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  • 1.
    Ahrén-Moonga, Jennie
    et al.
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS).
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    von Blixten, Nils
    Rönnelid, Johan
    Holmgren, Sven
    af Klinteberg, Britt
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS). Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Levels of tumour necrosis factor-alpha and interleukin-6 in severely ill patients with eating disorders2011In: Neuropsychobiology, ISSN 0302-282X, E-ISSN 1423-0224, Vol. 63, no 1, p. 8-14Article in journal (Refereed)
    Abstract [en]

    Background: The underlying pathophysiology of eating disorders (ED) is dependent on complex interactions between psychological, biological and social factors. The purpose of the present study was to examine a possible increase in cytokines indicating inflammation, as measured by tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in ED patients, and to explore possible relationships between cytokines and self-reported personality traits. Methods: Female patients with severe ED (n = 26) were recruited consecutively from an inpatient clinic and were compared to age-matched healthy females (n = 12). Commercial ELISA tests developed for the measurement of serum levels of TNF-α and IL-6 were employed. Personality traits were measured using Karolinska Scales of Personality. Results: The patient group displayed increased levels of the cytokine TNF-α and a tendency towards increased IL-6 levels. Spearman's rank correlation coefficient was used to examine possible relationships between levels of cytokines and personality traits. The results showed that IL-6 levels were positively related to both somatic and psychic anxiety and to aggression scales, such as irritability and suspicion. Increased levels of TNF-α, in turn, were significantly correlated with high scores on the depression-related anxiety scale Inhibition of Aggression. However, increased levels of cytokines in the ED group did not seem to be mainly associated with symptoms of depression. Conclusion: We cannot rule out the possibility that comorbid conditions in the group contribute to the higher cytokine values. Further studies need to explore the possible influence of cytokines on the severity of ED and whether this might be mediated or moderated by specific personality traits.

  • 2. Albrecht, Daniel S.
    et al.
    Forsberg, Anton
    Sandstrom, Angelica
    Bergan, Courtney
    Kadetoff, Diana
    Protsenko, Ekaterina
    Lampa, Jon
    Lee, Yvonne C.
    Hoglund, Caroline Olgart
    Catana, Ciprian
    Cervenka, Simon
    Akeju, Oluwaseun
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden; Karolinska University Hospital, Sweden.
    Cohen, George
    Halldin, Christer
    Taylor, Norman
    Kim, Minhae
    Hooker, Jacob M.
    Edwards, Robert R.
    Napadow, Vitaly
    Kosek, Eva
    Loggia, Marco L.
    Brain glial activation in fibromyalgia - A multi-site positron emission tomography investigation2019In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 75, p. 72-83Article in journal (Refereed)
    Abstract [en]

    Fibromyalgia (FM) is a poorly understood chronic condition characterized by widespread musculoskeletal pain, fatigue, and cognitive difficulties. While mounting evidence suggests a role for neuroinflammation, no study has directly provided evidence of brain glial activation in FM. In this study, we conducted a Positron Emission Tomography (PET) study using [C-11]PBR28, which binds to the translocator protein (TSPO), a protein upregulated in activated microglia and astrocytes. To enhance statistical power and generalizability, we combined datasets collected independently at two separate institutions (Massachusetts General Hospital [MGH] and Karolinska Institutet [KI]). In an attempt to disentangle the contributions of different glial cell types to FM, a smaller sample was scanned at KI with [C-11]-L-deprenyl-D2 PET, thought to primarily reflect astrocytic (but not microglial) signal. Thirty-one FM patients and 27 healthy controls (HC) were examined using [C-11]PBR28 PET. 11 FM patients and 11 HC were scanned using [C-11]-L-deprenyl-D2 PET. Standardized uptake values normalized by occipital cortex signal (SUVR) and distribution volume (V-T) were computed from the [C-11]PBR28 data. [C-11]-L-deprenyl-D2 was quantified using lambda k(3). PET imaging metrics were compared across groups, and when differing across groups, against clinical variables. Compared to HC, FM patients demonstrated widespread cortical elevations, and no decreases, in [C-11]PBR28 ITT and SUVR, most pronounced in the medial and lateral walls of the frontal and parietal lobes. No regions showed significant group differences in [C-11]-L-deprenyl-Ds signal, including those demonstrating elevated [C-11] PBR28 signal in patients (p's >= 0.53, uncorrected). The elevations in [C-11]PBR28 V-T and SUVR were correlated both spatially (i.e., were observed in overlapping regions) and, in several areas, also in terms of magnitude. In exploratory, uncorrected analyses, higher subjective ratings of fatigue in FM patients were associated with higher [C-11] PBR28 SUVR in the anterior and posterior middle cingulate cortices (p's < 0.03). SUVR was not significantly associated with any other clinical variable. Our work provides the first in vivo evidence supporting a role for glial activation in FM pathophysiology. Given that the elevations in [C-11]PBR28 signal were not also accompanied by increased [C-11]-deprenyl-D2 signal, our data suggests that microglia, but not astrocytes, may be driving the TSPO elevation in these regions. Although [C-11]-L-deprenyl-D2 signal was not found to be increased in FM patients, larger studies are needed to further assess the role of possible astrocytic contributions in FM. Overall, our data support glial modulation as a potential therapeutic strategy for FM.

  • 3.
    Andreasson, Anna
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Karshikoff, Bianka
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Lidberg, Lisa
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Åkerstedt, Torbjörn
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Ingvar, Martin
    Hoglund, Caroline Olgart
    Axelsson, John
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    The effect of a transient immune activation on subjective health perception in two placebo controlled randomised experiments2019In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, no 3, article id e0212313Article in journal (Refereed)
    Abstract [en]

    Background Patient-reported outcomes predict mortality and play increasingly important roles in care, but factors that modify central measures such as health ratings have been little investigated. Building on designated immune-to-brain pathways, we aimed to determine how a short-term induced inflammation response impacts self-reported health status. Methods Lipopolysaccharide injections were used to provoke acute systemic inflammatory responses in healthy men and women and were compared to placebo in two double-blind randomized experiments. In Experiment 1, 8 individuals (mean 24 years; SD = 3.7) received lipopolysaccharide 0.8 ng/kg once and placebo once in a cross-over design, and in Experiment 2, 52 individuals received either lipopolysaccharide 0.6 ng/kg or placebo once (28.6 years; SD = 7.1). Main outcomes were perceived health (general and current), sickness behaviour (like fatigue, pain and negative affect), and plasma interleukin-6, interleukin-8 and tumour necrosis factor-alpha, before and after injection. Results Compared to placebo, lipopolysaccharide lead to a deterioration in both self-rated general (Experiment 1, b = 1.88 for 0.8 ng/kg) and current health (Experiment 1 b = -3.00; and Experiment 2 b = -1.79) 1.5h after injection (p's<0.01), effects that remained after 4.5 to 5 hours (p's<0.05). The effect on current health in Experiment 2 was mediated by increased inflammation and sickness behaviour in response to lipopolysaccharide injection (beta = -0.28, p = 0.01). Conclusion Health is drastically re-evaluated during inflammatory activation. The findings are consistent with notions that inflammation forms part of health-relevant interoceptive computations of bodily state, and hint at one mechanism as to why subjective health predicts longevity.

  • 4.
    Andreasson, Anna N.
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Schiller, Helena
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Kecklund, Göran
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Contemplate your symptoms and re-evaluate your health2015In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 49, p. e38-e39Article in journal (Refereed)
    Abstract [en]

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

  • 5.
    Andreasson, Anna N.
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Wicksell, B.
    Karshikoff, B.
    Lodin, K.
    Axelsson, John
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Olgart Höglund, C.
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Development and preliminary validation of the Sickness Questionnaire (SicknessQ)2013In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 32, article id e14Article in journal (Refereed)
    Abstract [en]

    The lack of questionnaires to measure subjective feelings of being sick made us develope the Sickness Questionnaire (SicknessQ) for assessment of sickness behavior in people. The objective of the present investigation was to test its internal consistency, criteria validity, and sensitivity to capture the sickness response in an experimental setting. An initial pool of items was developed based on previous research. The statistical properties of SicknessQ was assessed in 172 men and women primary care patients with acute complaints and involved three steps: (1) principal component analyses to reduce the number of items and to identify latent factor structures, (2) tests of internal consistencies of subscales, and (3) hierarchical regression analyses to test criteria validity of the subscales. Subsequently, sensitivity to change was tested in a placebo controlled experiment in which 31 blinded healthy men and women were injected with endotoxin (LPS) to provoke sickness behavior. Principal components analysis suggested a 3-factor solution with a total of 11 items measuring fatigue (5 items), pain (4 items) and emotion (2 items). The total scale as well as each of the three separate factors were significantly changed 90 min after endotoxin injection as compared to baseline (p’s < .01). In all, the new 11-item SicknessQ is highly sensitive to a mild systemic inflammation. Further studies are planned to test its usefulness and prognostic value in clinical settings.

  • 6.
    Andreasson, Anna Nixon
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet.
    Szulkin, Robert
    Undén, Anna-Lena
    von Essen, Jan
    Nilsson, Lars-Göran
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet.
    Inflammation and positive affect are associated with subjective health in women of the general population2013In: Journal of Health Psychology, ISSN 1359-1053, E-ISSN 1461-7277, Vol. 18, no 3, p. 311-320Article in journal (Refereed)
    Abstract [en]

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

  • 7.
    Andreasson, Anna
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden; Macquarie University, Australia.
    Schiller, Helena
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Åkerstedt, Torbjörn
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Berntson, Erik
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Work and organizational psychology.
    Kecklund, Göran
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Brief report: Contemplate your symptoms and re-evaluate your health. A study on working adults2019In: Journal of Health Psychology, ISSN 1359-1053, E-ISSN 1461-7277, Vol. 24, no 11, p. 1562-1567Article in journal (Refereed)
    Abstract [en]

    We investigated whether self-ratings of health are affected by a symptom rating. A diary including a one-item self-rating of health ("pre-self-rated health"; 1 = excellent, 7 = very poor), a subsequent 26-item rating of symptoms, and thereafter a second (identical) health rating ("post-self-rated health") was completed by 820 persons 21 times. Self-rated health worsened significantly ( p < .0001) after the symptom rating, from 2.72 pre-self-rated health (95% confidence interval: 2.70-2.74) to 2.77 post-self-rated health (95% confidence interval: 2.75-2.79) and more so in persons who reported more symptoms ( b = .058, p < .05). The results support the notion that subjective health perception is influenced by attending to symptoms, especially so in persons with a high symptom burden.

  • 8.
    Andreasson, Anna
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Wicksell, Rikard K.
    Lodin, Karin
    Karshikoff, Bianka
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Axelsson, John
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    A global measure of sickness behaviour: Development of the Sickness Questionnaire2018In: Journal of Health Psychology, ISSN 1359-1053, E-ISSN 1461-7277, Vol. 23, no 11, p. 1452-1463Article in journal (Refereed)
    Abstract [en]

    Symptoms after inflammatory activation, so-called sickness behaviour, overlap with trans-diagnostic complaints. As no self-report questionnaire to assess sickness behaviour exists, we aimed to develop such an instrument, the Sickness Questionnaire. Items responsive to experimentally induced inflammatory activation (randomized double-blind study endotoxin (0.6 ng/kg) versus placebo, n = 52) were selected and the statistical properties were examined in 172 primary care patients. A principal component analysis indicated a one-factor solution (Cronbach's alpha = .86). This 10-item scale correlated with depression ( β = .41, p < .001), anxiety ( β = .36, p < .001), self-rated health ( β = .28, p < .001) and a single item of feeling sick ( β = .55, p < .001). The results support the adequacy of Sickness Questionnaire as a brief assessment instrument of perceived sickness behaviour.

  • 9.
    Arnberg, Filip K.
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Uppsala University, Sweden.
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Morey, Jennifer N.
    Segerström, Suzanne C.
    Self-rated health and interleukin-6: Longitudinal relationships in older adults2016In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 54, p. 226-232Article in journal (Refereed)
    Abstract [en]

    Background: Both self-rated health (SRH) and inflammation are implicated in chronic diseases and premature mortality. Better SRH is associated with lower proinflammatory cytokines, but there is little evidence about whether this relationship is more stable or dynamic.

    Objective: To study the between- and within-person associations between SRH and IL-6.

    Methods: Older adults (N=131; Mage=75years) rated their health and provided blood samples for analysis of IL-6 at separate occasions every 6months over a period up to 5years. Age, sex, BMI, neuroticism, and statin use were examined as covariates in multilevel models.

    Results: In bivariate models, better SRH, lower BMI, younger age, and female sex correlated with lower IL-6. In multilevel models, stable SRH (between-person differences; p<.001) but not dynamic SRH (within-person changes; p=.93) correlated with IL-6. The stable relationship persisted with demographic and health covariates in the model.

    Conclusions: Better stable SRH but not dynamic SRH was robustly associated with lower IL-6 among older adults, lending support to previous cross-sectional findings on the relation between inflammatory markers and SRH. The findings suggest that trait-like mechanisms, rather than changes over a time scale of 6-month waves, govern this association. To further investigate the mechanisms behind the SRH-IL-6 association, studies with different measurement frequencies, higher within-person variability, and experimental approaches are warranted.

  • 10.
    Axelsson, John
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Lasselin, Julie
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Man flu is related to health communication rather than symptoms and suffering2018In: BMJ. British Medical Journal, E-ISSN 1756-1833, Vol. 360, article id k450Article in journal (Other academic)
  • 11.
    Axelsson, John
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Karshikoff, B.
    Hedman, E.
    Is health anxiety related to disease avoidance?2015In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 49, article id e47Article in journal (Refereed)
  • 12.
    Axelsson, John
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Rehman, Javaid-ur
    Åkerstedt, Torbjörn
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Ekman, Rolf
    Miller, Gregory E.
    Höglund, Caroline Olgart
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska institutet, Sweden.
    Effects of Sustained Sleep Restriction on Mitogen-Stimulated Cytokines, Chemokines and T Helper 1/ T Helper 2 Balance in Humans2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 12, article id e82291Article in journal (Refereed)
    Abstract [en]

    Background: Recent studies suggest that acute sleep deprivation disrupts cellular immune responses by shifting T helper (Th) cell activity towards a Th2 cytokine profile. Since little is known about more long-term effects, we investigated how five days of sleep restriction would affect pro-inflammatory, chemotactic, Th1- and Th2 cytokine secretion. Methods: Nine healthy males participated in an experimental sleep protocol with two baseline sleep-wake cycles (sleep 23.00 - 07.00 h) followed by 5 days with restricted sleep (03.00 - 07.00 h). On the second baseline day and on the fifth day with restricted sleep, samples were drawn every third hour for determination of cytokines/chemokines (tumor necrosis factor alpha (TNF-alpha), interleukin (IL) -1 beta, IL-2, IL-4 and monocyte chemoattractant protein-1 (MCP-1)) after in vitro stimulation of whole blood samples with the mitogen phytohemagglutinin (PHA). Also leukocyte numbers, mononuclear cells and cortisol were analysed. Results: 5-days of sleep restriction affected PHA-induced immune responses in several ways. There was a general decrease of IL-2 production (p<.05). A shift in Th1/Th2 cytokine balance was also evident, as determined by a decrease in IL2/IL4 ratio. No other main effects of restricted sleep were shown. Two significant interactions showed that restricted sleep resulted in increased TNF-alpha and MCP-1 in the late evening and early night hours (p's<.05). In addition, all variables varied across the 24 h day. Conclusions: 5-days of sleep restriction is characterized by a shift towards Th2 activity (i.e. lower 1L-2/IL-4 ratio) which is similar to the effects of acute sleep deprivation and psychological stress. This may have implications for people suffering from conditions characterized by excessive Th2 activity like in allergic disease, such as asthma, for whom restricted sleep could have negative consequences.

  • 13. Axelsson, John
    et al.
    Sundelin, Tina
    Karolinska Institutet, Sweden.
    Ingre, Michael
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Van Someren, Eus J. W.
    Olsson, Andreas
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Beauty sleep: experimental study on the perceived health and attractiveness of sleep deprived people2010In: BMJ. British Medical Journal, E-ISSN 1756-1833, Vol. 341, article id c6614Article in journal (Refereed)
    Abstract [en]

    Our findings show that sleep deprived people appear less healthy, less attractive, and more tired compared with when they are well rested. This suggests that humans are sensitive to sleep related facial cues, with potential implications for social and clinical judgments and behaviour. Studies are warranted for understanding how these effects may affect clinical decision making and can add knowledge with direct implications in a medical context.

  • 14.
    Axelsson, John
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Sundelin, Tina
    Lasselin, Julie
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden; Universitätsklinikum Essen, Germany.
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    How can we improve identification of contagious individuals? Factors influencing sickness detection2018In: Proceedings of the Royal Society of London. Biological Sciences, ISSN 0962-8452, E-ISSN 1471-2954, Vol. 285, no 1889Article in journal (Refereed)
  • 15. Enblom, Anna
    et al.
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Hammar, Mats
    Johnsson, Anna
    Onelöv, Erik
    Ingvar, Martin
    Steineck, Gunnar
    Börjeson, Sussanne
    Getting the grip on nonspecific treatment effects: emesis in patients randomized to acupuncture or sham compared to patients receiving standard care2011In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, no 3, p. e14766-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: It is not known whether or not delivering acupuncture triggers mechanisms cited as placebo and if acupuncture or sham reduces radiotherapy-induced emesis more than standard care.

    METHODOLOGY/PRINCIPAL FINDINGS: Cancer patients receiving radiotherapy over abdominal/pelvic regions were randomized to verum (penetrating) acupuncture (n = 109; 99 provided data) in the alleged antiemetic acupuncture point PC6 or sham acupuncture (n = 106; 101 provided data) performed with a telescopic non-penetrating needle at a sham point 2-3 times/week during the whole radiotherapy period. The acupuncture cohort was compared to a reference cohort receiving standard care (n = 62; 62 provided data). The occurrence of emesis in each group was compared after a mean dose of 27 Gray. Nausea and vomiting were experienced during the preceding week by 37 and 8% in the verum acupuncture group, 38 and 7% in the sham acupuncture group and 63 and 15% in the standard care group, respectively. The lower occurrence of nausea in the acupuncture cohort (verum and sham) compared to patients receiving standard care (37% versus 63%, relative risk (RR) 0.6, 95 % confidence interval (CI) 0.5-0.8) was also true after adjustment for potential confounding factors for nausea (RR 0.8, CI 0.6 to 0.9). Nausea intensity was lower in the acupuncture cohort (78% no nausea, 13% a little, 8% moderate, 1% much) compared to the standard care cohort (52% no nausea, 32% a little, 15% moderate, 2% much) (p = 0.002). The acupuncture cohort expected antiemetic effects from their treatment (95%). Patients who expected nausea had increased risk for nausea compared to patients who expected low risk for nausea (RR 1.6; Cl 1.2-2.4).

    CONCLUSIONS/SIGNIFICANCE: Patients treated with verum or sham acupuncture experienced less nausea and vomiting compared to patients receiving standard care, possibly through a general care effect or due to the high level of patient expectancy.

    TRIAL REGISTRATION: ClinicalTrials.gov NCT00621660.

  • 16. Fang, Fang
    et al.
    Olgart Höglund, Caroline
    Arck, Petra
    Lundholm, Cecilia
    Långström, Niklas
    Lichtenstein, Paul
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Almqvist, Catarina
    Maternal bereavement and childhood asthma-analyses in two large samples of Swedish children2011In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, no 11, p. e27202-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Prenatal factors such as prenatal psychological stress might influence the development of childhood asthma.

    METHODOLOGY AND PRINCIPAL FINDINGS: We assessed the association between maternal bereavement shortly before and during pregnancy, as a proxy for prenatal stress, and the risk of childhood asthma in the offspring, based on two samples of children 1-4 (n = 426 334) and 7-12 (n = 493 813) years assembled from the Swedish Medical Birth Register. Exposure was maternal bereavement of a close relative from one year before pregnancy to child birth. Asthma event was defined by a hospital contact for asthma or at least two dispenses of inhaled corticosteroids or montelukast. In the younger sample we calculated hazards ratios (HRs) of a first-ever asthma event using Cox models and in the older sample odds ratio (ORs) of an asthma attack during 12 months using logistic regression. Compared to unexposed boys, exposed boys seemed to have a weakly higher risk of first-ever asthma event at 1-4 years (HR: 1.09; 95% confidence interval [CI]: 0.98, 1.22) as well as an asthma attack during 12 months at 7-12 years (OR: 1.10; 95% CI: 0.96, 1.24). No association was suggested for girls. Boys exposed during the second trimester had a significantly higher risk of asthma event at 1-4 years (HR: 1.55; 95% CI: 1.19, 2.02) and asthma attack at 7-12 years if the bereavement was an older child (OR: 1.58; 95% CI: 1.11, 2.25). The associations tended to be stronger if the bereavement was due to a traumatic death compared to natural death, but the difference was not statistically significant.

    CONCLUSIONS/SIGNIFICANCE: Our results showed some evidence for a positive association between prenatal stress and childhood asthma among boys but not girls.

  • 17. Fondell, Elinor
    et al.
    Axelsson, John
    Franck, Kristina
    Ploner, Alexander
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Bälter, Katarina
    Gaines, Hans
    Short natural sleep is associated with higher T cell and lower NK cell activities2011In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 25, no 7, p. 1367-1375Article in journal (Refereed)
    Abstract [en]

    Short sleep duration increases the risk of several diseases, possibly involving compromised immune function. However, most previous studies are based on experimentally induced sleep deprivation, and only a few have studied natural variations in sleep duration. Thus our aim was to study how natural variations in sleep duration affect immune function. In total, 36 healthy men and women, aged 20-54, donated blood; 29 on three consecutive mornings, and seven on one morning. Each morning, participants self-reported sleep duration the night prior to blood draw. General sleep patterns, physical activity and stress were also assessed. A flow-cytometric assay was used to measure natural killer cell activity (NKCA), T cell function (in response to PHA, influenza, and SEA+B), and B cell function (in response to PWM) per volume whole blood. Short sleep duration prior to blood draw (<7h) was associated with 49% higher PHA-induced T cell function (95% CI 7/109%) and 30% lower NKCA compared with normal prior sleep (7-9h) (95% CI -46/-8%). In addition, high perceived stress was associated with 39% higher PHA-induced T cell function (95% CI 0/94%). High general physical activity was associated with 47% increased numbers of B cells and 28% increased numbers of T cells, but not with immune function. Our results suggest strong relationships between short sleep duration and T- and NK-cell functions. The stability of the findings as well as the clinical consequences of the link between short sleep and immune function should be explored in future studies.

  • 18. Fondell, Elinor
    et al.
    Lagerros, Ylva Trolle
    Sundberg, Carl Johan
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Bälter, Olle
    Rothman, Kenneth J.
    Bälter, Katarina
    Physical Activity, Stress, and Self-Reported Upper Respiratory Tract Infection2011In: Medicine & Science in Sports & Exercise, ISSN 0195-9131, E-ISSN 1530-0315, Vol. 43, no 2, p. 272-279Article in journal (Refereed)
    Abstract [en]

    PURPOSE:: Upper respiratory tract infection (URTI) is the most common reason for seeking primary care in many countries. Still, little is known about potential strategies to reduce susceptibility. We investigated the relationships between physical activity level, perceived stress, and incidence of self-reported URTI. METHODS:: We conducted a population-based prospective cohort study of 1509 Swedish men and women aged 20-60 yr with a follow-up period of 4 months. We used a Web-based questionnaire to assess disease status and lifestyle factors at the start of the study. We assessed physical activity and inactivity as total MET-hours (MET task) per day and perceived stress by the 14-item Perceived Stress Scale. Participants were contacted every 3 wk via e-mail to assess incidence of URTI. They reported a total of 1181 occurrences of URTI. We used Poisson regression models to control for age, sex, and other potential confounding factors. RESULTS:: We found that high levels of physical activity (≥55 MET·h·d) were associated with an 18% reduced risk (incidence rate ratio (IRR) = 0.82, 95% confidence interval (CI) = 0.69-0.98) of self-reporting URTI compared with low levels of physical activity (<45 MET·h·d). This association was stronger among those reporting high levels of stress (IRR = 0.58, 95% CI = 0.43-0.78), especially among men (IRR = 0.37, 95% CI = 0.24-0.59), but absent in the group with low levels of stress. CONCLUSIONS:: We found that high physical activity was associated with a lower risk of contracting URTI for both men and women. In addition, we found that highly stressed people, particularly men, appear to benefit more from physical activity than those with lower stress levels.

  • 19. Forsberg, A.
    et al.
    Lampa, J.
    Estelius, J.
    Cervenka, S.
    Farde, L.
    Halldin, C.
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Höglund, Olgart C.
    Kosek, E.
    Disease activity in rheumatoid arthritis is inversely related to cerebral TSPO binding assessed by [C-11]PBR28 positron emission tomography2019In: Journal of Neuroimmunology, ISSN 0165-5728, E-ISSN 1872-8421, Vol. 334, article id UNSP 577000Article in journal (Refereed)
    Abstract [en]

    Reumatoid Arthritis (RA) is an autoimmune disorder characterized by peripheral joint inflammation. Recently, an engagement of the brain immune system has been proposed. The aim with the current investigation was to study the glial cell activation marker translocator protein (TSPO) in a well characterized cohort of RA patients and to relate it to disease activity, peripheral markers of inflammation and autonomic activity. Fifteen RA patients and fifteen healthy controls matched for age, sex and TSPO genotype (rs6971) were included in the study. TSPO was measured using Positron emission tomography (PET) and the radioligand [C-11] PBR28. The outcome measure was total distribution volume (V-T) estimated using Logan graphical analysis, with grey matter (GM) as the primary region of interest. Additional regions of interest analyses as well as voxel-wise analyses were also performed. Clinical evaluation of disease activity, symptom assessments, serum analyses of cytokines and heart rate variability (HRV) analysis of 24 h ambulatory ECG were performed in all subjects. There were no statistically significant group differences in TSPO binding, either when using the primary outcome V-T or when normalizing V-T to the lateral occipital cortex (p > 0.05). RA patients had numerically lower V-T values than healthy controls (Cohen's D for GM = -0.21). In the RA group, there was a strong negative correlation between [C-11]PBR28 V-T in GM and disease activity (DAS28)(r = -0.745, p = 0.002, corrected for rs6971 genotype). Higher serum levels of IFN gamma and TNF-alpha were found in RA patients compared to controls (p < 0.05) and several measures of autonomic activity showed significant differences between RA and controls (p < 0.05). However, no associations between markers of systemic inflammation or autonomic activity and cerebral TSPO binding were found. In conclusion, no statistically significant group differences in TSPO binding as measured with [C-11]PBR28 PET were detected. Within the RA group, lower cerebral TSPO binding was associated with higher disease activity, suggesting that cerebral TSPO expression may be related to disease modifying mechanisms in RA. In light of the earlier confirmed neuro-immune features of RA, these results warrant further investigations regarding neuro-immune joint-to-CNS signalling to open up for potentially new treatment strategies.

  • 20. Fransson, Emma
    et al.
    Dubicke, Aurelija
    Bystrom, Birgitta
    Ekman-Ordeberg, Gunvor
    Hjelmstedt, Anna
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Negative emotions and cytokines in maternal and cord serum at preterm birth2012In: American Journal of Reproductive Immunology and Microbiology, ISSN 8755-8920, Vol. 67, no 6, p. 506-514Article in journal (Refereed)
    Abstract [en]

    Problem This study investigates whether affectivity differs between mothers delivering preterm and term and whether maternal and umbilical cord serum cytokines differ between these groups. Further, whether there are associations between mothers emotions and maternal and cord cytokines at preterm and term birth. Method of study Twenty-seven mothers delivering preterm and 37 mothers delivering at term reported positive/negative affect and previous depressive symptoms during pregnancy. Blood samples from mothers in labor and cord samples (23 preterm and 33 term) were analyzed for cytokines. Results Maternal IL-8 was lower at preterm delivery compared with term. In the preterm group only, associations were found between negative emotions and maternal IL-6, IL-8 and cord IL-6, IL-8, IL-10, IL-13, and IL-18. Conclusion The findings indicate associations in preterm delivery between negative emotions and both maternal and neonate immune activity. Future studies should investigate whether such associations are part of the etiology of preterm delivery.

  • 21. Frimanson, L.
    et al.
    Anderzén, I.
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Frequency of prolonged social-evaluative threat and cytokine activity: A field experiment2013Conference paper (Refereed)
  • 22.
    Gerhardsson, Andreas
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Work and organizational psychology.
    Fischer, Håkan
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Biological psychology.
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Kecklund, Göran
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Axelsson, John
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Åkerstedt, Torbjörn
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Schwarz, Johanna
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Emotional working memory in older adults after total sleep deprivation2017In: Sleep Medicine, ISSN 1389-9457, E-ISSN 1878-5506, Vol. 40, no Suppl. 1, p. e110-e110Article in journal (Refereed)
    Abstract [en]

    Introduction: Even though the occurrence of sleep problems increases with age, few studies have focused on the cognitive effects of acute sleep deprivation in elderly. Most previous research indicate that, compared to young, older adults show less impairment in e.g. attention after sleep deprivation. However, little is known of whether the same pattern holds for higher cognitive functions. In addition, while old age is usually related to a general decrease in working memory abilities, performance on working memory tasks may differ depending on the emotional valence of the stimuli, where positive stimuli seem to be beneficial for working memory performance in older adults. The aim of the present study was to investigate the effect of sleep deprivation on emotional working memory in older adults using two levels of working memory load.

    Materials and methods: A healthy sample of 48 old adults (MAge=66.69 years, SDAge=3.44 years) was randomized into a total sleep deprivation group (TSD; n=24) or a sleep control group (SC; n=24). They performed a working memory task (n-back) containing positive, negative and neutral pictures in a low (1-back) and a high (3-back) working memory load condition. Performance was measured as Accuracy (d'), Omissions and Reaction Time (RT).

    Results: For the d' and Omissions we performed two separate 2x2x3 (sleep, working memory load, valence) repeated measures analyses of variance (rmANOVA). For the RTs, we applied a mixed-effects model. For both d' and RT we found no effect of sleep deprivation (Ps > .05). For valence, we found main effects on both d' (F1,46 = 5.56, P=.005) and RT (F1,95.7 = 4.84, P=.01). d' did not differ for positive and neutral pictures, but was in both cases significantly better than for negative pictures. RTs were significantly faster for positive pictures. However, a working memory loadvalence interaction (F1,95.7 = 4.50, P=.01) further revealed an effect of valence in the low, but not in the high load condition. In the low load condition, RTs were faster for positive than for neutral pictures and faster for neutral than for negative pictures. There was no significant effect of Omissions.

    Conclusions: Our results showed that emotional working memory performance was not significantly affected by one night of sleep deprivation in older adults, which contrast what we found in a sample of young adults from the same project. In line with previous research, our results indicate a beneficial effect of positive stimuli on working memory in older adults. This effect was present in both groups and most pronounced for reaction times in the condition with a lower cognitive demand. We can conclude that, among older adults, the working memory performance is not impaired by sleep deprivation and that the benefits of positive stimuli on working memory seem intact. These findings contribute to a better understanding of older adults' cognitive functioning after sleep deprivation.

  • 23.
    Gerhardsson, Andreas
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Psychology. Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Fischer, Håkan
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Kecklund, Göran
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Axelsson, John
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Åkerstedt, Torbjörn
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Schwarz, Johanna
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Positivity Effect and Working Memory Performance Remains Intact in Older Adults After Sleep Deprivation2019In: Frontiers in Psychology, ISSN 1664-1078, E-ISSN 1664-1078, Vol. 10, article id 605Article in journal (Refereed)
    Abstract [en]

    Background: Older adults perform better in tasks which include positive stimuli, referred to as the positivity effect. However, recent research suggests that the positivity effect could be attenuated when additional challenges such as stress or cognitive demands are introduced. Moreover, it is well established that older adults are relatively resilient to many of the adverse effects of sleep deprivation. Our aim was to investigate if the positivity effect in older adults is affected by one night of total sleep deprivation using an emotional working memory task.

    Methods: A healthy sample of 48 older adults (60-72 years) was either sleep deprived for one night (n = 24) or had a normal night's sleep (n = 24). They performed an emotional working memory n-back (n = 1 and 3) task containing positive, negative and neutral pictures.

    Results: Performance in terms of accuracy and reaction times was best for positive stimuli and worst for negative stimuli. This positivity effect was not altered by sleep deprivation. Results also showed that, despite significantly increased sleepiness, there was no effect of sleep deprivation on working memory performance. A working memory load x valence interaction on the reaction times revealed that the beneficial effect of positive stimuli was only present in the 1-back condition.

    Conclusion: While the positivity effect and general working memory abilities in older adults are intact after one night of sleep deprivation, increased cognitive demand attenuates the positivity effect on working memory speed.

  • 24.
    Gerhardsson, Andreas
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Åkerstedt, Torbjörn
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Axelsson, John
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Fischer, Håkan
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Biological psychology.
    Kecklund, Göran
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Schwarz, Johanna
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    The effect of sleep loss on emotional working memory2016In: Abstracts, 2016, Vol. 25(S1), p. 17-18Conference paper (Other academic)
    Abstract [en]

    Objectives: Emotional stimuli differently affect working memory (WM) performance. As sleep deprivation has a known impact on both emotion and WM our aim was to investigate how one night without sleep affects emotional WM performance. Methods: Healthy subjects (n = 56; age 18–30 years) were randomized to a total sleep deprivation (TSD) or a rested control (RC) condition. Subjects rated their affective state and performed a 1 and a 3-back WM task consisting of neutral, positive and negative pictures at 3 pm or 6 pm (balanced) the day after sleep manipulation. Accuracy (d’) and target response time (RT) were used as outcomes. Results: In the TSD condition, subjects rated themselves as less positive (P = 0.006) but not more negative than in the RC condition. In the WM task, TSD had a detrimental effect on accuracy (P = 0.03) regardless of difficulty. Moreover, accuracy was higher in the 1-back than in the 3-back (P < 0.001) and higher for neutral compared to both negative and positive stimuli (Ps < 0.05). RT was faster for positive compared to negative and neutral stimuli (Ps < 0.05). The latter effect was particularly pronounced in the TSD condition as shown by a condition*valence interaction (P < 0.03). Conclusions: One night of total sleep loss impaired emotional WM accuracy. Noticeable, RT was faster for positive stimuli compared to negative and neutral stimuli. This effect was particularly pronounced after sleep loss. This suggests that sleep loss strengthens the opposing effects of positive and negative stimuli on WM performance, possibly due to increased emotion reactivity.

  • 25.
    Gerhardsson, Andreas
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Work and organizational psychology. Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Åkerstedt, Torbjörn
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Axelsson, John
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Fischer, Håkan
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Biological psychology.
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Schwarz, Johanna
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Effect of sleep deprivation on emotional working memory2019In: Journal of Sleep Research, ISSN 0962-1105, E-ISSN 1365-2869, Vol. 28, no 1, article id e12744Article in journal (Refereed)
    Abstract [en]

    The emotional dysregulation and impaired working memory found after sleep loss can have severe implications for our daily functioning. Considering the intertwined relationship between emotion and cognition in stimuli processing, there could be further implications of sleep deprivation in high‐complex emotional situations. Although studied separately, this interaction between emotion and cognitive processes has been neglected in sleep research. The aim of the present study was to investigate the effect of 1 night of sleep deprivation on emotional working memory. Sixty‐one healthy participants (mean age: 23.4 years) were either sleep deprived for 1 night (n = 30) or had a normal night’s sleep (n = 31). They performed an N‐back task with two levels of working memory load (1‐back and 3‐back) using positive, neutral and negative picture scenes. Sleep deprivation, compared with full night sleep, impaired emotional working memory accuracy, but not reaction times. The sleep‐deprived participants, but not the controls, responded faster to positive than to negative and neutral pictures. The effect of sleep deprivation was similar for both high and low working memory loads. The results showed that although detrimental in terms of accuracy, sleep deprivation did not impair working memory speed. In fact, our findings indicate that positive stimuli may facilitate working memory processing speed after sleep deprivation.

  • 26. Gordon, Amy R.
    et al.
    Karshikoff, Bianka
    Kimball, Bruce A.
    Lundström, Johan N.
    Soop, Anne
    Sorjonen, Kimmo
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Axelsson, John
    Olsson, Mats J.
    The scent of disease2015In: Chemical Senses, ISSN 0379-864X, E-ISSN 1464-3553, Vol. 40, no 3, p. 254-254Article in journal (Refereed)
    Abstract [en]

    Ability to detect diseases in conspecifics would be advantageous for the individual. In line with this, rodents avoid body odors of infected individuals. Two studies (Olsson et al. 20014; in prep.) indicated that this is possible by way of human smell and human observers. T-shirts from donors (worn for 4 hours) that had received an injection of endotoxin [0.8ng lipopolysaccharide (LPS) / kg body weight], which causes systemic inflammation, smelled more unpleasant, intense, and sick than shirts from donors that had received a placebo (Saline) injection. GC/MS analysis of the shirts suggested that the change of body odor was not due to a general increase of odorous compounds in the “sick shirts” compared to “placebo shirts” but rather to a qualitative change. Study 2 (ongoing) further investigated the nature of this perception. In a first experiment, we compared the body odor of 30 endotoxin (0.6ng LPS / kg body weight) and 21 placebo (Saline) donors. Again, body odors were sampled during 4 hours using T-shirts. Observers then smelled the shirts and rated intensity, pleasantness, and disgust. In a second experiment, urine from these donors were collected and was investigated in the same way with subjective ratings. Altogether the data suggest that systemic inflammation makes body odors more aversive within a few hours.

  • 27. Gordon, Amy R.
    et al.
    Kimball, Bruce A.
    Sorionen, Kimmo
    Karshikoff, Bianka
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden; Stanford University, USA.
    Axelsson, John
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Lundström, Johan N.
    Olsson, Mats J.
    Detection of Inflammation via Volatile Cues in Human Urine2018In: Chemical Senses, ISSN 0379-864X, E-ISSN 1464-3553, Vol. 43, no 9, p. 711-719Article in journal (Refereed)
    Abstract [en]

    Contagious disease is a major threat to survival, and the cost of relying on the immune system to defeat pathogens is high; therefore, behavioral avoidance of contagious individuals is arguably an adaptive strategy. Animal findings demonstrate the ability to detect and avoid sick individuals by the aid of olfactory cues, and a recent study indicated that human axillary odor also becomes more aversive as a function of immune activation. By injecting healthy human participants with lipopolysaccharide (0.6 ng/kg body weight) to experimentally induce inflammation, this study demonstrates that natural daily rhythms of urine odor-its perceived dimensions and volatile profile-are altered within hours of inflammation onset. Whereas healthy human urine decreases in averseness over the course of a single day, inflammation interrupts this process and results in an increased urine odor averseness and an altered volatile composition. These results support the notion that subtle and early cues of sickness may be detected and avoided, thereby complementing the immune system in its role of keeping us alive and healthy.

  • 28. Guterstam, Joar
    et al.
    Hammarberg, Anders
    Wallhed Finn, Sara
    Cervenka, Simon
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Petrovic, Predrag
    Hedman, Erik
    "Dialogiskt golv" kan bli fallucka [Debatt]2015In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, no 112Article in journal (Other (popular science, discussion, etc.))
  • 29. Hedman, Erik
    et al.
    Andersson, Erik
    Andersson, Gerhard
    Lindefors, Nils
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Rück, Christian
    Ljótsson, Brjánn
    Mediators in internet-based cognitive behavior therapy for severe health anxiety2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 10, article id e77752Article in journal (Refereed)
    Abstract [en]

    According to the cognitive behavioral model of severe health anxiety (hypochondriasis) four central maintaining mechanisms are how the individual perceives the risk of disease and how negative its consequences would be, attention to bodily sensations, and intolerance of uncertainty. The aim of the present study was to investigate the mediating role of these putative mechanisms in Internet-delivered CBT for severe health anxiety. We analyzed data from an RCT where participants were randomized to Internet-delivered CBT (n=40) or to a control condition (n=41). Mediators and outcome, i.e. health anxiety, were assessed weekly throughout the treatment, enabling fulfillment of the criterion of temporal precedence of changes occurring in the mediator in relation to the outcome to be met. The results showed that reduced perceived risk of disease, less attention to bodily symptoms, and reduced intolerance of uncertainty significantly mediated improvement in health anxiety. The study supports the validity of the cognitive behavioral model of health anxiety. The findings have theoretical and clinical implications as they indicate processes that may be causally related to the improvements observed after CBT for health anxiety.

  • 30. Hedman, Erik
    et al.
    Andersson, Erik
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Ljótsson, Brjánn
    Predictors in Internet-delivered cognitive behavior therapy and behavioral stress management for severe health anxiety2015In: Behaviour Research and Therapy, ISSN 0005-7967, E-ISSN 1873-622X, Vol. 64, p. 49-55Article in journal (Refereed)
    Abstract [en]

    Severe health anxiety can be effectively treated with exposure-based Internet-delivered cognitive behavior therapy (ICBT), but information about which factors that predict outcome is scarce. Using data from a recently conducted RCT comparing ICBT (n = 79) with Internet-delivered behavioral stress management (IBSM) (n = 79) the presented study investigated predictors of treatment outcome. Analyses were conducted using a two-step linear regression approach and the dependent variable was operationalized both as end state health anxiety at post-treatment and as baseline-to post-treatment improvement. A hypothesis driven approach was used where predictors expected to influence outcome were based on a previous predictor study by our research group. As hypothesized, the results showed that baseline health anxiety and treatment adherence predicted both end state health anxiety and improvement. In addition, anxiety sensitivity, treatment credibility, and working alliance were significant predictors of health anxiety improvement. Demographic variables, i.e. age, gender, marital status, computer skills, educational level, and having children, had no significant predictive value. We conclude that it is possible to predict a substantial proportion of the outcome variance in ICBT and IBSM for severe health anxiety. The findings of the present study can be of high clinical value as they provide information about factors of importance for outcome in the treatment of severe health anxiety.

  • 31. Hedman, Erik
    et al.
    Andersson, Erik
    Ljótsson, Brjánn
    Axelsson, Erland
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden .
    Cost effectiveness of internet-based cognitive behaviour therapy and behavioural stress management for severe health anxiety2016In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 6, no 4, article id e009327Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Internet-delivered exposure-based cognitive behaviour therapy (ICBT) has been shown to be effective in the treatment of severe health anxiety. The health economic effects of the treatment have, however, been insufficiently studied and no prior study has investigated the effect of ICBT compared with an active psychological treatment. The aim of the present study was to investigate the cost effectiveness of ICBT compared with internet-delivered behavioural stress management (IBSM) for adults with severe health anxiety defined as Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) hypochondriasis. ICBT was hypothesised to be the more cost-effective treatment.

    SETTING: This was a cost-effectiveness study within the context of a randomised controlled trial conducted in a primary care/university setting. Participants from all of Sweden could apply to participate.

    PARTICIPANTS: Self-referred adults (N=158) with a principal diagnosis of DSM-IV hypochondriasis, of whom 151 (96%) provided baseline and post-treatment data.

    INTERVENTIONS: ICBT or IBSM for 12 weeks.

    PRIMARY AND SECONDARY MEASURES: The primary outcome was the Health Anxiety Inventory. The secondary outcome was the EQ-5D. Other secondary measures were used in the main outcome study but were not relevant for the present health economic analysis.

    RESULTS: Both treatments led to significant reductions in gross total costs, costs of healthcare visits, direct non-medical costs and costs of domestic work cutback (p=0.000-0.035). The incremental cost-effectiveness ratio (ICER) indicated that the cost of one additional case of clinically significant improvement in ICBT compared with IBSM was $2214. The cost-utility ICER, that is, the cost of one additional quality-adjusted life year, was estimated to be $10 000.

    CONCLUSIONS: ICBT is a cost-effective treatment compared with IBSM and treatment costs are offset by societal net cost reductions in a short time. A cost-benefit analysis speaks for ICBT to play an important role in increasing access to effective treatment for severe health anxiety.

    TRIAL REGISTRATION NUMBER: NCT01673035; Results.

  • 32. Hedman, Erik
    et al.
    Andersson, Gerhard
    Lindefors, Nils
    Gustavsson, Petter
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Rück, Christian
    Andersson, Erik
    Ljótsson, Brjánn
    Personality Change following Internet-Based Cognitive Behavior Therapy for Severe Health Anxiety2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 12, p. e113871-Article in journal (Refereed)
    Abstract [en]

    Personality traits have traditionally been viewed as stable, but recent studies suggest that they could be affected through psychological treatment. Internet-based cognitive behavior therapy (ICBT) for severe health anxiety (DSM-IV hypochondriasis) has been shown to be effective in reducing health anxiety, but its effect on measures of personality traits has not been investigated. The main aim of this study was to investigate the impact of ICBT on personality traits in the three broad dimensions -neuroticism, extraversion and aggression. We hypothesized that participants in ICBT would reduce their level of neuroticism compared to controls that did not receive the active treatment. No specific predictions were made regarding extraversion and aggression. Data from a randomized controlled trial were used in which participants were allocated to 12 weeks of ICBT (n=40) or to a basic attention control condition (n=41). Personality traits were assessed with the Swedish Universities Scales of Personality and the primary outcome of health anxiety was the Health Anxiety Inventory. There was a significant interaction effect of group and time on neuroticism-related scales, indicating larger pre-to post-treatment reductions in the Internet-based CBT group compared to the control condition. Analyses at 6-month follow-up showed that changes were stable. Traits relating to extraversion and aggression were largely unchanged. This study is the first to demonstrate that a brief ICBT intervention for severe health anxiety causes long-term changes in measures of personality traits related to neuroticism. The treatment thus has a broader impact than just reducing health anxiety.

  • 33. Hedman, Erik
    et al.
    Axelsson, Erland
    Andersson, Erik
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Ljótsson, Brjánn
    Exposure-based cognitive-behavioural therapy via the internet and as bibliotherapy for somatic symptom disorder and illness anxiety disorder: randomised controlled trial2016In: British Journal of Psychiatry, ISSN 0007-1250, E-ISSN 1472-1465, Vol. 209, no 5, p. 407-413Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: In DSM-5 two new diagnoses, somatic symptom disorder (SSD) and illness anxiety disorder (IAD), have replaced DSM-IV hypochondriasis. There are no previous treatment studies for these disorders. Cognitive-behavioural therapy (CBT) delivered as therapist-guided or unguided internet treatment or as unguided bibliotherapy could be used to increase treatment accessibility.

    AIMS: To investigate the effect of CBT delivered as guided internet treatment (ICBT), unguided internet treatment (U-ICBT) and as unguided bibliotherapy.

    METHOD: A randomised controlled trial (RCT) where participants (n = 132) with a diagnosis of SSD or IAD were randomised to ICBT, U-ICBT, bibliotherapy or to a control condition on a waiting list (trial registration: Clinicaltrials.gov identifier NCT01966705).

    RESULTS: Compared with the control condition, all three treatment groups made large and significant improvements on the primary outcome Health Anxiety Inventory (between-group d at post-treatment was 0.80-1.27).

    CONCLUSIONS: ICBT, U-ICBT and bibliotherapy can be highly effective in the treatment of SSD and IAD. This is the first study showing that these new DSM-5 disorders can be effectively treated.

  • 34. Hedman, Erik
    et al.
    Axelsson, Erland
    Görling, Anders
    Ritzman, Carina
    Ronnheden, Markus
    El Alaoui, Samir
    Andersson, Erik
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Ljótsson, Brjánn
    Internet-delivered exposure-based cognitive-behavioural therapy and behavioural stress management for severe health anxiety: randomised controlled trial2014In: British Journal of Psychiatry, ISSN 0007-1250, E-ISSN 1472-1465, Vol. 205, no 4, p. 307-314Article in journal (Refereed)
    Abstract [en]

    Background Exposure-based cognitive-behavioural therapy (CBT) delivered via the internet has been shown to be effective for severe health anxiety (hypochondriasis) but has not been compared with an active, effective and credible psychological treatment, such as behavioural stress management (BSM). Aims To investigate two internet-delivered treatments - exposure-based CBT v. BSM - for severe health anxiety in a randomised controlled trial (trial registration: NCT01673035). Method Participants (n = 158) with a principal diagnosis of severe health anxiety were allocated to 12 weeks of exposure-based CBT (n = 79) or BSM (n = 79) delivered via the internet. The Health Anxiety Inventory (HAI) was the primary outcome. Results Internet-delivered exposure-based CBT led to a significantly greater improvement on the HAI compared with BSM. However, both treatment groups made large improvements on the HAI (pre-to-post-treatment Cohen's d: exposure-based CBT, 1.78; BSM, 1.22). Conclusions Exposure-based CBT delivered via the internet is an efficacious treatment for severe health anxiety.

  • 35. Hedman, Erik
    et al.
    El Alaoui, Samir
    Lindefors, Nils
    Andersson, Erik
    Rück, Christian
    Ghaderi, Ata
    Kaldo, Viktor
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Andersson, Gerhard
    Ljótsson, Brjánn
    Clinical effectiveness and cost-effectiveness of Internet- vs. group-based cognitive behavior therapy for social anxiety disorder: 4-year follow-up of a randomized trial2014In: Behaviour Research and Therapy, ISSN 0005-7967, E-ISSN 1873-622X, Vol. 59, p. 20-29Article in journal (Refereed)
    Abstract [en]

    Social anxiety disorder (SAD) is common, debilitating and associated with high societal costs. The disorder can be effectively treated with Internet-based cognitive behavior therapy (ICBT), but no previous study has investigated the long-term clinical or health economic effects of ICBT for SAD in comparison to an evidence-based control treatment. The aim of the study was to investigate the clinical effectiveness and cost-effectiveness of ICBT compared to cognitive behavioral group therapy (CBGT) four years post-treatment. We conducted a 4-year follow-up study of participants who had received ICBT or CBGT for SAD within the context of a randomized controlled non-inferiority trial. The cost-effectiveness analyses were conducted taking a societal perspective. Participants in both treatment groups made large improvements from baseline to 4-year follow-up on the primary outcome measure (d = 1.34-1.48) and the 95% CI of the mean difference on the primary outcome was well within the non-inferiority margin. ICBT and CBGT were similarly cost-effective and both groups reduced their indirect costs. We conclude that ICBT for SAD yields large sustainable effects and is at least as long-term effective as CBGT. Intervention costs of both treatments are offset by net societal cost reductions in a short time.

  • 36. Hedman, Erik
    et al.
    Lekander, Mats
    Karshikoff, Bianka
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Ljótsson, Brjánn
    Axelsson, Erland
    Axelsson, John
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Health anxiety in a disease-avoidance framework: Investigation of anxiety, disgust and disease perception in response to sickness cues2016In: Journal of Abnormal Psychology, ISSN 0021-843X, E-ISSN 1939-1846, Vol. 125, no 7, p. 868-878Article in journal (Refereed)
    Abstract [en]

    Severe health anxiety is characterized by a debilitating fear of somatic illness, and avoidance of disease-related stimuli plays a key role in the maintenance of the disorder. The aim of this study was to investigate severe health anxiety within an evolutionary disease-avoidance framework. We hypothesized that, compared to healthy controls, participants with severe health anxiety would perceive others as sicker, more contagious, and less attractive. We also expected individuals with severe health anxiety to be more prone to avoid interaction with persons who appeared sick, as well as to respond with more health-related worry, more disgust, and more anxiety when confronting such individuals. In addition, this sensitivity was expected to be larger if people showed manifest sickness symptoms. Participants with and without severe health anxiety (N = 224) were exposed to facial photos with a varying degree of apparent sickness. Patients with severe health anxiety, compared to controls, rated apparently healthy people as being less healthy and less attractive. There were significant interaction effects showing that that the increase in disgust, anxiety, perceived contagiousness, and worry over one's own health as a function of how sick the person in the photo appeared, was significantly larger in the clinical sample compared to the healthy control sample (ps < .047). Results from regression analyses using health anxiety as a dimensional predictor also supported our hypotheses. We suggest that disgust and cognitive biases relating to the disease-avoidance model are significant features of severe health anxiety. (PsycINFO Database Record

  • 37. Hedman, Erik
    et al.
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Ljótsson, Brjánn
    Lindefors, Nils
    Rück, Christian
    Andersson, Gerhard
    Andersson, Erik
    Optimal cut-off points on the health anxiety inventory, illness attitude scales and whiteley index to identify severe health anxiety2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 4, article id e0123412Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Health anxiety can be viewed as a dimensional phenomenon where severe health anxiety in form of DSM-IV hypochondriasis represents a cut-off where the health anxiety becomes clinically significant. Three of the most reliable and used self-report measures of health anxiety are the Health Anxiety Inventory (HAI), the Illness Attitude Scales (IAS) and the Whiteley Index (WI). Identifying the optimal cut-offs for classification of presence of a diagnosis of severe health anxiety on these measures has several advantages in clinical and research settings. The aim of this study was therefore to investigate the HAI, IAS and WI as proximal diagnostic instruments for severe health anxiety defined as DSM-IV hypochondriasis.

    METHODS: We investigated sensitivity, specificity and predictive value on the HAI, IAS and WI using a total of 347 adult participants of whom 158 had a diagnosis of severe health anxiety, 97 had obsessive-compulsive disorder and 92 were healthy non-clinical controls. Diagnostic assessments were conducted using the Anxiety Disorder Interview Schedule.

    RESULTS: Optimal cut-offs for identifying a diagnosis of severe health anxiety was 67 on the HAI, 47 on the IAS, and 5 on the WI. Sensitivity and specificity were high, ranging from 92.6 to 99.4%. Positive and negative predictive values ranged from 91.6 to 99.4% using unadjusted prevalence rates.

    CONCLUSIONS: The HAI, IAS and WI have very good properties as diagnostic indicators of severe health anxiety and can be used as cost-efficient proximal estimates of the diagnosis.

  • 38. Hedman, Erik
    et al.
    Lekander, Mats
    Karolinska Institutet, Sweden.
    Ljótsson, Brjánn
    Lindefors, Nils
    Rück, Christian
    Hofmann, Stefan G
    Andersson, Erik
    Andersson, Gerhard
    Schulz, Stefan M
    Sudden gains in internet-based cognitive behaviour therapy for severe health anxiety2014In: Behaviour Research and Therapy, ISSN 0005-7967, E-ISSN 1873-622X, Vol. 54, p. 22-29Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: A sudden gain is defined as a large and stable individual improvement occurring between two consecutive treatment sessions. Sudden gains have been shown to predict better long-term improvement in several treatment studies, including cognitive behavioural therapy for depression and anxiety disorders, but have not been studied in the treatment of health anxiety or any form of internet-based cognitive behavioural therapy. The aim of this study was to investigate the role of sudden gains in internet-based cognitive behavioural therapy for severe health anxiety.

    METHOD: We examined the occurrence and significance of sudden gains in measures of health anxiety in 81 participants receiving internet-based cognitive behavioural therapy. We compared patients with sudden gains, patients without sudden gains, and patients with gradual gains.

    RESULTS: Thirteen participants (16%) experienced one sudden gain in health anxiety with individual sudden gains distributed across the treatment. As expected, patients with a sudden gain showed larger improvements than patients without a sudden gain at post-treatment (d = 1.04) and at one-year follow-up (d = 0.91) on measures of health anxiety.

    CONCLUSIONS: Consistent with previous studies, sudden gains in internet-based cognitive behavioural therapy are associated with significantly larger and stable treatment effects up to one-year follow-up.

  • 39. Hedman, Erik
    et al.
    Lindefors, Nils
    Andersson, Gerhard
    Andersson, Erik
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Rück, Christian
    Ljótsson, Brjánn
    Predictors of outcome in Internet-based cognitive behavior therapy for severe health anxiety2013In: Behaviour Research and Therapy, ISSN 0005-7967, E-ISSN 1873-622X, Vol. 51, no 10, p. 711-717Article in journal (Refereed)
    Abstract [en]

    Internet-based cognitive behavior therapy (CBT) for severe health anxiety can be effective, but not all patients achieve full remission. Under these circumstances, knowledge about predictors is essential for the clinician in order to make reliable treatment recommendations. The primary aim of this study was to investigate clinical, demographic, and therapy process-related predictors of Internet-based CBT for severe health anxiety. We performed three types of analyses on data from a sample comprising participants (N = 81) who had received Internet-based CBT in a randomized controlled trial. Outcomes were a) end state health anxiety, b) improvement in health anxiety (continuous change scores), and c) clinically significant improvement. Outcomes were assessed at six-month follow-up. The results showed that the most stable predictors of both end state health anxiety and improvement were baseline health anxiety and depressive symptoms. Treatment adherence, i.e. the number of completed treatment modules, also significantly predicted outcome. Notably, health anxiety at baseline was positively associated with symptom improvement while depressive symptoms was negatively related to improvement. Demographic factors were largely without significant impact on end state symptoms or improvement. We conclude that baseline symptom burden and adherence to treatment have strong predictive effects in Internet-based CBT for severe health anxiety.

  • 40. Hedman, Erik
    et al.
    Ljótsson, Brjánn
    Andersson, Erik
    Andersson, Gerhard
    Lindefors, Nils
    Rück, Christian
    Axelsson, Erland
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Psychometric properties of Internet-administered measures of health anxiety: an investigation of the Health Anxiety Inventory, the Illness Attitude Scales, and the Whiteley Index2015In: Journal of Anxiety Disorders, ISSN 0887-6185, E-ISSN 1873-7897, Vol. 31, p. 32-37Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The Health Anxiety Inventory (HAI), the Illness Attitude Scales (IAS), and the Whiteley Index (WI) are three of the most widely used health anxiety measures, but their psychometric properties have not been investigated when administered via the Internet.

    METHODS: We investigated the three instruments' test-retest reliability, internal consistency, convergent, and discriminant validity and sensitivity to change using one sample (n=111) of participants with severe health anxiety and one sample of healthy controls (n=92).

    RESULTS: The HAI, IAS, and WI showed high test-retest reliability (rs≥.80), good convergent, and discriminant validity and were sensitive to detect change. The HAI and IAS (αs≥.85), but not the WI (αs≤.60) demonstrated high internal consistency.

    CONCLUSIONS: The HAI, IAS, and WI have good psychometric properties, except for the low internal consistency of WI, when used as Internet-administered measures of health anxiety. Using these measures over the Internet offers highly important advantages such as increased ease of administration, reduced attrition, and cost-efficient treatment evaluation.

  • 41. Hedman, Erik
    et al.
    Mörtberg, Ewa
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Hesser, Hugo
    Clark, David M.
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Andersson, Erik
    Ljótsson, Brjánn
    Mediators in psychological treatment of social anxiety disorder: Individual cognitive therapy compared to cognitive behavioral group therapy2013In: Behaviour Research and Therapy, ISSN 0005-7967, E-ISSN 1873-622X, Vol. 51, no 10, p. 696-705Article in journal (Refereed)
    Abstract [en]

    According to cognitive-behavioral models of social anxiety disorder (SAD), four of the important maintaining mechanisms are avoidance, self-focused attention, anticipatory processing and post-event cognitive processing. Individual cognitive therapy (ICT) and cognitive behavioral group therapy (CBGT) both have substantial empirical support. However, it is unclear whether they achieve their effects by similar or different mechanisms. The aim of this study was to investigate whether changes in the four maintenance processes mediate clinical improvement in ICT and CBGT for SAD. We analyzed data from participants (N = 94) who received either ICT or CBGT in two separate RCTs. The results showed that ICT had larger effects than CBGT on social anxiety and each of the four potential mediators. More pertinently, moderated mediation analyses revealed significant between-treatment differences. Whereas improvement in ICT was mainly mediated by reductions in avoidance and self-focused attention, improvement in CBGT was mediated by changes in self-focused attention and in anticipatory and post-event processing. These results support the importance of the putative mediators, but suggest that their relative weights are moderated by treatment type.

  • 42. Hedman-Lagerlöf, Erik
    et al.
    Axelsson, Erland
    Andersson, Erik
    Ljotsson, Brjann
    Andreasson, Anna
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden; Macquarie University, Australia.
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    The impact of exposure-based cognitive behavior therapy for severe health anxiety on self-rated health: Results from a randomized trial2017In: Journal of Psychosomatic Research, ISSN 0022-3999, E-ISSN 1879-1360, Vol. 103, p. 9-14Article in journal (Refereed)
    Abstract [en]

    Objective: Self-rated health (SRH) has been shown to be a stable predictor of illness and mortality. Improvement in SRH, even in the absence of change in objective health, predicts better health and reduced mortality. Severe health anxiety (SHA) is characterized by fear of illness and distorted health perception. The objective of the present study was to investigate if exposure-based cognitive behavior therapy (CBT) for SHA can lead to improvement in SRH and whether this improvement is mediated by reduced health anxiety. Methods: Data were collected from a randomized controlled trial where participants with SHA were allocated to 12 weeks of exposure-based CBT (n = 99) for SHA or to a no treatment control condition (n = 33). The mediation analysis was based on SRH- and health anxiety data collected weekly during the treatment phase. Results: Linear mixed effects models analysis showed a significant interaction effect of group and time indicating superior improvements in SRH in exposure-based CBT compared to the control condition (Z = 2.69, p = 0.007). The controlled effect size was moderately large (d = 0.64) and improvements were stable at 1-year follow-up. Reduced health anxiety was a significant mediator of improvement in SRH. Conclusions: 12 weeks of exposure-based CBT for SHA can lead to significant improvements in SRH. Considering the previously established importance of SRH as a predictor for disease and mortality, exposure-based CBT for severe health anxiety may lead to improvements on several important health parameters, possibly even increasing the likelihood of longevity.

  • 43. Henderson, Audrey J.
    et al.
    Lasselin, Julie
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden; Institute of Medical Psychology and Behavioral Immunobiology, Germany.
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Olsson, Mats J.
    Powis, Simon J.
    Axelsson, John
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Perrett, David I.
    Skin colour changes during experimentally-induced sickness2017In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 60, p. 312-318Article in journal (Refereed)
    Abstract [en]

    Skin colour may be an important cue to detect sickness in humans but how skin colour changes with acute sickness is currently unknown. To determine possible colour changes, 22 healthy Caucasian participants were injected twice, once with lipopolysaccharide (LPS, at a dose of 2ng/kg body weight) and once with placebo (saline), in a randomised cross-over design study. Skin colour across 3 arm and 3 face locations was recorded spectrophotometrically over a period of 8h in terms of lightness (L(∗)), redness (a(∗)) and yellowness (b(∗)) in a manner that is consistent with human colour perception. In addition, carotenoid status was assessed as we predicted that a decrease it skin yellowness would reflect a drop in skin carotenoids. We found an early change in skin colouration 1-3h post LPS injection with facial skin becoming lighter and less red whilst arm skin become darker but also less red and less yellow. The LPS injection also caused a drop in plasma carotenoids from 3h onwards. However, the timing of the carotenoid changes was not consistent with the skin colour changes suggesting that other mechanisms, such as a reduction of blood perfusion, oxygenation or composition. This is the first experimental study characterising skin colour associated with acute illness, and shows that changes occur early in the development of the sickness response. Colour changes may serve as a cue to health, prompting actions from others in terms of care-giving or disease avoidance. Specific mechanisms underlying these colour changes require further investigation.

  • 44. Henje Blom, Eva
    et al.
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Ingvar, Martin
    Åsberg, Marie
    Mobarrez, Fariborz
    Serlachius, Eva
    Pro-inflammatory cytokines are elevated in adolescent females with emotional disorders not treated with SSRIs2012In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 136, no 3, p. 716-23Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Adults with major depressive disorder (MDD) show elevated levels of IL-6 and TNF-alpha. Studies of adolescents with MDD or anxiety disorders (AD) are few and present conflicting results.

    METHODS: We studied plasma cytokines in a clinical sample of adolescent females with MDD and/or clinical AD (n=60, mean age 16.8 years), compared to healthy controls (n=44; mean age 16.5 years).

    RESULTS: The clinical sample showed significantly higher values of IL-2 (Z=-4.09, p>0.0001), IL1-beta (Z=-2.40, p<0.05) and IL-10 (Z=-2.38, p<0.05) as compared to controls. The subgroup of the clinical sample not treated with SSRIs had a significant difference of IL-6 (Z=-2.26, p<0.05) in addition to the difference of IL-2 and IL1-beta, but showed no difference of IL-10 as compared to the controls. SSRI treatment was related to IL-6, explaining 26% of the variance in the clinical sample after controlling for BMI and symptom severity. In the clinical sample, levels of IL-6 and IFN-gamma were positively correlated with self-assessed symptoms of anxiety and/or depression (corr.coeff 0.35 resp 0.40 at p<0.05).

    LIMITATIONS: The cross-sectional design does not allow for conclusions on causality. The sample sizes were relatively small and a large drop-out in the clinical sample may have influenced the representativity.

    DISCUSSION: The study suggests that pro-inflammatory cytokines are part of the pathophysiology of emotional disorders in adolescent females and that SSRIs have anti-inflammatory properties. The findings prompt further studies on the specific mechanisms involved and may contribute to the development of more effective treatment and prevention.

  • 45. Hjelmstedt, Anna
    et al.
    Shenoy, Sheela T.
    Stener-Victorin, Elisabeth
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Department of Political Science.
    Bhat, Mamta
    Balakumaran, Leena
    Waldenström, Ulla
    Acupressure to reduce labor pain: a randomized controlled trial2010In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 89, no 11, p. 1453-1459Article in journal (Refereed)
    Abstract [en]

    Abstract Objective. To evaluate the effect of acupressure administered during the active phase of labor on nulliparous women's ratings of labor pain. Design. Randomized controlled trial. Setting. Public hospital in India. Sample. Seventy-one women randomized to receive acupressure at acupuncture point spleen 6 (SP6) on both legs during contractions over a 30-minute period (acupressure group), 71 women to receive light touch at SP6 on both legs during the same period of time (touch group) and 70 women to receive standard care (standard care group). Methods. Experience of in-labor pain was assessed by visual analog scale at baseline before treatment, immediately after treatment, and at 30, 60 and 120 minutes after treatment. Main outcome measure. Labor pain intensity at different time intervals after treatment compared with before treatment. Results. A reduction of in-labor pain was found in the acupressure group and was most noticeable immediately after treatment (acupressure group vs. standard care group p < 0.001; acupressure group vs. touch group p < 0.001). Conclusion. Acupressure seems to reduce pain during the active phase of labor in nulliparous women giving birth in a context in which social support and epidural analgesia are not available. However, the treatment effect is small which suggests that acupressure may be most effective during the initial phase of labor.

  • 46. Holding, Benjamin C.
    et al.
    Sundelin, Tina
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Axelsson, John
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Sleep deprivation and its effects on communication during individual and collaborative tasks2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 3131Article in journal (Refereed)
    Abstract [en]

    Sleep loss has been shown to cause impairments in a number of aspects central for successful communication, ranging from poorer linguistic comprehension to alterations in speech prosody. However, the effect of sleep loss on actual communication is unknown. This study investigated how a night of sleep deprivation affected performance during multiple tasks designed to test verbal communication. Healthy participants (N = 183) spent 8-9 hours per night in bed for three nights and were then randomised to either one night of total sleep deprivation or a fourth night with 8-9 hours in bed. The following day, participants completed two tasks together with another participant: a model-building task and a word-description task. Differences in performance of these tasks were assessed alongside speaking duration, speaking volume, and speaking volume consistency. Additionally, participants individually completed a verbal fluency assessment. Performance on the model-building task was worse if the model-builder was sleep deprived, whereas sleep deprivation in the instruction-giver predicted an improvement. Word-description, verbal fluency, speech duration, speaking volume, and speaking volume consistency were not affected. The results suggest that sleep deprivation leads to changes in communicative performance during instructive tasks, while simpler word-description tasks appear resilient.

  • 47. Jernelov, S.
    et al.
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Almqvist, C.
    Axelsson, John
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Larsson, H.
    Development of atopic disease and disturbed sleep in childhood and adolescence a longitudinal population-based study2013In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 43, no 5, p. 552-559Article in journal (Refereed)
    Abstract [en]

    Background Both atopic diseases and sleep disturbances have increased during recent decades, especially in children. Sleep is important for many aspects of immune regulation relevant in allergic diseases, and sleep disturbances are common in patients with such diseases. A connection between sleep disturbances and fatigue, and atopic disease is well established. However, the time course and putative causal relationships between these factors are obscure.

    Objective We aimed at investigating the developmental relationships between subjectively reported sleep disturbances and symptoms of atopic disease, from childhood to adolescence.

    Methods This longitudinal study used parent-report questionnaire data on symptoms of atopic disease, and sleep disturbances, from the Twin Study of Child and Adolescent Development (TCHAD). Overall, 1480 twin pairs born in Sweden were approached first when children were 89years old, and again later at 1314years old. Response rates were 75% and 72%. Data from the TCHAD questionnaires were linked to the Swedish Medical Birth Register based on personal identification numbers.

    Results Being overtired at age 8 increased the risk [OR; 95% CI (2.59; 1.315.11)] to develop rhinitis symptoms at age 13, even when controlling for gender, previous rhinitis, Socio-economic status, birth weight and other sleep disturbances at age 8. Likewise, symptoms of asthma at age 8 was an independent risk factor for being overtired at age 13 [OR; 95% CI (2.64; 1.444.84)], controlling for similar confounders.

    Conclusion & Clinical Relevance The findings from this study are consonant with the proposition that atopic disease and disturbed sleep are more than passively interrelated. Future research needs to delineate whether causal relationships between these problems are at hand and, if so, at what periods in development this applies. These results point to a need for clinicians to investigate sleep difficulties and treat impaired sleep in paediatric patients with atopic disease.

  • 48. Jernelöv, Susanna
    et al.
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Blom, Kerstin
    Rydh, Sara
    Ljótsson, Brjánn
    Axelsson, John
    Kaldo, Viktor
    Efficacy of a behavioral self-help treatment with or without therapist guidance for co-morbid and primary insomnia - a randomized controlled trial2012In: BMC Psychiatry, ISSN 1471-244X, E-ISSN 1471-244X, no 12, article id 5Article in journal (Refereed)
    Abstract [en]

    Background

    Cognitive behavioral therapy is treatment of choice for insomnia, but availability is scarce. Self-help can increase availability at low cost, but evidence for its efficacy is limited, especially for the typical insomnia patient with co-morbid problems. We hypothesized that a cognitive behaviorally based self-help book is effective to treat insomnia in individuals, also with co-morbid problems, and that the effect is enhanced by adding brief therapist telephone support.

    Methods

    Volunteer sample; 133 media-recruited adults with insomnia. History of sleep difficulties (mean [SD]) 11.8 [12.0] years. 92.5% had co-morbid problems (e.g. allergy, pain, and depression). Parallel randomized (block-randomization, n ≥ 21) controlled "open label" trial; three groups-bibliotherapy with (n = 44) and without (n = 45) therapist support, and waiting list control (n = 44). Assessments before and after treatment, and at three-month follow-up. Intervention was six weeks of bibliotherapeutic self-help, with established cognitive behavioral methods including sleep restriction, stimulus control, and cognitive restructuring. Therapist support was a 15-minute structured telephone call scheduled weekly. Main outcome measures were sleep diary data, and the Insomnia Severity Index.

    Results

    Intention-to-treat analyses of 133 participants showed significant improvements in both self-help groups from pre to post treatment compared to waiting list. For example, treatment with and without support gave shorter sleep onset latency (improvement minutes [95% Confidence Interval], 35.4 [24.2 to 46.6], and 20.6 [10.6 to 30.6] respectively), and support gave a higher remission rate (defined as ISI score below 8; 61.4%), than bibliotherapy alone (24.4%, p's < .001). Improvements were not seen in the control group (sleep onset latency 4.6 minutes shorter [-1.5 to 10.7], and remission rate 2.3%). Self-help groups maintained gains at three-month follow-up.

    Conclusions

    Participants receiving self-help for insomnia benefited markedly. Self-help, especially if therapist-supported, has considerable potential to be as effective as individual treatment at lower cost, also for individuals with co-morbid problems.

  • 49. Kanegawa, Naoki
    et al.
    Collste, Karin
    Forsberg, Anton
    Schain, Martin
    Arakawa, Ryosuke
    Jucaite, Aurelija
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Olgart Höglund, Caroline
    Kosek, Eva
    Lampa, Jon
    Halldin, Christer
    Farde, Lars
    Varrone, Andrea
    Cervenka, Simon
    In vivo evidence of a functional association between immune cells in blood and brain in healthy human subjects2016In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 54, p. 149-157Article in journal (Refereed)
    Abstract [en]

    Microglia, the resident macrophages in the central nervous system, are thought to be maintained by a local self-renewal mechanism. Although preclinical and in vitro studies have suggested that the brain may contain immune cells also from peripheral origin, the functional association between immune cells in the periphery and brain at physiological conditions is poorly understood. We examined 32 healthy individuals using positron emission tomography (PET) and [(11)C]PBR28, a radioligand for the 18-kDa translocator protein (TSPO) which is expressed both in brain microglia and blood immune cells. In 26 individuals, two measurements were performed with varying time intervals. In a subgroup of 19 individuals, of which 12 had repeat examinations, leukocyte numbers in blood was measured on each day of PET measurements. All individuals were genotyped for TSPO polymorphism and categorized as high, mixed, and low affinity binders. We assessed TSPO binding expressed as total distribution volume of [(11)C]PBR28 in brain and in blood cells. TSPO binding in brain was strongly and positively correlated to binding in blood cells both at baseline and when analyzing change between two PET examinations. Furthermore, there was a significant correlation between change of leukocyte numbers and change in TSPO binding in brain, and a trend-level correlation to change in TSPO binding in blood cells. These in vivo findings indicate an association between immunological cells in blood and brain via intact BBB, suggesting a functional interaction between these two compartments, such as interchange of peripherally derived cells or a common regulatory mechanism. Measurement of radioligand binding in blood cells may be a way to control for peripheral immune function in PET studies using TSPO as a marker of brain immune activation.

  • 50. Kanstrup, Marie
    et al.
    Wicksell, Rikard K.
    Kemani, Mike
    Lipsker, Camilla Wiwe
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Holmström, Linda
    A Clinical Pilot Study of Individual and Group Treatment for Adolescents with Chronic Pain and Their Parents: Effects of Acceptance and Commitment Therapy on Functioning2016In: Children, ISSN 2227-9067, Vol. 3, no 4, article id 30Article in journal (Refereed)
    Abstract [en]

    Pediatric chronic pain is common and can result in substantial long-term disability. Previous studies on acceptance and commitment therapy (ACT) have shown promising results in improving functioning in affected children, but more research is still urgently needed. In the current clinical pilot study, we evaluated an ACT-based interdisciplinary outpatient intervention (14 sessions), including a parent support program (four sessions). Adolescents were referred to the clinic if they experienced disabling chronic pain. They were then randomized, along with their parents, to receive group (n = 12) or individual (n = 18) treatment. Adolescent pain interference, pain reactivity, depression, functional disability, pain intensity and psychological flexibility, along with parent anxiety, depression, pain reactivity and psychological flexibility were assessed using self-reported questionnaires. There were no significant differences in outcomes between individual and group treatment. Analyses illustrated significant (p < 0.01) improvements (medium to large effects) in pain interference, depression, pain reactivity and psychological flexibility post-treatment. Additionally, analyses showed significant (p < 0.01) improvements (large effects) in parent pain reactivity and psychological flexibility post-treatment. On all significant outcomes, clinically-significant changes were observed for 21%-63% of the adolescents across the different outcome measures and in 54%-76% of the parents. These results support previous findings and thus warrant the need for larger, randomized clinical trials evaluating the relative utility of individual and group treatment and the effects of parental interventions.

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