.
    Ekselius, Lisa
    Berlin, Marie
    Stockholm University, Faculty of Social Sciences, Department of Social Work. National Board of Health and Welfare, Sweden.
    Gerdin, Bengt
    Björkenstam, Emma
    Suicide risk and suicide method in patients with personality disorders2016In: Journal of Psychiatric Research, ISSN 0022-3956, E-ISSN 1879-1379, Vol. 83, p. 29-36Article in journal (Refereed)
    Abstract [en]

    Objective: The influence of psychopathology on suicide method has revealed different distributions among different psychiatric disorders. However, evidence is still scarce. We hypothesized that having a diagnosis of personality disorder (PD) affect the suicide method, and that different PD clusters would influence the suicide method in different ways. In addition, we hypothesized that the presence of psychiatric and somatic co-morbidity also affects the suicide method. Method: We examined 25,217 individuals aged 15-64 who had been hospitalized in Sweden with a main diagnosis of PD the years 1987-2013 (N = 25,217). The patients were followed from the date of first discharge until death or until the end of the follow-up period, i.e. December 31, 2013, for a total of 323,508.8 person-years, with a mean follow up time of 11.7 years. The SMR, i.e. the ratio between the observed number of suicides and the expected number of suicides, was used as a measure of risk. Results: Overall PD, different PD-clusters, and comorbidity influenced the suicide method. Hanging evidenced highest SMR in female PD patients (SMR 34.2 (95% CI: 29.3-39.8)), as compared to non-PD patients and jumping among male PD patients (SMR 24.8 (95% CI: 18.3-33.6)), as compared to non PD-patients. Furthermore, the elevated suicide risk was related to both psychiatric and somatic comorbidity. Conclusion: The increased suicide risk was unevenly distributed with respect to suicide method and type of PD. However, these differences were only moderate and greatly overshadowed by the overall excess suicide risk in having PD. Any attempt from society to decrease the suicide rate in persons with PD must take these characteristics into account.

  • 396.
    Björkenstam, Charlotte
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Sociology. Karolinska Institutet, Sweden; University of California, USA.
    Kosidou, Kyriaki
    Björkenstam, Emma
    Childhood adversity and risk of suicide: cohort study of 548 721 adolescents and young adults in Sweden2017In: BMJ. British Medical Journal, E-ISSN 1756-1833, Vol. 357, article id j1334Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE To examine the relation between childhood adversity, the role of school performance, and childhood psychopathology and the risk of suicide. DESIGN Cohort study of register based indicators of childhood adversity (at ages 0-14) including death in the family (suicide analysed separately), parental substance abuse, parental psychiatric disorder, substantial parental criminality, parental separation/single parent household, receipt of public assistance, and residential instability. SETTING Swedish medical birth register and various Swedish population based registers. PARTICIPANTS 548 721 individuals born 1987-91. MAIN OUTCOME MEASURES Estimates of suicide risk at ages 15-24 calculated as incidence rate ratios adjusted for time at risk and confounders. Results Adjusted incidence rate ratios for the relation between childhood adversity and suicide during adolescence and young adulthood ranged from 1.6 (95% confidence interval 1.1 to 2.4) for residential instability to 2.9 (1.4 to 5.9) for suicide in the family. There was a dose-response relation between accumulating childhood adversity and risk: 1.1 (0.9 to 1.4) for those exposed to one adversity and 1.9 (1.4 to 2.5) and 2.6 (1.9 to 3.4) for those exposed to two and three or more adversities, respectively. The association with increased risk of suicide remained even after adjustment for school performance and childhood psychopathology. CONCLUSION Childhood adversity is a risk factor for suicide in adolescence and young adulthood, particularly accumulated adversity. These results emphasise the importance of understanding the social mechanisms of suicide and the need for effective interventions early in life, aiming to alleviate the risk in disadvantaged children.

  • 397.
    Björkenstam, Charlotte
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Sociology. Karolinska Institutet, Sweden; University of California, USA.
    Kosidou, Kyriaki
    Björkenstam, Emma
    Dalman, Christina
    Andersson, Gunnar
    Stockholm University, Faculty of Social Sciences, Department of Sociology.
    Cochran, Susan
    Self-reported suicide ideation and attempts, and medical care for intentional self-harm in lesbians, gays and bisexuals in Sweden2016In: Journal of Epidemiology and Community Health, ISSN 0143-005X, E-ISSN 1470-2738, Vol. 70, no 9, p. 895-901Article in journal (Refereed)
    Abstract [en]

    Background Minority sexual orientation is a robust risk indicator for self-reported suicidal ideation and attempts. However, little is known about patterns of medical care for intentional self-harm in this vulnerable population. We investigate sexual orientation-related differences in self-reported lifetime suicide symptoms and medical care for intentional self-harm between 1969 and 2010, including age at initial treatment and recurrence. Methods We used data from the Stockholm Public Health Cohort, a population-based sample of 874 lesbians/gays, 841 bisexuals and 67980 heterosexuals, whose self-administered surveys have been linked to nationwide registers. Estimates of risk for medical care were calculated as incidence rate ratios (IRR) with 95% CIs. Results Both suicidal ideation and attempts were more commonly reported by lesbian/gay and bisexual (LGB) individuals. Adjusting for risk-time and confounding, lesbians (IRR 3.8, 95% CI 2.7 to 5.4) and bisexual women (IRR 5.4, 95% CI 4.4 to 6.6) experienced elevated risk for medical care for intentional self-harm, as compared to heterosexual women. Gay men evidenced higher risk (IRR 2.1, 95% CI 1.3 to 3.4) as compared to heterosexual men. Recurrent medical care was more frequent in LGB individuals, especially in bisexual women and gay men. Lesbian and bisexual women were also younger than heterosexual women when they first received medical care for intentional self-harm. Conclusions Positive histories of suicidal ideation, attempts and medical care for intentional self-harm, including higher levels of recurrence, are more prevalent among LGB individuals in contrast to heterosexuals. Lesbian/bisexual women evidence an earlier age of onset of treatment. Tailored prevention efforts are urgently needed.

  • 398. Björkenstam, E.
    et al.
    Björkenstam, C.
    Hjern, Anders
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS).
    Reutfors, J.
    Bodén, R.
    A five year diagnostic follow-up of 1840 patients after a first episode non-schizophrenia and non-affective psychosis2013In: Schizophrenia Research, ISSN 0920-9964, E-ISSN 1573-2509, Vol. 150, no 1, p. 205-210Article in journal (Refereed)
    Abstract [en]

    Objective

    It is not clear which patients with a first psychotic episode will develop schizophrenia. We performed a diagnostic follow-up of patients treated for a first time non-affective, non-schizophrenia psychosis and explored potential predictors of a subsequent schizophrenia or schizoaffective diagnosis.

    Methods

    This register-based cohort study comprises individuals born between 1973 and 1978 in Sweden, with a first hospital-treated psychosis excluding schizophrenia, schizoaffective disorder, bipolar disorder and depressive disorder with psychotic symptoms (n = 1840). The patients were followed for five years regarding subsequent diagnoses. Psychiatric, social, family history of psychiatric illness, premorbid intellectual level, head injuries and obstetrical complications were investigated by logistic regression as predictors of schizophrenia or schizoaffective diagnosis.

    Results

    During the follow-up, 18% were diagnosed with schizophrenia or schizoaffective disorder, 5% were diagnosed with bipolar disorder, whereas 29% were not re-admitted to a psychiatric clinic. Patients with a first-degree relative hospitalized for schizophrenia and/or bipolar disorder had an increased risk of subsequent diagnosis for schizophrenia or schizoaffective disorder (odds ratio 1.9 and 95% confidence interval 1.1 to 3.0)), whereas previous severe criminality was associated with a decreased risk (odds ratio 0.5, 95% confidence interval 0.3–0.8).

    Conclusion

    Diagnostic outcome was diverse after a first non-schizophrenia and non-affective psychosis. Family history of severe mental illness and no previous conviction for severe criminality were the strongest risk factors for a future schizophrenia or schizoaffective diagnosis.

  • 399. Björkenstam, Emma
    et al.
    Burström, Bo
    Brännström, Lars
    Stockholm University, Faculty of Social Sciences, Department of Social Work.
    Vinnerljung, Bo
    Stockholm University, Faculty of Social Sciences, Department of Social Work.
    Björkenstam, Charlotte
    Pebley, Anne R.
    Cumulative exposure to childhood stressors and subsequent psychological distress. An analysis of US panel data2015In: Social Science and Medicine, ISSN 0277-9536, E-ISSN 1873-5347, Vol. 142, p. 109-117Article in journal (Refereed)
    Abstract [en]

    Research has shown that childhood stress increases the risk of poor mental health later in life. We examined the effect of childhood stressors on psychological distress and self-reported depression in young adulthood. Data were obtained from the Child Development Supplement (CDS) to the national Panel Study of Income Dynamics (PSID), a survey of US families that incorporates data from parents and their children. In 2005 and 2007, the Panel Study of Income Dynamics was supplemented with two waves of Transition into Adulthood (TA) data drawn from a national sample of young adults, 18-23 years old. This study included data from participants in the CDS and the TA (n = 2128), children aged 4-13 at baseline. Data on current psychological distress was used as an outcome variable in logistic regressions, calculated as odds ratios (OR) with 95% confidence intervals (CI). Latent Class Analyses were used to identify clusters based on the different childhood stressors. Associations were observed between cumulative exposure to childhood stressors and both psychological distress and self-reported depression. Individuals being exposed to three or more stressors had the highest risk (crude OR for psychological distress: 2.49 (95% Cl: 1.16-5.33), crude OR for self-reported depression: 2.07 (95% CI: 1.15-3.71). However, a large part was explained by adolescent depressive symptoms. Findings support the long-term negative impact of cumulative exposure to childhood stress on psychological distress. The important role of adolescent depression in this association also needs to be taken into consideration in future studies.

  • 400. Björkenstam, Emma
    et al.
    Burström, Bo
    Vinnerljung, Bo
    Stockholm University, Faculty of Social Sciences, Department of Social Work.
    Kosidou, Kyriaki
    Childhood adversity and psychiatric disorder in young adulthood: An analysis of 107,704 Swedes2016In: Journal of Psychiatric Research, ISSN 0022-3956, E-ISSN 1879-1379, Vol. 77, p. 67-75Article in journal (Refereed)
    Abstract [en]

    Childhood adversity (CA) is associated with increased risks of psychiatric disorder in young adulthood, but details in this association are less known. We aimed to explore the association of a range of CA indicators with psychiatric disorder in young adulthood, and the impact of age at exposure, disorder type and accumulation of indicators. We capitalized on Sweden's extensive and high-quality registers and analyzed a cohort of all Swedes (N = 107,704) born in Stockholm County 1987-1991. Adversities included familial death, parental substance misuse and psychiatric disorder, parental criminality, parental separation, public assistance recipiency and residential instability. Age at exposure was categorized as: 0-6.9 years (infancy and early childhood), 7-11.9 years (middle childhood), and 12-14 years (early adolescence). Psychiatric disorders after age 15 were defined from ICD codes through registers. Risks were calculated as Hazard Ratios (HR) with 95% confidence intervals (CI). Results showed that exposure to at least one CA was associated with an increased risk of psychiatric disorder (HR 1.4, 95% CI: 1.3-1.4). Risks were increased for mood, anxiety, and psychotic disorders and ADHD but not for eating disorders. The risk varied with type of disorder but was similar for all exposure periods. Individuals with multiple (3+) CAs had a two-fold risk of psychiatric disorder (HR 2.0, 95% CI: 1.9-2.1). In conclusion, our findings support the long-term negative impact of CA on mental health, regardless of developmental period of exposure. Given that experience of CA is common, efforts should be put to alleviate the burden of childhood adversities for children, particularly among the most disadvantaged.

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