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  • 1.
    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.

  • 2.
    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.

  • 3.
    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.

  • 4.
    Axelsson, John
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Sleep, appearance and social interactions2014Conference paper (Other academic)
  • 5.
    Axelsson, John
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Kecklund, Göran
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Sömn och fysisk aktivitet2016In: FYSS 2017: fysisk aktivitet i sjukdomsprevention och sjukdomsbehandling, Stockholm: Läkartidningen förlag AB , 2016, 3, p. 171-183Chapter in book (Other academic)
  • 6.
    Axelsson, John
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Kecklund, Göran
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Tigerström, L
    Does rapid eye movement (REM) sleep prepare the brain for wakening?2014In: Journal of sleep research, Special issue: 22nd Congress of the European Sleep Research Society, 16-20 September, 2014, Tallinn, Estonia, 2014Conference paper (Other academic)
  • 7.
    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)
  • 8.
    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)
  • 9.
    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.

  • 10.
    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)
  • 11.
    Axelsson, John
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Sundelin, Tina
    Olsson, Mats J.
    Sorjonen, Kimmo
    Axelsson, Charlotte
    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.
    Identification of acutely sick people and facial cues of sickness2018In: Proceedings of the Royal Society of London. Biological Sciences, ISSN 0962-8452, E-ISSN 1471-2954, Vol. 285, no 1870, article id 20172430Article in journal (Refereed)
    Abstract [en]

    Detection and avoidance of sick individuals have been proposed as essential components in a behavioural defence against disease, limiting the risk of contamination. However, almost no knowledge exists on whether humans can detect sick individuals, and if so by what cues. Here, we demonstrate that untrained people can identify sick individuals above chance level by looking at facial photos taken 2 h after injection with a bacterial stimulus inducing an immune response (2.0 ng kg-1 lipopolysaccharide) or placebo, the global sensitivity index being d' = 0.405. Signal detection analysis (receiver operating characteristic curve area) showed an area of 0.62 (95% confidence intervals 0.60-0.63). Acutely sick people were rated by naive observers as having paler lips and skin, a more swollen face, droopier corners of the mouth, more hanging eyelids, redder eyes, and less glossy and patchy skin, as well as appearing more tired. Our findings suggest that facial cues associated with the skin, mouth and eyes can aid in the detection of acutely sick and potentially contagious people.

  • 12.
    Axelsson, John
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institute, Sweden.
    Vyazovskiy, Vladyslav V.
    Banking Sleep and Biological Sleep Need2015In: Sleep, ISSN 0161-8105, E-ISSN 1550-9109, Vol. 38, no 12, p. 1843-1845Article in journal (Refereed)
  • 13.
    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.

  • 14.
    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.

  • 15.
    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.

  • 16.
    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.

  • 17. 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.

  • 18. 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

  • 19. 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.

  • 20. Holding, Benjamin C.
    et al.
    Laukka, Petri
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Cognitive psychology.
    Fischer, Håkan
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Biological psychology.
    Bänziger, Tanja
    Axelsson, John
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Sundelin, Tina
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Multimodal Emotion Recognition Is Resilient to Insufficient Sleep: Results From Cross-Sectional and Experimental Studies2017In: Sleep, ISSN 0161-8105, E-ISSN 1550-9109, Vol. 40, no 11, article id zsx145Article in journal (Refereed)
    Abstract [en]

    Objectives: Insufficient sleep has been associated with impaired recognition of facial emotions. However, previous studies have found inconsistent results, potentially stemming from the type of static picture task used. We therefore examined whether insufficient sleep was associated with decreased emotion recognition ability in two separate studies using a dynamic multimodal task.

    Methods: Study 1 used a cross-sectional design consisting of 291 participants with questionnaire measures assessing sleep duration and self-reported sleep quality for the previous night. Study 2 used an experimental design involving 181 participants where individuals were quasi-randomized into either a sleep-deprivation (N = 90) or a sleep-control (N = 91) condition. All participants from both studies were tested on the same forced-choice multimodal test of emotion recognition to assess the accuracy of emotion categorization.

    Results: Sleep duration, self-reported sleep quality (study 1), and sleep deprivation (study 2) did not predict overall emotion recognition accuracy or speed. Similarly, the responses to each of the twelve emotions tested showed no evidence of impaired recognition ability, apart from one positive association suggesting that greater self-reported sleep quality could predict more accurate recognition of disgust (study 1).

    Conclusions: The studies presented here involve considerably larger samples than previous studies and the results support the null hypotheses. Therefore, we suggest that the ability to accurately categorize the emotions of others is not associated with short-term sleep duration or sleep quality and is resilient to acute periods of insufficient sleep.

  • 21. Holding, Benjamin C.
    et al.
    Sundelin, Tina
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden; New York University, NY, USA.
    Cairns, Patrick
    Perrett, David I.
    Axelsson, John
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    The effect of sleep deprivation on objective and subjective measures of facial appearance2019In: Journal of Sleep Research, ISSN 0962-1105, E-ISSN 1365-2869, Vol. 28, no 6, article id e12860Article in journal (Refereed)
    Abstract [en]

    The faces of people who are sleep deprived are perceived by others as looking paler, less healthy and less attractive compared to when well rested. However, there is little research using objective measures to investigate sleep-loss-related changes in facial appearance. We aimed to assess the effects of sleep deprivation on skin colour, eye openness, mouth curvature and periorbital darkness using objective measures, as well as to replicate previous findings for subjective ratings. We also investigated the extent to which these facial features predicted ratings of fatigue by others and could be used to classify the sleep condition of the person. Subjects (n = 181) were randomised to one night of total sleep deprivation or a night of normal sleep (8-9 hr in bed). The following day facial photographs were taken and, in a subset (n = 141), skin colour was measured using spectrophotometry. A separate set of participants (n = 63) later rated the photographs in terms of health, paleness and fatigue. The photographs were also digitally analysed with respect to eye openness, mouth curvature and periorbital darkness. The results showed that neither sleep deprivation nor the subjects' sleepiness was related to differences in any facial variable. Similarly, there was no difference in subjective ratings between the groups. Decreased skin yellowness, less eye openness, downward mouth curvature and periorbital darkness all predicted increased fatigue ratings by others. However, the combination of appearance variables could not be accurately used to classify sleep condition. These findings have implications for both face-to-face and computerised visual assessment of sleep loss and fatigue.

  • 22. 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.

  • 23. 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.

  • 24. Karshikoff, B.
    et al.
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Soop, A.
    Lindstedt, F.
    Ingvar, M.
    Kosek, E.
    Olgart Höglund, C.
    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.
    Modality and sex differences in pain sensitivity during human endotoxemia2014In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 46, p. 35-43Article in journal (Refereed)
    Abstract [en]

    Systemic inflammation can induce pain hypersensitivity in animal and human experimental models, and has been proposed to be central in clinical pain conditions. Women are overrepresented in many chronic pain conditions, but experimental studies on sex differences in pain regulation during systemic inflammation are still scarce. In two randomized and double blind placebo controlled experiments, we used low doses of lipopolysaccharide (LPS) as an experimental model of systemic inflammation. The first study employed 0.8ng/kg LPS in a within-subject design of 8 individuals (1 woman), and the second study 0.6ng/kg LPS in a between-subject design of 52 participants (29 women). We investigated the effect on (a) pressure, heat, and cold pain thresholds, (b) suprathreshold noxious heat and cold sensitivity, and (c) conditioned pain modulation (CPM), and differences between men and women. LPS induced significantly lower pressure pain thresholds as compared to placebo (mean change with the 0.8ng/kg dose being -64±30kPa P=.04; with the 0.6ng/kg dose -58±55kPa, P<.01, compared to before injection), whereas heat and cold pain thresholds remained unaffected (P's>.70). Suprathreshold noxious pain was not affected by LPS in men (P's⩾.15). However, LPS made women rated suprathreshold noxious heat stimuli as more painful (P=.01), and showed a tendency to rate noxious cold pain as more painful (P=.06) as compared to placebo. Furthermore, LPS impaired conditioned pain modulation, a measure of endogenous pain inhibition, but this effect was also restricted to women (P<.01, for men P=.27). Pain sensitivity correlated positively with plasma IL-6 and IL-8 levels. The results show that inflammation more strongly affects deep pain, rather than cutaneous pain, and suggest that women's pain perception and modulation is more sensitive to immune activation than men's.

  • 25.
    Karshikoff, Bianka
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska University Hospital, Sweden; Karolinska Institutet, Sweden.
    Jensen, K. B.
    Kosek, E.
    Kalpouzos, Grégoria
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Soop, A.
    Ingvar, M.
    Olgart Höglund, C.
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska University Hospital, Sweden; Karolinska Institutet, Sweden.
    Axelsson, John
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska University Hospital, Sweden; Karolinska Institutet, Sweden.
    Why sickness hurts: A central mechanism for pain induced by peripheral inflammation2016In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 57, p. 38-46Article in journal (Refereed)
    Abstract [en]

    Low-grade systemic inflammation has been implicated in chronic pain, as well as in comorbid diseases like depression and fatigue. We have previously shown that women's pain perception and regulation is more affected by systemic inflammation than that of men. Here we investigated the neural substrates underlying these effects using an fMRI paradigm previously employed in a clinical population. Fifty-one participants (29 women) were injected with 0.6ng/kg lipopolysaccharide (LPS) or saline to induce a peripheral inflammatory response. The subjects were then tested with a pressure pain fMRI paradigm designed to capture descending pain inhibitory activity 2h after injection, and blood was sampled for cytokine analysis. The subjects injected with LPS became more pain sensitive compared to the placebo group, and the heightened pain sensitivity was paralleled by decreased activity in the ventrolateral prefrontal cortex and the rostral anterior cingulate cortex (rACC) compared to placebo; areas involved in descending pain regulation. The LPS group also had higher activity in the anterior insular cortex, an area underpinning affective and interoceptive pain processing. Women displayed overall less pain-evoked rACC activity compared to men, which may have rendered women less resilient to immune provocation, possibly explaining sex differences in LPS-induced pain sensitivity. Our findings elucidate the pain-related brain circuits affected by experimental peripheral inflammation, strengthening the theoretical link between systemic inflammation and weakened pain regulation in chronic pain disorders. The results further suggest a possible mechanism underlying the female predominance in many chronic pain disorders.

  • 26.
    Kecklund, Göran
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Radboud University, Netherlands.
    Axelsson, John
    Health consequences of shift work and insufficient sleep2016In: BMJ. British Medical Journal, E-ISSN 1756-1833, Vol. 355, article id i5210Article, review/survey (Refereed)
    Abstract [en]

    This review summarises the literature on shift work and its relation to insufficient sleep, chronic diseases, and accidents. It is based on 38 meta-analyses and 24 systematic reviews, with additional narrative reviews and articles used for outlining possible mechanisms by which shift work may cause accidents and adverse health. Evidence shows that the effect of shift work on sleep mainly concerns acute sleep loss in connection with night shifts and early morning shifts. A link also exists between shift work and accidents, type 2 diabetes (relative risk range 1.09-1.40), weight gain, coronary heart disease (relative risk 1.23), stroke (relative risk 1.05), and cancer (relative risk range 1.01-1.32), although the original studies showed mixed results. The relations of shift work to cardiometabolic diseases and accidents mimic those with insufficient sleep. Laboratory studies indicate that cardiometabolic stress and cognitive impairments are increased by shift work, as well as by sleep loss. Given that the health and safety consequences of shift work and insufficient sleep are very similar, they are likely to share common mechanisms. However, additional research is needed to determine whether insufficient sleep is a causal pathway for the adverse health effects associated with shift work.

  • 27.
    Kecklund, Göran
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Sallinen, Mikael
    Axelsson, John
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Optimizing Shift Scheduling2016In: Principles and Practice of Sleep Medicine / [ed] Meir H. Kryger, Thomas Roth, William C. Dement, Elsevier, 2016, 6 uppl., p. 742-749Chapter in book (Refereed)
  • 28.
    Lasselin, Julie
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden; University of Duisburg-Essen, Germany.
    Elsenbruch, Sigrid
    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.
    Karshikoff, Bianka
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Grigoleit, Jan-Sebastian
    Engler, Harald
    Schedlowski, Manfred
    Benson, Sven
    Mood disturbance during experimental endotoxemia: Predictors of state anxiety as a psychological component of sickness behavior2016In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 57, p. 30-37Article in journal (Refereed)
    Abstract [en]

    Lipopolysaccharide (LPS) administration is a well-established model to assess afferent immune-to-brain communication and behavioral aspects of inflammation. Nevertheless, only few studies in comparatively small samples have assessed state anxiety as a psychological component of sickness behavior despite possible clinical implications for the pathophysiology of neuropsychiatric conditions. Thus, the goal of the present analyses carried out in a large, pooled dataset from two independent study sites was to analyze the state anxiety response to LPS administration and to investigate predictors (i.e., cytokine changes; pre-existing anxiety and depression symptoms assessed with the Hospital Anxiety and Depression Scale) of the LPS-induced state anxiety changes at different time points after LPS administration. Data from 186 healthy volunteers who participated in one of six randomized, placebo-controlled human studies involving intravenous administration of LPS at doses of 0.4-0.8ng/kg body weight were combined. State anxiety as well as circulating interleukin (IL)-6, tumor necrosis factor (TNF)-α and IL-10 concentrations were significantly increased 2h and 3h after LPS administration, with a peak at 2h, and returned to baseline 6h after administration. Greater changes in IL-6 from baseline to 3h after LPS administration significantly and independently predicted a more pronounced LPS-induced state anxiety response. In addition, higher pre-existing subclinical anxiety symptoms significantly predicted a lower increase in state anxiety 3h and 6h after LPS-administration, which was mediated by TNF-α changes. In conclusion, our findings give additional support for a putative role of inflammatory mechanisms in the pathophysiology of stress-related and anxiety disorders and give new insight on the potential role of pre-existing subclinical affective symptoms.

  • 29.
    Lasselin, Julie
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Ingre, Michael
    Regenbogen, Christina
    Olsson, Mats J.
    Garke, Maria
    Brytting, Mia
    Edgar, Rachel
    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 during naturally occurring respiratory infections: A pilot study2019In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 79, p. 236-243Article in journal (Refereed)
    Abstract [en]

    There is strong experimental support that infections increase the drive for sleep in animals, and it is widely believed that more sleep is part of an adaptive immune response. While respiratory infections (RI) are very prevalent in humans, there is a striking lack of systematic knowledge on how it affects sleep. We recruited 100 people, among whom 28 became sick with an RI during the study period (fulfilling criteria for influenza-like illness, ILI, or acute respiratory infection, ARI). We measured sick participants' sleep at home, both objectively (actigraphy) and subjectively (diary ratings), for one week as well as four weeks later when healthy. During the week with RI, people spent objectively longer time in bed and had a longer total sleep time compared to the healthy week. During the infection, participants also had more awakenings, but no significant differences in sleep latency or sleep efficiency. While sick, people also reported increased difficulties falling asleep, worse sleep quality, more restless sleep and more shallow sleep, while they did not report sleep to be less sufficient. Most problems occurred at the beginning of the sickness week, when symptoms were strong, and showed signs of recovery thereafter (as indicated by interactions between condition and day/night of data collection for all the 10 sleep outcomes). The degree of symptoms of RI was related to a worse sleep quality and more restless sleep, but not to any of the objective sleep outcomes or the other subjective sleep variables. Having a higher body temperature was not significantly related to any of the sleep variables. This study suggests that having a respiratory infection is associated with spending more time in bed and sleeping longer, but also with more disturbed sleep, both objectively and subjectively. This novel study should be seen as being of pilot character. There is a need for larger studies which classify pathogen type and include baseline predictors, or that manipulate sleep, in order to understand whether the sleep alterations seen during infections are adaptive and whether sleep interventions could be used to improve recovery from respiratory infections.

  • 30.
    Lasselin, Julie
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden; Universitätsklinikum Essen, Germany.
    Kemani, Mike K.
    Kanstrup, Marie
    Olsson, Gunnar L.
    Axelsson, John
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Andreasson, Anna
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Wicksell, Rikard K.
    Low-grade inflammation may moderate the effect of behavioral treatment for chronic pain in adults2016In: Journal of behavioral medicine, ISSN 0160-7715, E-ISSN 1573-3521, Vol. 39, no 5, p. 916-924Article in journal (Refereed)
    Abstract [en]

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

  • 31.
    Lasselin, Julie
    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.
    Axelsson, John
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Karshikoff, Bianca
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Engler, H.
    Elsenbruch, S.
    Grigoleit, J.
    Benson, S.
    Pre-existent anxiety symptoms is associated with modified behavioral response during endotoxemia2015In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 49, p. e29-e30Article in journal (Refereed)
    Abstract [en]

    Experimental endotoxin administration is a well-established model to analyze the effect of inflammation on the development of mood impairments. However, it remains unknown from previous studies in comparatively small samples whether pre-existing inter-individual differences modulate the behavioral response during endotoxemia. We addressed this question in the present study using a merged database combining data from multiple studies performed at two study sites. In 286 healthy volunteers who either received low-dose intravenous injection of lipopolysaccharide (LPS, 0.4–0.8 ng/kg, n = 168) or saline (n = 118), plasma concentrations of TNF-alpha and IL-6 were analyzed before and 2, 3.5 and 6 hours post injection together with state anxiety symptoms (STAI). Pre-existent symptoms of anxiety and depression (HADS) were assessed before injection. LPS administration induced an increase in state anxiety 2 hours post injection that was positively correlated with increases in TNF-alpha and IL-6, but not with pre-existent HADS scores (when adjusted for age, sex, BMI, LPS dose, and study design). However, higher levels of pre-existent HADS anxiety symptoms predicted a stronger subsequent reduction in state anxiety at 3.5 and 6 hours post LPS injection. Taken together, these data suggest that although inter-individual differences in anxiety or depression symptoms do not appear to explain the extent of mood impairments during endotoxemia, at least in non-patient samples, they still lead to a modified mood response with a faster and stronger decline.

  • 32.
    Lasselin, Julie
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden; University Hospital Essen, Germany.
    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.
    Karshikoff, Bianka
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden; Stanford University School of Medicine, USA.
    Sex differences in how inflammation affects behavior: What we can learn from experimental inflammatory models in humans2018In: Frontiers in neuroendocrinology (Print), ISSN 0091-3022, E-ISSN 1095-6808, Vol. 50, p. 91-106Article, review/survey (Refereed)
    Abstract [en]

    Human models demonstrate that experimental activation of the innate immune system has profound effects on brain activation and behavior, inducing fatigue, worsened mood and pain sensitivity. It has been proposed that inflammation is a mechanism involved in the etiology and maintenance of depression, chronic pain and long-term fatigue. These diseases show a strong female overrepresentation, suggesting that a better understanding of sex differences in how inflammation drives behavior could help the development of individualized treatment interventions. For this purpose, we here review sex differences in studies using experimental inflammatory models to investigate changes in brain activity and behavior. We suggest a model in which inflammation accentuates sex differences in brain networks and pre-existing vulnerability factors. This effect could render women more vulnerable to the detrimental effects of immune-to-brain communication over time. We call for systematic and large scale investigations of vulnerability factors for women in the behavioral response to inflammation.

  • 33.
    Lasselin, Julie
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden; University Hospital Essen, Germany.
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Paues-Göranson, Sofie
    Olsson, Mats J.
    Axelsson, John
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Communication of health in experimentally sick men and women: A pilot study2018In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 87, p. 188-195Article in journal (Refereed)
    Abstract [en]

    The way people communicate their ill-health and the factors involved in ill-health communication remain poorly known. In the present study, we tested how men and women communicate their sickness and assessed whether sickness-related variables (i.e., body temperature, immune response, subjective sickness symptoms) predicted communicative behaviors. Twenty-two participants were filmed during experimentally induced sickness, triggered by lipopolysaccharide administration (2ng/kg body weight), and after placebo administration, in presence of female care providers. Two trained raters scored participants' communicative behaviors (verbal complaints, moaning and sighs/deep breaths). The physiological and subjective sickness responses were similar in both sexes. Participants were more likely to moan and complain when sick, although the frequency of these behaviors remained low and no clear sex differences was observed. Nevertheless, frequency of sighs/deep breaths was increased amongst sick men but not in women. Sickness-related variables did not predict sigh/deep breath frequency. In this setting, sick men appear to display a lower threshold of expressing their malaise as compared to similarly sick women.

  • 34.
    Lasselin, Julie
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden; University Hospital Essen, Germany.
    Petrovic, Predrag
    Olsson, Mats J.
    Paues Göranson, Sofie
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Jensen, Karin B.
    Axelsson, John
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Sickness behavior is not all about the immune response: Possible roles of expectations and prediction errors in the worry of being sick2018In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 74, p. 213-221Article in journal (Refereed)
    Abstract [en]

    Background

    People react very differently when sick, and there are only poor correlations between the intensity of the immune response and sickness behavior. Yet, alternative predictors of the individual differences in sickness are under-investigated. Based on the predictive coding model of placebo responses, where health outcomes are function of bottom-up sensory information and top-down expectancies, we hypothesized that individual differences in behavioral changes during sickness could be explained by individual top-down expectancies and prediction errors.

    Methods

    Twenty-two healthy participants were made sick by intravenously administering lipopolysaccharide (2 ng/kg body weight). Their expectations of becoming sick were assessed before the injection.

    Results

    Participants having lower expectations of becoming sick before the injection reacted with more emotional distress (i.e., more negative affect and lower emotional arousal) than those with high expectations of becoming sick, despite having similar overall sickness behavior (i.e., a combined factor including fatigue, pain, nausea and social withdrawal). In keeping with a predictive coding model, the “prediction error signal”, i.e., the discrepancy between the immune signal and sickness expectancy, predicted emotional distress (reduction in emotional arousal in particular).

    Conclusion

    The current findings suggest that the emotional component of sickness behavior is, at least partly, shaped by top-down expectations. Helping patients having a realistic expectation of symptoms during treatment of an illness may thus reduce aggravated emotional responses, and ultimately improve patients’ quality of life and treatment compliance.

    Registration

    “Endotoxin-induced Inflammatory and Behavioral Responses and Predictors of Individual Differences”, https://clinicaltrials.gov/ct2/show/NCT02529592, registration number: NCT02529592.

  • 35.
    Lasselin, Julie
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden; Institute of Medical Psychology and Behavioral Immunobiology, Universitätsklinikum Essen, Germany.
    Treadway, Michael T.
    Lacourt, Tamara E.
    Soop, Anne
    Olsson, Mats J.
    Karshikoff, Bianka
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Paues-Göranson, Sofie
    Axelsson, John
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Dantzer, Robert
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Lipopolysaccharide Alters Motivated Behavior in a Monetary Reward Task: a Randomized Trial2017In: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1740-634X, Vol. 42, no 4, p. 801-810Article in journal (Refereed)
    Abstract [en]

    Inflammation-induced sickness is associated with a large set of behavioral alterations; however, its motivational aspects remain poorly explored in humans. The present study assessed the effect of lipopolysaccharide (LPS) administration at a dose of 2 ng/kg of body weight on motivation in 21 healthy human subjects in a double-blinded, placebo (saline)-controlled, cross-over design. Incentive motivation and reward sensitivity were measured using the Effort Expenditure for Rewards Task (EEfRT), in which motivation for high-effort/high-reward trials vs low-effort/low-reward trials are manipulated by variations in reward magnitude and,probability to win. Because of the strong interactions between sleepiness and motivation, the role of sleepiness was also determined. As expected, the probability to win predicted the choice to engage in high-effort/high-reward trials; however, this occurred at a greater extent after LPS than after saline administration. This effect was related to the level of sleepiness. Sleepiness increased motivation to choose the high-effort/high-reward mode of response, but only when the probability to win was the highest. LPS had no effect on reward sensitivity either directly or via sleepiness. These results indicate that systemic inflammation induced by LPS administration causes motivational changes in young healthy subjects, which are associated with sleepiness. Thus, despite its association with energy-saving behaviors, sickness allows increased incentive motivation when the effort is deemed worthwhile.

  • 36.
    Lekander, Mats
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Karshikoff, Bianka
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Johansson, Emilia
    Soop, Anne
    Fransson, Peter
    Lundström, Johan N.
    Andreasson, Anna
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Ingvar, Martin
    Petrovic, Predrag
    Axelsson, John
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Nilsonne, Gustav
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Intrinsic functional connectivity of insular cortex and symptoms of sickness during acute experimental inflammation2016In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 56, p. 34-41Article in journal (Refereed)
    Abstract [en]

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

  • 37.
    Lidberg, Lisa
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Andreasson, Anna N.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Karshikoff, B.
    Axelsson, John
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Olgart Höglund, C.
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Self-rated health in response to experimental manipulations of inflammation is mediated by sickness behavior as assessed by the sickness questionnaire2013In: Brain, Behavior, and Immunity, ISSN 0889-1591, Vol. 32, no Supplement, p. e34-e34Article in journal (Refereed)
    Abstract [en]

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

  • 38. Marraffa, Alexandre
    et al.
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Solsjö, Peter
    Olsson, Mats J.
    Lasselin, Julie
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden; University Hospital Essen, Germany.
    Axelsson, John
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Yawning, a thermoregulatory mechanism during fever? A study of yawning frequency and its predictors during experimentally induced sickness2017In: Physiology and Behavior, ISSN 0031-9384, E-ISSN 1873-507X, Vol. 182, p. 27-33Article in journal (Refereed)
    Abstract [en]

    Yawning has been proposed to serve both physiological and social functions, the latter likely to have developed later in its evolution. A central hypothesis is that yawning cools the brain but whether yawning is a thermoregulatory mechanism that is activated during hyperthermia (i.e., thermoregulatory failure) or is activated in any instance of brain temperature increase (e.g., also during fever) is unclear and experimental assessments of yawning during fever are lacking. In this study, we determined the effect of experimentally induced fever on yawning frequency. We also explored alternative predictors of yawning during sickness (sleepiness, autonomic nervous system indexes and sickness symptoms). Twenty-two healthy human subjects participated in a randomized, placebo-controlled, cross-over study, where the subjects received an injection of the bacterial endotoxin lipopolysaccharide (LPS) at a dose of 2 ng/kg body weight in one condition and placebo in the other. Yawning was scored from video recordings from 30 min before to 4 h after the injection. Body temperature was measured frequently, alongside with heart rate, blood pressure, nausea and overall sickness symptoms. Yawning frequency was found to significantly increase over time during experimentally induced sickness, but not in the placebo condition. In particular, yawning frequency was increased during the rising phase of body temperature induced by LPS administration, although no significant correlation was found between body temperature increase and yawning frequency. In addition, exploratory analyses showed that a higher yawning frequency was associated with less increase in sickness symptoms and nausea intensity. While the current study adds to previous research showing significant increase in yawning frequency during hyperthermia, further studies are needed if we are to properly characterize the brain cooling role of yawning in humans. The investigation of other functions, such as being a vasovagal inhibitory, may shed stronger light on the functions of yawning.

  • 39.
    Nilsonne, Gustav
    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.
    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.
    Ingre, Michael
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Diurnal Variation of Circulating Interleukin-6 in Humans: A Meta-Analysis2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 11, article id e0165799Article in journal (Refereed)
    Abstract [en]

    The pleiotropic cytokine interleukin-6 (IL-6) has been proposed to contribute to circadian regulation of sleepiness by increasing in the blood at night. Earlier studies have reported diurnal variation of IL-6, but phase estimates are conflicting. We have therefore performed a meta-analysis on the diurnal variation of circulating IL-6. Studies were included if they reported IL-6 in plasma or serum recorded at least twice within 24 hours in the same individual. A systematic search resulted in the inclusion of 43 studies with 56 datasets, for a total of 1100 participants. Individual participant data were available from 4 datasets with a total of 56 participants. Mixed-effects meta-regression modelling confirmed that IL-6 varied across the day, the most conspicuous effect being a trough in the morning. These results stand in contrast to earlier findings of a peak in the evening or night, and suggest that diurnal variation should be taken into account in order to avoid confounding by time of day in studies of IL-6 in plasma or serum.

  • 40.
    Petersen, Helena
    et al.
    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.
    D'Onofrio, Paolo
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    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.
    Thank god it's Friday - sleep improved2017In: Journal of Sleep Research, ISSN 0962-1105, E-ISSN 1365-2869, Vol. 26, no 5, p. 567-571Article in journal (Refereed)
    Abstract [en]

    The weekend is usually seen as a window of recovery. Thus, sleep before a day off may be less impaired than that before a workday. However, very few polysomnographical studies have investigated this hypothesis. Therefore, the aim of the present study was to compare sleep before a workday with that before a weekend. Seventeen teachers participated. Sleep was recorded with polysomnography on one weekday night during the workweek, and on a workday (Friday) followed by a day off. Sleep diaries and actigraphs were also used. Weekend sleep showed delayed bedtime and time of rising, a longer total sleep time (45 min), increased N3 and N1, and decreased N2 and REM. Sleep spindles were reduced. The results remained after truncation to the shortest common sleep duration (5 h). The increase in N3 from weekday sleep to Friday night sleep was positively correlated with N1 change (r = 0.853, P <= 0.001), and negatively correlated with N2 change (r = -0.614, P <= 0.001). Subjective ratings showed that weekend sleep was associated with less awakening problems and lower subjective arousal during the day. The authors concluded that weekend sleep was longer, and showed increased N3 and N1. The authors suggest that the N3 increase before the day off is a result of lower stress, while the N1 increase may be an effect of sleep spindle suppression via the increase of N3 (which would suppress sleep spindles), thus reducing N2 and enhancing N1.

  • 41. Pontén, Moa
    et al.
    Fust, Jens
    D'Onofrio, Paolo
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    van Dorp, Rick
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Sunnergård, Linda
    Ingre, Michael
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Institute for Globally Distributed Open Research and Education (IGDORE), Sweden.
    Axelsson, John
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Jensen, Karin
    The pain alarm response - an example of how conscious awareness shapes pain perception2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 12478Article in journal (Refereed)
    Abstract [en]

    Pain is subjective and largely shaped by context, yet, little is known about the boundaries for such influences, in particular in relation to conscious awareness. Here, we investigated processing of noxious stimuli during sleep. Four experiments were performed where participants (n = 114) were exposed to repetitions of noxious heat, either when awake or during sleep. A test-phase followed where participants were awake and exposed to painful stimuli and asked to rate pain. Two control experiments included only the test-phase, without any prior pain exposures. Participants in the awake condition rated all test-phase stimuli the same. Conversely, participants who had been sleeping, and thus unaware of getting noxious heat, displayed heightened pain during the first part of the test-phase. This heightened reaction to noxious stimuli-a pain alarm response-was further pronounced in the control conditions where participants were naive to noxious heat. Results suggest that the pain alarm response is partly dependent on conscious awareness.

  • 42. Regenbogen, C.
    et al.
    Axelsson, John
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Lasselin, Julie
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska institutet, Sverige; Universitätsklinikum Essen, Germany.
    Porada, D.
    Sundelin, Tina
    Stockholm University, Faculty of Social Sciences, Department of Psychology. Karolinska Institutet, Sweden.
    Peter, M.
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska institutet, Sweden.
    Lundström, J. N.
    Olsson, M. J.
    Multisensory detection of sickness2016In: XXVIth Annual Meeting of the European Chemoreception Research Organization: Abstract Book, 2016, p. 94-95Conference paper (Refereed)
    Abstract [en]

    Converging evidence suggests that humans have a behavioral repertoire that assists the immune system in the defense against infectious disease. Behavioral detection of subtle and early sickness cues in others, and subsequent avoidance of the infected conspecific, would indeed be a cost-efficient way of coping with an environment fraught with pathogens. That humans can detect early and subtle cues of sickness by way of both olfaction and vision was recently demonstrated. The current study targeted how sickness cues affect social perception 95and how these visual and olfactory cues, alone and in unison, activate the brain.

  • 43. Regenbogen, Christina
    et al.
    Axelsson, John
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Lasselin, Julie
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden; Universitätsklinikum Essen, Germany.
    Porada, Danja K.
    Sundelin, Tina
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Biological psychology. Karolinska Institutet, Sweden.
    Peter, Moa G.
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institute, Sweden.
    Lundström, Johan N.
    Olsson, Mats J.
    Behavioral and neural correlates to multisensory detection of sick humans2017In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 114, no 24, p. 6400-6405Article in journal (Refereed)
    Abstract [en]

    Throughout human evolution, infectious diseases have been a primary cause of death. Detection of subtle cues indicating sickness and avoidance of sick conspecifics would therefore be an adaptive way of coping with an environment fraught with pathogens. This study determines how humans perceive and integrate early cues of sickness in conspecifics sampled just hours after the induction of immune system activation, and the underlying neural mechanisms for this detection. In a double-blind placebo-controlled crossover design, the immune system in 22 sample donors was transiently activated with an endotoxin injection [lipopolysaccharide (LPS)]. Facial photographs and body odor samples were taken from the same donors when sick (LPS-injected) and when healthy (saline-injected) and subsequently were presented to a separate group of participants (n = 30) who rated their liking of the presented person during fMRI scanning. Faces were less socially desirable when sick, and sick body odors tended to lower liking of the faces. Sickness status presented by odor and facial photograph resulted in increased neural activation of odor-and faceperception networks, respectively. A superadditive effect of olfactory-visual integration of sickness cues was found in the intraparietal sulcus, which was functionally connected to core areas of multisensory integration in the superior temporal sulcus and orbitofrontal cortex. Taken together, the results outline a disease-avoidance model in which neural mechanisms involved in the detection of disease cues and multisensory integration are vital parts.

  • 44. Sarolidou, Georgia
    et al.
    Axelsson, John
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Sundelin, Tina
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden; New York University, USA.
    Lasselin, Julie
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Regenbogen, Christina
    Sorjonen, Kimmo
    Lundström, Johan N.
    Stockholm University, Faculty of Humanities, Department of Linguistics. Karolinska Institutet, Sweden; Monell Chemical Senses Center, USA; University of Pennsylvania, USA.
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Olsson, Mats J.
    Emotional expressions of the sick face2019In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 80, p. 286-291Article in journal (Refereed)
    Abstract [en]

    To handle the substantial threat posed by infectious diseases, behaviors that promote avoidance of contagion are crucial. Based on the fact that sickness depresses mood and that emotional expressions reveal inner states of individuals to others, which in turn affect approach/avoidance behaviors, we hypothesized that facial expressions of emotion may play a role in sickness detection. Using an experimental model of sickness, 22 volunteers were intravenously injected with either endotoxin (lipopolysaccharide; 2 ng/kg body weight) and placebo using a randomized cross-over design. The volunteers were two hours later asked to keep a relaxed expression on their face while their facial photograph was taken. To assess the emotional expression of the sick face, 49 participants were recruited and were asked to rate the emotional expression of the facial photographs of the volunteers when sick and when healthy. Our results indicate that the emotional expression of faces changed two hours after being made temporarily sick by an endotoxin injection. Sick faces were perceived as more sick/less healthy, but also as expressing more negative emotions, such as sadness and disgust, and less happiness and surprise. The emotional expressions mediated 59.1% of the treatment-dependent change in rated health. The inclusion of physical features associated with emotional expressions to the mediation analysis supported these results. We conclude that emotional expressions may contribute to detection and avoidance of infectious individuals and thereby be part of a behavioral defense against disease.

  • 45. Sarolidou, Georgia
    et al.
    Kimball, Bruce A.
    Lasselin, Julie
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden; Universitätsklinikum Essen, Germany.
    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.
    Disease detection: Volatile biomarkers in acute inflammation2017In: Chemical Senses, ISSN 0379-864X, E-ISSN 1464-3553, Vol. 42, no 2, article id P61Article in journal (Refereed)
    Abstract [en]

    Through history, infectious bacteria and viruses have posed a threat to humanity. Being able to detect and avoid pathogens is, therefore, of crucial importance. It has been shown that body odor samples, such as urine, from immune-activated animals contain sickness cues and detection of which, results in avoidance behavior in conspecifics. Perceivable changes in body odor samples have also, recently, been shown in immune-activated human participants. The main aim of this study was to identify potential volatile biomarkers of the acute inflammatory response. Healthy volunteers were injected twice in a crossover design, once with the bacterial endotoxin lipopolysaccharide (LPS, 2ng/kg bw) and once with placebo (saline). LPS caused a transient systemic inflammatory response as shown by pro-inflammatory cytocines, tympanic temperature and subjective sickness ratings (significant interactions between condition and time with all ps<.001, and all ηρ2>.663). Axillary sweat and urine were collected both before and 2–4 hours after injection. Headspace from these samples were analyzed using gas chromatography-mass spectrometry (GC-MS). GC-MS data analyses assessed the differences in the profile of volatile compounds of urine and sweat from LPS and placebo donors. Results regarding possible differences between volatile biomarkers in LPS and placebo condition will be presented and discussed.

  • 46.
    Schwarz, Johanna
    et al.
    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.
    Gerhardsson, Andreas
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Work and organizational psychology.
    Tamm, Sandra
    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.
    Kecklund, Göran
    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.
    Mood impairment is stronger in young than in older adults after sleep deprivation2019In: Journal of Sleep Research, ISSN 0962-1105, E-ISSN 1365-2869, Vol. 28, no 4, article id e12801Article in journal (Refereed)
    Abstract [en]

    Sleep deprivation commonly impairs affective regulation and causes worse mood. However, the majority of previous research concerns young adults. Because susceptibility to sleep deprivation and emotion regulation change distinctively across adult age, we tested here the hypothesis that the effect of sleep deprivation on mood is stronger in young than in older adults. In an experimental design, young (18–30 years) and older adults (60–72 years) participated in either a sleep control (young, n = 63; older, n = 47) or a total sleep deprivation condition (young, n = 61; older, n = 47). Sleepiness, mood and common symptoms of sleep deprivation were measured using established questionnaires and ratings. Sleep‐deprived participants felt more sleepy, stressed and cold, and reported lower vigour and positive affect, regardless of age. All the other outcome measures (negative affect, depression, confusion, tension, anger, fatigue, total mood disturbance, hunger, cognitive attenuation, irritability) showed a weaker response to sleep deprivation in the older group, as indicated by age*sleep deprivation interactions (ps < 0.05). The results show that older adults are emotionally less affected by sleep deprivation than young adults. This tolerance was mainly related to an attenuated increase in negative mood. This could possibly be related to the well‐known positivity effect, which suggests that older adults prioritize regulating their emotions to optimize well‐being. The results also highlight that caution is warranted when generalizing results from sleep deprivation studies across the adult lifespan.

  • 47.
    Schwarz, Johanna
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Gerhardsson, Andreas
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Work and organizational psychology.
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Fischer, Håkan
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Biological psychology.
    Axelsson, John
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Kecklund, Göran
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Åkerstedt, Torbjörn
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Age-dependent effects of sleep deprivation on task performance and mind wandering2017In: Sleep Medicine, ISSN 1389-9457, E-ISSN 1878-5506, Vol. 40, no Suppl. 1, article id e297Article in journal (Refereed)
    Abstract [en]

    Introduction: Mind wandering, the drift of attention from the current task at hand to self-generated thought is commonly associated with poorer performance, and could be a potential pathway through which sleep deprivation affects performance. Little is known about this, however. Therefore, the aim of the present study was to address the effect of sleep deprivation on mind wandering and performance in a sustained attention task. In addition, we studied age as moderating factor, since older individuals are generally less prone to mind wandering.

    Materials and methods: Healthy young (18-30years) and older (60-72years) subjects participated in either a normal night sleep (NSD) or a total sleep deprivation (SD) condition, i.e. 4 conditions: NSD (n=31), SD (n=30), NSDold (n = 24), SDold (n= 24). Performance was measured using the Sustained Attention to Response Task, during which 10 thought probes were included that prompted the subjects to answer a question on what they were you just thinking about, using predefined answer alternatives. Mind wandering was quantified as occurrence of task-unrelated thoughts.

    Results: Applying a 2 (age) X 2 (sleep deprivation) ANOVA, significant main effects for sleep deprivation and age were observed for omissions, indicating worse performance after sleep deprivation and in young participants (p's < .05). These main effects were dominated by an age*sleep deprivation interaction (p = .04), which was due to sleep deprivation causing significantly more omission errors in young subjects (Mean ±SEM; NSD: 2.3 ±0.9; SD: 13.1 ±4.1) but not in older subjects (NSDold: 1.9 ±0.4; SDold: 2.8 ±0.9).

    Likewise, main and interaction effects for age and sleep deprivation were significant for task-unrelated thoughts (p's < 0.01). Task unrelated thoughts were significantly more frequent after sleep loss in young (NSD: 1.5 ±0.2; SD: 4.3 ±0.6), but not older subjects (NSDold: 0.3 ±0.2; SDold: 0.5 ±0.2) (interaction age*sleep deprivation p < .01). Young subjects had significantly more task-unrelated thoughts than older, regardless of sleep condition.

    Task-unrelated thoughts correlated with errors of omission (r = 0.65, p < .001). Also, including task unrelated thoughts as covariate in the age * sleep deprivation ANOVA, main and interactions effect of age and sleep deprivation were no longer significant.

    Reaction time was significantly slower in older adults, but no main or interaction effect of sleep deprivation occurred. Errors of commission were not affected by condition.

    Conclusions: The results show that sleep deprivation caused both mind wandering and poorer task performance in young but not older participants. In addition, mind wandering rates correlated with errors of omission, which may indicate that a diminished ability to shut down off-task thoughts after sleep deprivation could be an important pathway to performance decrements after sleep loss. In line with previous research, mind wandering appears to occur less frequently in older individuals compared with younger. This lower occurrence of mind wandering in older subjects may potentially enable them to better maintain performance after sleep deprivation and partially explain the higher resilience of older adults to sleep deprivation.

  • 48.
    Schwarz, Johanna
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Gerhardsson, Andreas
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Van Leeuwen, Wessel
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    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. Karolinska Institutet, Sweden.
    Åkerstedt, Torbjörn
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    The effect of sleep loss on the response to acute psychosocial stress in young and elderly2016Conference paper (Refereed)
    Abstract [en]

    Both sleep loss and social stress are risk factors for health and performance ability. It is assumed that sleep and stress are bidirectional linked, but most of the previous research has focused on studying sleep problems as consequence of stress. We believe that it is important to improve our understanding of the reverse connection, which is less studied. This presentation will cover recent experimental human studies that have investigated how sleep loss affects stress responses and whether it makes individuals more vulnerable to psychosocial stress. A study by Minkel et al. (Health Psychology, 2014) reported that the cortisol response to an acute stress situation was increased after sleep deprivation compared with a control condition indicating a more pronounced activation of the hypothalamic-pituitary-adrenal stress axis. I will also present recently collected data from young (18–30 years) and older (60–72 years) subjects that participated in four conditions (between subject design):

    (i) normal night sleep.

    (ii) normal night sleep & acute stress (Trier Social Stress Test).

    (iii) total sleep deprivation.

    (iv) total sleep deprivation & acute stress.

    The presentation thus provides state of the art knowledge of the link between sleep loss and vulnerability to stress.

  • 49. Stothard, Ellen R.
    et al.
    McHill, Andrew W.
    Depner, Christopher M.
    Birks, Brian R.
    Moehlman, Thomas M.
    Ritchie, Hannah K.
    Guzzetti, Jacob R.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Chinoy, Evan D.
    LeBourgeois, Monique K.
    Axelsson, John
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Wright, Kenneth P.
    Circadian Entrainment to the Natural Light-Dark Cycle across Seasons and the Weekend2017In: Current Biology, ISSN 0960-9822, E-ISSN 1879-0445, Vol. 27, no 4, p. 508-513Article in journal (Refereed)
    Abstract [en]

    Reduced exposure to daytime sunlight and increased exposure to electrical lighting at night leads to late circadian and sleep timing [1-3]. We have previously shown that exposure to a natural summer 14 hr 40 min:9 hr 20 min light-dark cycle entrains the human circadian clock to solar time, such that the internal biological night begins near sunset and ends near sunrise [1]. Here we show that the beginning of the biological night and sleep occur earlier after a week's exposure to a natural winter 9 hr 20 min:14 hr 40 min light-dark cycle as compared to the modern electrical lighting environment. Further, we find that the human circadian clock is sensitive to seasonal changes in the natural light-dark cycle, showing an expansion of the biological night in winter compared to summer, akin to that seen in non-humans [4-8]. We also show that circadian and sleep timing occur earlier after spending a weekend camping in a summer 14 hr 39 min:9 hr 21 min natural light-dark cycle compared to a typical weekend in the modern environment. Weekend exposure to natural light was sufficient to achieve similar to 69% of the shift in circadian timing we previously reported after a week's exposure to natural light [1]. These findings provide evidence that the human circadian clock adapts to seasonal changes in the natural light-dark cycle and is timed later in the modern environment in both winter and summer. Further, we demonstrate that earlier circadian timing can be rapidly achieved through natural light exposure during a weekend spent camping.

  • 50.
    Sundelin, Tina
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Axelsson, John
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Sleep loss negatively affects employability and perceived leadership skills2014In: Journal of Sleep Research, Special issue: 22nd Congress of the European Sleep Research Society, 16-20 September 2014, Tallinn, Estonia, 2014Conference paper (Other academic)
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