A selection from Stockholm University publication database

• Characterization of exhaustion disorder and identification of outcomes that matter to patients: Qualitative content analysis of a Swedish national online survey

  2023. Elin Lindsäter (et al.). Stress and Health 39 (4), 813-827

  Article

  Fatigue is a common presenting problem in healthcare settings, often attributed to chronic psychosocial stress. Understanding of fatigue and development of evidence-based treatments is hampered by a lack of consensus regarding diagnostic definitions and outcomes to be measured in clinical trials. This study aimed to map outcome domains of importance to the Swedish diagnosis stress-induced exhaustion disorder (ED; ICD-10, code F43.8 A). An online survey was distributed nationwide in Sweden to individuals who reported to have been diagnosed with ED and to healthcare professionals working with ED patients. To identify outcome domains, participants replied anonymously to four open-ended questions about symptoms and expectations for ED-treatment. Qualitative content analysis was conducted of a randomized subsample of respondents, using a mathematical model to determine data saturation. Six hundred seventy participants (573 with reported ED, 97 healthcare professionals) completed the survey. Qualitative content analysis of answers supplied by 105 randomized participants identified 87 outcomes of importance to ED encompassing physical, cognitive, and emotional symptoms as well as functional disability. Self-rating scales indicated that many ED participants, beyond reporting fatigue, also reported symptoms of moderate to severe depression, anxiety, insomnia, poor self-rated health, and sickness behavior. This study presents a map of outcome domains of importance for ED. Results shed light on the panorama of issues that individuals with ED deal with and can be used as a step to further understand the condition and to reach consensus regarding outcome domains to measure in clinical trials of chronic stress and fatigue. Preregistration: Open Science Framework (osf.io) with DOI https://doi.org/10.17605/OSF.IO/4VUAG

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• Discriminating between sick and healthy faces based on early sickness cues: an exploratory analysis of sex differences

  2023. Arnaud Tognetti (et al.). Evolution, Medicine, and Public Health 11 (1), 386-396

  Article

  Background and objectives: It has been argued that sex and disease-related traits should influence how observers respond to sensory sickness cues. In fact, there is evidence that humans can detect sensory cues related to infection in others, but lack of power from earlier studies prevents any firm conclusion regarding whether perception of sickness cues is associated with sex and disease-related personality traits. Here, we tested whether women (relative to men), individuals with poorer self-reported health, and who are more sensitive to disgust, vulnerable to disease, and concerned about their health, overestimate the presence of, and/or are better at detecting sickness cues.

  Methodology: In a large online study, 343 women and 340 men were instructed to identify the sick faces from a series of sick and healthy photographs of volunteers with an induced acute experimental inflammation. Participants also completed several disease-related questionnaires.

  Results: While both men and women could discriminate between sick and healthy individuals above chance level, exploratory analyses revealed that women outperformed men in accuracy and speed of discrimination. Furthermore, we demonstrated that higher disgust sensitivity to body odors is associated with a more liberal decision criterion for categorizing faces as sick.

  Conclusion: Our findings give strong support for the human ability to discriminate between sick and healthy individuals based on early facial cues of sickness and suggest that women are significantly, although only slightly, better at this task. If this finding is replicated, future studies should determine whether women’s better performance is related to increased avoidance of sick individuals.

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• Disgusting odors trigger the oral immune system

  2023. Stephanie Anja Juran (et al.). Evolution, Medicine, and Public Health 11 (1), 8-17

  Article

  Recent research has characterized the behavioral defense against disease. In particular the detection of sickness cues, the adaptive reactions (e.g. avoidance) to these cues and the mediating role of disgust have been the focus. A presumably important but less investigated part of a behavioral defense is the immune system response of the observer of sickness cues. Odors are intimately connected to disease and disgust, and research has shown how olfaction conveys sickness cues in both animals and humans. This study aims to test whether odorous sickness cues (i.e. disgusting odors) can trigger a preparatory immune response in humans. We show that subjective and objective disgust measures, as well as TNFα levels in saliva increased immediately after exposure to disgusting odors in a sample of 36 individuals. Altogether, these results suggest a collaboration between behavioral mechanisms of pathogen avoidance in olfaction, mediated by the emotion of disgust, and mechanisms of pathogen elimination facilitated by inflammatory mediators.

  Disgusting stimuli are associated with an increased risk of infection. We here test whether disgusting odors, can trigger an immune response in the oral cavity. The results indicate an increase level of TNFα in the saliva. This supports that disease cues can trigger a preparatory response in the oral cavity.

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• Disturbed sleep and patterns of psychiatric symptoms and function in a school-based sample of adolescents

  2023. Lie Åslund (et al.). Clinical Child Psychology and Psychiatry 28 (4), 1524-1535

  Article

  Background Sleep problems are common in adolescence and often related to psychopathology and impaired functioning. However, most studies have used summative scores, and little is known about how adolescents with disrupted sleep perceive their specific symptoms and dysfunctions. This study explored differences in levels of psychiatric symptoms and functional ability between Swedish adolescents with and without self-reported disturbed sleep in a school-based sample.

  Methods Swedish adolescents (n = 618, mean age 15.7+/-1.9yrs) answered the PROMIS pediatric measures for fatigue, anxiety, depression, pain interference, anger, physical activity and peer and family relationships. Logistic regression analyses were performed to assess differences between respondents with and without disturbed sleep.

  Results Disturbed sleep was associated with higher levels of symptoms of fatigue, anxiety, depression, anger and pain interference, as well as lower functional abilities in terms of physical activity and peer- and family relationships. Adolescents reporting disturbed sleep generally displayed a pattern of impaired executive functioning, internal emotional distress and school- and sleep related worry and dysfunction, as compared to physical disability, aggressive behavior, stress and generalized worry.

  Conclusions The present study adds to the understanding of how disturbed sleep and specific psychiatric symptoms and functional ability are interrelated, which may also have clinical implications.

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• Human scent as a first-line defense against disease

  2023. Amy R. Gordon (et al.). Scientific Reports 13 (1)

  Article

  Individuals may have a different body odor, when they are sick compared to healthy. In the non-human animal literature, olfactory cues have been shown to predict avoidance of sick individuals. We tested whether the mere experimental activation of the innate immune system in healthy human individuals can make an individuals' body odor be perceived as more aversive (intense, unpleasant, and disgusting). Following an endotoxin injection (lipopolysaccharide; 0.6 ng/kg) that creates a transient systemic inflammation, individuals smelled more unpleasant compared to a placebo group (saline injection). Behavioral and chemical analyses of the body odor samples suggest that the volatile components of samples from sick individuals changed qualitatively rather than quantitatively. Our findings support the hypothesis that odor cues of inflammation in axillary sweat are detectable just a few hours after experimental activation of the innate immune system. As such, they may trigger behavioral avoidance, hence constituting a first line of defense against pathogens of infected conspecifics.

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• Humans can detect axillary odor cues of an acute respiratory infection in others

  2023. Arnaud Tognetti (et al.). Evolution medicine and public health 11 (1), 219-228

  Article

  Background and objectives Body odor conveys information about health status to conspecifics and influences approach-avoidance behaviors in animals. Experiments that induce sickness in otherwise healthy individuals suggest that humans too can detect sensory cues to infection in others. Here, we investigated whether individuals could detect through smell a naturally occurring acute respiratory infection in others and whether sickness severity, measured via body temperature and sickness symptoms, was associated with the accuracy of detection. Methodology Body odor samples were collected from 20 donors, once while healthy and once while sick with an acute respiratory infection. Using a double-blind, two-alternative forced-choice method, 80 raters were instructed to identify the sick body odor from paired sick and healthy samples (i.e. 20 pairs). Results Sickness detection was significantly above chance, although the magnitude of the effect was low (56.7%). Raters' sex and disgust sensitivity were not associated with the accuracy of sickness detection. However, we find some indication that greater change in donor body temperature, but not sickness symptoms, between sick and healthy conditions improved sickness detection accuracy. Conclusion and implications Our findings suggest that humans can detect individuals with an acute respiratory infection through smell, albeit only slightly better than chance. Humans, similar to other animals, are likely able to use sickness odor cues to guide adaptive behaviors that decrease the risk of contagion, such as social avoidance. Further studies should determine how well humans can detect specific infections through body odor, such as Covid-19, and how multisensory cues to infection are used simultaneously. Lay Summary Researchers suggest humans evolved the ability to detect sickness in others, facilitating behavioral responses to reduce contagion risk, such as the avoidance of sick individuals. Our study suggests that humans can distinguish healthy from sick individuals with a naturally occurring respiratory infection by smelling body odors, but with limited accuracy.

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• Inflammatory Blood Signature Related to Common Psychological Comorbidity in Chronic Pain

  2023. Bianka Karshikoff (et al.). Biomedicines 11 (3)

  Article

  Chronic pain is characterized by high psychological comorbidity, and diagnoses are symptom-based due to a lack of clear pathophysiological factors and valid biomarkers. We investigate if inflammatory blood biomarker signatures are associated with pain intensity and psychological comorbidity in a mixed chronic pain population. Eighty-one patients (72% women) with chronic pain (>6 months) were included. Patient reported outcomes were collected, and blood was analyzed with the Proseek Multiplex Olink Inflammation Panel (Bioscience Uppsala, Uppsala, Sweden), resulting in 77 inflammatory markers included for multivariate data analysis. Three subgroups of chronic pain patients were identified using an unsupervised principal component analysis. No difference between the subgroups was seen in pain intensity, but differences were seen in mental health and inflammatory profiles. Ten inflammatory proteins were significantly associated with anxiety and depression (using the Generalized Anxiety Disorder 7-item scale (GAD-7) and the Patient Health Questionnaire (PHQ-9): STAMBP, SIRT2, AXIN1, CASP-8, ADA, IL-7, CD40, CXCL1, CXCL5, and CD244. No markers were related to pain intensity. Fifteen proteins could differentiate between patients with moderate/high (GAD-7/PHQ-9 > 10) or mild/no (GAD-7/PHQ-9 < 10) psychological comorbidity. This study further contributes to the increasing knowledge of the importance of inflammation in chronic pain conditions and indicates that specific inflammatory proteins may be related to psychological comorbidity.

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• Internet-delivered cognitive behavioral therapy for adolescents with insomnia: Feasibility and preliminary efficacy

  2023. Li Åslund (et al.). Clinical Child Psychology and Psychiatry

  Article

  Background Insomnia is common in adolescents. This study evaluated feasibility and preliminary efficacy of a six-week internet-delivered cognitive-behavioral therapy for insomnia (ICBT-I) in adolescents.

  Methods In this uncontrolled pilot study, participants (n = 27, 78% female) completed assessments pre- and post intervention. Data on recruitment, adherence to treatment, treatment activity, satisfaction and credibility was collected to assess feasibility. Self-reported insomnia symptoms, sleep parameters as well as depression, anxiety and daytime function were also assessed.

  Results Participants showed good adherence to treatment and found the intervention overall credible and satisfactory. From pre- to post-assessment, statistically significant improvements were found for insomnia symptoms (p < .001; d = 1.02), sleep onset latency (p < .001; d = .39), wake after sleep onset (p = .001; d = .34), sleep efficiency (p < .001; d = .5) and depression (p = .01, d = .37). Changes in scores of total sleep time, generalized anxiety, daytime sleepiness and functional disability were not significant.

  Conclusions The present study indicates that ICBT-I is well accepted by adolescents, that insomnia symptoms and sleep parameters can improve following the intervention, and that co-morbid symptoms of depression can be reduced. Due to the limited sample size and the uncontrolled design, the suggested results need to be replicated in well-powered controlled clinical trials.

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• Lipopolysaccharide-induced changes in the kynurenine pathway and symptoms of sickness behavior in humans

  2023. Leonie J. T. Balter (et al.). Psychoneuroendocrinology 153

  Article

  Metabolites of the kynurenine pathway are hypothesized to be implicated in inflammation-associated depression, but there is a lack of experimental studies in humans assessing the kinetics of kynurenine metabolites in relation to experimentally-induced sickness. The aim of the present study was to assess changes in the kynurenine pathway and to explore its relation to symptoms of sickness behavior during an acute experimental immune challenge.

  This double-blind placebo-controlled randomized cross-over study included 22 healthy human participants (n = 21 both sessions, M_age = 23.4, SD = 3.6, nine women) who received an intravenous injection of 2.0 ng/kg lipopolysaccharide (LPS) and saline (placebo) on two different occasions in a randomized order. Blood samples (0 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 5 h, 7 h post-injection) were analyzed for kynurenine metabolites and inflammatory cytokines. The intensity of symptoms of sickness behavior was assessed using the 10-item Sickness Questionnaire at 0 h, 1.5 h, 3 h, 5 h, and 7 h post-injection.

  LPS induced significantly lower concentrations of plasma tryptophan (at 2 h, 4 h, 5 h, and 7 h post-injection), kynurenine (at 2 h, 3 h, 4 h, and 5 h post-injection), nicotinamide (at 4 h, 5 h, and 7 h post-injection), and higher levels for quinolinic acid at 5 h post-injection as compared to placebo. LPS did not affect kynurenic acid, 3-hydroxykynurenine, and picolinic acid. The development of the sickness symptoms was largely similar across items, with the highest levels around 1.5–3 h post-injection. Changes in plasma levels of kynurenine metabolites seem to coincide rather than precede or follow changes in subjective sickness. Exploratory analyses indicate that higher Sickness Questionnaire total scores at 1.5–5 h post-injection were correlated with lower kynurenic acid and nicotinamide levels.

  These results lend further support for LPS-induced changes in the kynurenine pathway, but may not, as interpreted from blood levels, causally link to LPS-induced acute symptoms of sickness behavior. Future research may consider a larger sample to further scrutinize the role of the kynurenine pathway in the sickness response.

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• Mental health, stress, and well-being measured before (2019) and during (2020) COVID-19: a Swedish socioeconomic population-based study

  2023. Ann-Sophie Lindqvist Bagge (et al.). Psychology and Health

  Article

  Objectives: Compare mental health, stress, and well-being in the Swedish population as measured before and during the COVID-19 pandemic. Methods: Repeated cross-sectional design using data measured before (Jan-2019; n = 2791) and during (Oct/Nov-2020; n = 2926) COVID-19 pandemic in Swedish population-representative cohorts. Following constructs were measured: anxiety (Beck Anxiety Inventory), depression (Beck Depression Inventory-II), stress (Perceived Stress Scale-10 items), health-related quality of life (HRQOL[Functional Assessment of Cancer Therapy-General Population]) and self-rated health (SRH) was assessed with a single-item question. Results: When adjusting for age, sex, education, and income there were significantly higher levels of anxiety (M = 9.15 vs. 8.48, p < 0.01) and depression (M = 3.64 vs. 3.30, p = 0.03), lower levels of stress (M = 14.06 vs. 14.91, p < 0.001), but worsened HRQOL (M = 76.40 vs. 77.92, p < 0.01) and SRH (M = 6.91 vs. 7.20, p < 0.001), observed in 2020 compared to 2019. For the negative effects seen in anxiety, depression, HRQOL, and SRH, higher income and education had a protective effect. The decrease in stress was also correlated with higher income. Conclusions: The COVID-19 pandemic led to a small but significant worsening in mental health and well-being in the general Swedish population, where higher socioeconomic status seemed to have a protective effect.

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• Objective cognitive functioning in patients with stress-related disorders: a cross-sectional study using remote digital cognitive testing

  2023. Ludwig Franke Föyen (et al.). BMC Psychiatry 23 (1)

  Article

  Background Patients with stress-related mental disorders often report cognitive impairment, but studies investigating objective cognitive impairment in patients with stress-related disorders have produced inconsistent findings. Aim The primary aim of this study was to investigate objective cognitive functioning in patients diagnosed with the stress-related disorders adjustment disorder or exhaustion disorder, compared to a healthy normative group. Secondary aims were to conduct subgroup analyses of cognitive functioning between the diagnostic groups and explore associations between self-reported symptoms and cognitive functioning. Methods Cognitive test results on a digitally self-administered cognitive test battery from 266 patients (adjustment disorder, n = 131; exhaustion disorder, n = 135) were cross-sectionally compared with results from a healthy normative group (N = 184 to 692) using one-tailed t-tests. ANOVAs were conducted for subgroup analyses, and regression analyses for associations between self-reported symptoms and cognitive functioning. Effect sizes were calculated. Results Patients performed significantly worse than the normative group on all measures with small to moderate effect sizes ranging from d =-.13 to-.57. Those diagnosed with exhaustion disorder performed worse than norms on more measures than did patients with adjustment disorder, but no significant differences between diagnostic groups were found on any measure. Self-reported memory impairment was weakly associated with one of two memory measures. No clear associations between self-reported burnout symptoms and objective cognitive functioning were found. Conclusions This study adds to the literature indicative of small to moderate objective cognitive impairments in patients diagnosed with stress-related mental disorders. Further exploration into mechanisms of cognitive functioning in different populations is needed for development of theoretical models that may explain the weak correlation between self-reported symptoms and objective measures.

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• Olfactory Cues of Naturally Occurring Systemic Inflammation: A Pilot Study of Seasonal Allergy 

  2023. Arnaud Tognetti (et al.). Neuroimmunomodulation 30 (1), 338-345

  Article

  Introduction: In an attempt to avoid contact with infectious individuals, humans likely respond to generalized rather than specific markers of disease. Humans may thus perceive a noninfectious individual as socially less attractive if they look (e.g., have facial discolouration), move (e.g., have a slower walking pace), or sound (e.g., sneeze) sick. This pilot study tested whether humans are averse to the body odour of noninfectious individuals with a low-grade systemic inflammation. Methods: We collected the axillary body odour of individuals with severe seasonal allergy (N = 14) and healthy controls (N = 10) during and outside the allergy season and measured serum levels of two inflammatory cytokines (tumour necrosis factor-α and interleukin-5). Independent participants (N = 67) then sampled and rated these odours on intensity and pleasantness. Results: While individuals with seasonal allergy had nominally more unpleasant and intense body odours during the allergy season, relative to outside the allergy season and to healthy controls, these effects were not significant. When examining immune markers, the change in perceived pleasantness of an individual’s body odour (from out-to-inside pollen season) was significantly related to the change in their interleukin-5 levels but not to tumour necrosis factor-α. Discussion: Our findings tentatively suggest that the human olfactory system could be sensitive to inflammation as present in a noncommunicable condition. Larger replications are required to determine the role of olfaction in the perception of infectious and noninfectious (e.g., chronic diseases) conditions.

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• Baseline Pro-Inflammatory Cytokine Levels Moderate Psychological Inflexibility in Behavioral Treatment for Chronic Pain

  2022. Bianka Karshikoff (et al.). Journal of Clinical Medicine 11 (9)

  Article

  Background: The medical and scientific communities struggle to understand chronic pain and find effective treatments. Multimodal approaches are encouraging but show significant individual differences. Methods: Seventy-eight persons (56 women) with chronic pain received Acceptance and Commitment Therapy and provided blood samples before and after treatment. The participants completed surveys with the blood sampling. Blood plasma was analyzed for IL-6 and TNF-α levels with the Olink Inflammation Panel (Olink Bioscience Uppsala, Sweden). The treatment effects and moderating effects of low-grade inflammation on changes in outcomes were analyzed using linear mixed models. Results: Pain interference (p < 0.001) and psychological inflexibility (p < 0.001) improved significantly during treatment, but pain intensity did not (p = 0.078). Cytokine levels did not change over the course of the treatment (IL-6/TNF-α p = 0.086/0.672). Mean baseline levels of IL-6 and TNF-α moderated improvement in psychological inflexibility during the course of treatment (p = 0.044), but cytokine levels did not moderate changes in pain interference (p = 0.205) or pain intensity (p = 0.536). Conclusions: Higher baseline inflammation levels were related to less improvement in psychological inflexibility. Low-grade inflammation may be one factor underlying the variability in behavioral treatment in chronic pain.

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• COVID-19 related distress in the Swedish population: Validation of the Swedish version of the COVID Stress Scales (CSS)

  2022. Anders Carlander (et al.). PLOS ONE 17 (2)

  Article

  Background

  The COVID Stress Scales (CSS) assess health- and contamination-related distress in the face of a medical outbreak like the ongoing COVID-19 pandemic. Though the CSS is translated into 21 languages, it has not been validated in a Swedish national sample.

  Aim

  Our general objective is to provide a translation, replication, and validation of the CSS and test its convergent- and discriminant validity in relation to anxiety, health anxiety, depression, and stress in the general Swedish population. We also present latent psychometric properties by modelling based on item response theory.

  Methods

  Participants consisted of 3044 Swedish adults (> 18 years) from a pre-stratified (gender, age, and education) sample from The Swedish Citizen Panel. Mental health status was assessed by validated instruments, including the CSS, PHQ-4, SHAI-14, and PSS-10.

  Results

  Results indicate that our Swedish translation of CSS has good psychometric properties and consists of 5 correlated factors.DiscussionThe CSS is useful either as a unidimensional or multidimensional construct using the CSS scales to measure key facets of pandemic-related stress.

  Conclusions

  The findings support the cross-cultural validity of the CSS and its potential utility in understanding many of the emotional challenges posed by the current and future pandemics.

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• DN Debatt: "De utmattade måste få tillgång till rätt vård"

  2022. Christian Rück (et al.). Dagens Nyheter

  Article

  Nio forskare: Kunskapsbristerna som fanns vid införandet av diagnosen utmattningssyndrom är fortfarande lika stora. Nya kriterier håller nu på att tas fram utan att de först har utvärderats vetenskapligt.

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• Editorial: Vulnerability and protective factors for inflammation-associated somatoform and mental disorders

  2022. Bianka Karshikoff, Mats Lekander, Julie Lasselin. Brain, behavior, and immunity 106, 227-230

  Article

  Over the past 30 years, research in psychoneuroimmunology and immunopsychiatry points to immune processes playing a part in the development and maintenance of various non-communicable disorders, including chronic pain (Grace et al., 2014), chronic fatigue (Lacourt et al., 2018), depression (Zunszain et al., 2013), anxiety (Michopoulos et al., 2016), psychosis (Ullah et al., 2021) and neurodegeneration (Park et al., 2020). Many of these disorders are characterized by a complex symptomatology, various comorbidities, and a difficulty to treat the disorder satisfactorily. Although recent research shows that immune alterations and inflammatory components may contribute to the pathophysiology of these diseases, inflammation is probably not sufficient to independently induce these disorders or maintain them. Not all individuals with a heightened inflammatory activity will develop one of these disorders, and some individuals with these disorders show no changes in immune parameters. This suggests the involvement of additional factors that interact with the immune system to cause vulnerability to, or a protection against, inflammation-associated disorders.

  In this special issue of Brain, Behavior and Immunity, we welcomed articles investigating predictors and moderators of inflammation-associated disorders, comorbidities, and behavioral changes. The studies included in this issue range from experimental human and animal studies to clinical investigations applying proteomic approaches. The disorders discussed include those related to aging and neurodegenerative diseases, psychiatric disorders, fatigue, and pain. The authors contributing to this special issue tackle some fundamental questions, including: Why do not all individuals with a heightened inflammatory activity develop one of these disorders? How can we protect against the neuropsychiatric effects of inflammation? Does inflammation interact with other pathological processes of clinical conditions such as Parkinson’s disease and Alzheimer’s disease?

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• Exhaustion disorder: scoping review of research on a recently introduced stress-related diagnosis

  2022. Elin Lindsäter (et al.). BJPsych Open 8 (5)

  Article

  Background

  Symptoms related to chronic stress are prevalent and entail high societal costs, yet there is a lack of international consensus regarding diagnostics and treatment. A new stress-related diagnosis, exhaustion disorder, was introduced into the Swedish version of ICD-10 in 2005. Since then, use of the diagnosis has increased rapidly.

  Aims

  To create the first comprehensive synthesis of research on exhaustion disorder to report on the current state of knowledge. Preregistration: Open Science Framework (osf.io), doi 10.17605/OSF.IO/VFDKW.

  Method

  A PRISMA-guided scoping review of all empirical studies of exhaustion disorder was conducted. Searches were run in the MEDLINE, PsycInfo and Web of Science databases. Data were systematically charted and thematically categorised based on primary area of investigation.

  Results

  Eighty-nine included studies were sorted into six themes relating to lived experience of exhaustion disorder (n = 9), symptom presentation and course (n = 13), cognitive functioning (n = 10), biological measures (n = 24), symptom measurement scales (n = 4) and treatment (n = 29). Several studies indicated that individuals with exhaustion disorder experience a range of psychiatric and somatic symptoms beyond fatigue, but robust findings within most thematic categories were scarce. The limited number of studies, lack of replication of findings and methodological limitations (e.g. small samples and scarcity of specified primary outcomes) preclude firm conclusions about the diagnostic construct.

  Conclusions

  More research is needed to build a solid knowledge base for exhaustion disorder. International collaboration regarding the conceptualisation of chronic stress and fatigue is warranted to accelerate the growth of evidence.

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• Influence of work ability and smoking on the prognosis of long-duration activity-limiting neck/back pain: a cohort study of a Swedish working population

  2022. Tony Bohman (et al.). BMJ Open 12 (4)

  Article

  Objectives Long-duration activity-limiting neck/back pain is common, but the knowledge of what work and lifestyle factors that influence the prognosis is sparse. The objective was therefore to evaluate if two factors, good self-perceived work ability and no daily smoking, are associated with a favourable prognosis of long-duration activity-limiting neck/back pain in a working population, and if these exposures have a synergistic prognostic effect.

  Design A prospective cohort study based on three subsamples from the Stockholm Public Health Cohort.

  Settings A working population in Stockholm County, Sweden.

  Participants Individuals, 18–61 years old, reporting long-duration activity-limiting neck/back pain the previous 6 months at baseline in 2010 (n=5177).

  Measures The exposures were: self-perceived work ability (categorised into good, moderate and poor) and daily smoking (no/yes). The outcome in 2014 was ‘absence of long-duration activity-limiting neck/back pain’ the previous 6 months representing a favourable prognosis of reported problems at baseline in 2010. Risk ratios (RRs) and risk differences (RDs) with 95% CI was estimated by general linear regressions, and the synergistic effect was estimated by the synergy index (SI) with 95% CI.

  Results Participants with moderate or good work ability, respectively, had an adjusted RR for a favourable prognosis of 1.37 (95% CI 1.11 to 1.69), and 1.80 (1.49 to 2.17) in comparison with participants with poor work ability. The corresponding adjusted RD were 0.07 (0.02 to 0.11) and 0.17 (0.12 to 0.22). Participants not smoking on daily basis had an adjusted RR of 1.21 (1.02 to 1.42), and an adjusted RD of 0.05 (0.01 to 0.10) for a favourable outcome compared with daily smokers. The adjusted SI was 0.92 (0.60 to 1.43).

  Conclusion For participants with long-duration activity-limiting neck/back pain, moderate or good self-perceived work ability and not being a daily smoker were associated with a favourable prognosis but having both exposures seemed to have no synergistic prognostic effect.

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• No evidence for transmission of psychosis, bipolar or depressive disorder via hematopoietic stem cell transplantation: A Swedish registry study

  2022. L. D. Ekström (et al.). Psychiatry and Clinical Neurosciences 76 (10), 526-527

  Article

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• The Inflamed Feeling: The Brain's Role in Immune Defence

  2022. Mats Lekander.

  Book

  What do wanting to stay in bed, feeling sick, and being afraid of strangers have in common? The answer is that these feelings can reflect a drive which evolved in our ancestors to combat the threat of infection to survival. Listening to the body's message to the brain that you are sick allows you to save energy that can be used for recuperation and recovery. Urges of staying still, noticing pain, feeling sorry for yourself, and focusing inward are thus bodily messages that benefit the immune defense. Similarly, superficial signs of ill health in others, or even the prejudicial idea of a person with a foreign bacterial culture, can cause anxiety and avoidance as part of the defense strategy. Being at a life or death juncture, your brain and your immune system join forces to preserve or regain health. Having a too high or too low sensitivity to inner or outer disease signals is therefore connected to a risk for mental as well as somatic disorders. In this book, Mats Lekander explains the science behind perceived health, using an arsenal of Barbie dolls, visual illusions, personal experiences, placebo, hypochondriacs, and historical anecdotes against a backdrop of the latest neuroscience and psychoneuroimmunology (the science of the brain, behavior, and immunity). He describes when he poisoned himself at work and enjoyed it, and why white blood cells and inflammation are key players when our brains try to guess what is going on in our inner worlds. 

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• Anterior insula morphology and vulnerability to psychopathology-related symptoms in response to acute inflammation

  2022. Kristoffer N. T. Månsson (et al.). Brain, behavior, and immunity 99, 9-16

  Article

  Introduction: The role of inflammation in common psychiatric diseases is now well acknowledged. However, the factors and mechanisms underlying inter-individual variability in the vulnerability to develop psychopathology related symptoms in response to inflammation are not well characterized. Herein, we aimed at investigating morphological brain regions central for interoception and emotion regulation, and if these are associated with acute inflammation-induced sickness and anxiety responses.

  Methods: Systemic inflammation was induced using an intravenous injection of lipopolysaccharide (LPS) at a dose of 0.6 ng/kg body weight in 28 healthy individuals, while 21 individuals received an injection of saline (placebo). Individuals' gray matter volume was investigated by automated voxel-based morphometry technique on T1-weighted anatomical images derived from magnetic resonance imaging (MRI). Plasma concentrations of TNF alpha and IL-6, sickness symptoms (SicknessQ), and state anxiety (STAI-S) were measured before and after the injection.

  Results: A stronger sickness response to LPS was significantly associated with a larger anterior insula gray matter volume, independently from increases in cytokine concentrations, age, sex and body mass index (R-2 = 65.6%). Similarly, a greater LPS-induced state anxiety response was related to a larger anterior insula gray matter volume, and also by a stronger increase in plasma TNF-alpha concentrations (R-2 = 40.4%).

  Discussion: Anterior insula morphology appears central in the sensitivity to develop symptoms of sickness and anxiety in response to inflammation, and could thus be one risk factor in inflammation-related psychopathologies. Because of the limited sample size, the current results need to be replicated.

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• Acute Systemic Experimental Inflammation Does Not Reduce Human Odor Identification Performance

  2021. Arnaud Tognetti (et al.). Chemical Senses 46

  Article

  Olfactory dysfunction is a common symptom of various diseases, but the underlying pathophysiology has not been fully understood. Evidence from both animal and human studies suggests that local inflammation of the olfactory epithelium is linked to olfactory dysfunction. However, whether systemic inflammation causes olfactory dysfunction is yet to be determined. In the present behavioral study, we set out to test whether acute systemic inflammation impairs olfactory identification performance by inducing a transient and controlled state of systemic inflammation using an experimental endotoxemia model. We treated young healthy participants (N = 20) with a relatively high dose (2.0 ng/kg) of lipopolysaccharide (LPS) and a placebo treatment in a double-blind within-subject design, and assessed participants' ability to identify odors using the MONEX-40, a reliable method for experimental assessment of odor identification ability in healthy and young individuals. Our results show that olfactory identification performance was not affected by the acute systemic inflammation triggered by the injection of LPS. Moreover, odor identification performance following the LPS injection was not associated with levels of circulating proinflammatory cytokines (interleukin-6, interleukin-8, and tumor necrosis factor-alpha). Because experimental LPS-induced systemic inflammation does not affect olfactory identification performance, our findings suggest that chronic, rather than transient, systemic inflammation is a more likely mechanism to explore in order to explain the olfactory deficits observed in inflammatory diseases.

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• Autistic Traits and Attention-Deficit Hyperactivity Disorder Symptoms Associated With Greater Pain Interference and Depression, and Reduced Health-Related Quality of Life in Children With Chronic Pain

  2021. Camilla Wiwe Lipsker (et al.). Frontiers in Neuroscience 15

  Article

  Previous research indicates elevated levels of clinically significant traits and symptoms of autism spectrum disorder and attention-deficit hyperactivity disorder (ADHD) in children with chronic pain, but associations with functioning and depression are yet unclear. The current study examined the relationships of autistic traits and ADHD symptoms with pain interference, depression, and health-related quality of life, as well as the mediating roles of insomnia and psychological inflexibility, in children with chronic pain (n = 146, 8-17 years, 102 girls) presenting at a tertiary pain clinic. Children completed measures of pain intensity, depression, pain interference, health-related quality of life, insomnia, and psychological inflexibility. Parents (n = 146, 111 mothers) completed measures to assess autistic traits and ADHD symptoms in their children. Children with clinically significant autistic traits and ADHD symptoms presented with significantly higher levels of depressive symptoms and pain interference, and significantly lower health-related quality of life, than did the other children. Autistic traits and ADHD symptoms contributed significantly to the prediction of pain interference and depressive symptoms, as well as health-related quality of life. Psychological inflexibility mediated the relationships between ADHD symptoms and autistic traits on the one hand and depression, pain interference, and health-related quality of life on the other, while insomnia mediated the relationships between ADHD symptoms and depression, pain interference, and health-related quality of life. All analyses were adjusted for demographics and pain intensity. Results suggest the utility of screening for neurodevelopmental disorders in children with chronic pain. Furthermore, the findings may indicate insomnia and skills related to psychological flexibility as potential treatment targets in interventions aiming at improving functioning and health-related quality of life in children with chronic pain and co-occurring symptoms of neurodevelopmental disorders.

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• Cortical thickness and resting-state cardiac function across the lifespan

  2021. Julian Koenig (et al.). Psychophysiology 58 (7)

  Article

  Understanding the association between autonomic nervous system [ANS] function and brain morphology across the lifespan provides important insights into neurovisceral mechanisms underlying health and disease. Resting-state ANS activity, indexed by measures of heart rate [HR] and its variability [HRV] has been associated with brain morphology, particularly cortical thickness [CT]. While findings have been mixed regarding the anatomical distribution and direction of the associations, these inconsistencies may be due to sex and age differences in HR/HRV and CT. Previous studies have been limited by small sample sizes, which impede the assessment of sex differences and aging effects on the association between ANS function and CT. To overcome these limitations, 20 groups worldwide contributed data collected under similar protocols of CT assessment and HR/HRV recording to be pooled in a mega-analysis (N = 1,218 (50.5% female), mean age 36.7 years (range: 12–87)). Findings suggest a decline in HRV as well as CT with increasing age. CT, particularly in the orbitofrontal cortex, explained additional variance in HRV, beyond the effects of aging. This pattern of results may suggest that the decline in HRV with increasing age is related to a decline in orbitofrontal CT. These effects were independent of sex and specific to HRV; with no significant association between CT and HR. Greater CT across the adult lifespan may be vital for the maintenance of healthy cardiac regulation via the ANS—or greater cardiac vagal activity as indirectly reflected in HRV may slow brain atrophy. Findings reveal an important association between CT and cardiac parasympathetic activity with implications for healthy aging and longevity that should be studied further in longitudinal research.

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• Human sickness detection is not dependent on cultural experience

  2021. Artin Arshamian (et al.). Proceedings of the Royal Society of London. Biological Sciences 288 (1954)

  Article

  Animals across phyla can detect early cues of infection in conspecifics, thereby reducing the risk of contamination. It is unknown, however, if humans can detect cues of sickness in people belonging to communities with whom they have limited or no experience. To test this, we presented Western faces photographed 2 h after the experimental induction of an acute immune response to one Western and five non-Western communities, including small-scale hunter-gatherer and large urban-dwelling communities. All communities could detect sick individuals. There were group differences in performance but Western participants, who observed faces from their own community, were not systematically better than all non-Western participants. At odds with the common belief that sickness detection of an out-group member should be biased to err on the side of caution, the majority of non-Western communities were unbiased. Our results show that subtle cues of a general immune response are recognized across cultures and may aid in detecting infectious threats.

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• Neuropsychiatric Symptoms in Pediatric Chronic Pain and Outcome of Acceptance and Commitment Therapy

  2021. Leonie J. T. Balter (et al.). Frontiers in Psychology 12

  Article

  Considerable heterogeneity among pediatric chronic pain patients may at least partially explain the variability seen in the response to behavioral therapies. The current study tested whether autistic traits and attention-deficit/hyperactivity disorder (ADHD) symptoms in a clinical sample of children and adolescents with chronic pain are associated with socioemotional and functional impairments and response to acceptance and commitment therapy (ACT) treatment, which has increased psychological flexibility as its core target for coping with pain and pain-related distress. Children and adolescents aged 8-18 years (N = 47) were recruited. Patients and their parents completed questionnaires pre- and post-ACT of 17 sessions. Correlational analyses and mixed-effects models were used to assess the role of autistic traits and ADHD symptoms in pretreatment functioning and ACT-treatment response. Outcome variables were degree to which pain interfered with daily activities (i.e., pain interference, sleep, and physical and school functioning), socioemotional functioning (i.e., depressive symptoms, emotional, and social functioning), psychological inflexibility, and pain intensity. Autistic traits and ADHD symptoms, pain frequency, and pain duration were measured at pretreatment only. Higher autistic traits were associated with greater pain interference, higher depression, and greater psychological inflexibility. Higher ADHD symptomatology was associated with greater pretreatment pain interference, lower emotional functioning, greater depression, and longer duration of pain. Across patients, all outcome variables, except for sleep disturbances and school functioning, significantly improved from pre- to post-ACT. Higher autistic traits were associated with greater pre- to post-ACT improvements in emotional functioning and sleep disturbance and non-significant improvements in pain interference. ADHD symptomatology was not associated with treatment outcome. The current results showed that neuropsychiatric symptoms in pediatric chronic pain patients are associated with lower functioning, particularly pain interfering with daily life and lower socioemotional functioning. The results suggest that not only pediatric chronic pain patients low in neuropsychiatric symptoms may benefit from ACT, but also those high in autism traits and ADHD symptoms. With the present results in mind, pediatric chronic pain patients higher in autistic traits may actually derive extra benefit from ACT. Future research could assess whether increased psychological flexibility, the core focus of ACT, enabled those higher in autism traits to cope relatively better with pain-related distress and thus to gain more from the treatment, as compared to those lower in autism traits. Moreover, to address specific effects of ACT, inclusion of an appropriate control group is key.

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• Objective and Subjective Sleep in Rheumatoid Arthritis and Severe Seasonal Allergy

  2021. Sandra Tamm (et al.). Nature and Science of Sleep 13, 775-789

  Article

  Introduction: Disturbed sleep in inflammatory disorders such as allergy and rheumatoid arthritis (RA) is common and may be directly or indirectly related to disease processes, but has not been well characterized in these patient groups, especially not with objective methods.

  Aim: The present study aimed to characterize objective and subjective sleep in patients with allergy or RA using sleep diaries, one-channel EEG and actigraphy. It also aimed to investigate if sleep measures were associated with central immune activation, assessed using translocator protein (TSPO) positron emission tomography, as well as cytokine markers of peripheral inflammation and disease-specific symptoms or general symptoms of sickness.

  Methods: In total, 18 patients with seasonal pollen allergy, 18 patients with RA and 26 healthy controls were included in the study. Allergy patients and matched controls were assessed twice, in and out of pollen season, and RA patients and controls were assessed once. Sleep was recorded for approximately 1 week at each occasion.

  Results: Patients with allergy had increased levels of slow-wave sleep during pollen season. In contrast, patients with RA had less SWS compared to healthy controls, while no differences were observed in sleep duration or subjective sleep quality. Across groups, neither proinflammatory cytokines, grey matter TSPO levels nor general sickness symptoms were associated with objective or subjective measures of sleep. Rhinitis, but not conjunctivitis, was correlated to worse subjective sleep and more slow wave sleep in allergy. Functional status, but not disease activity, predicted lower subjective sleep in RA.

  Conclusion: This study tentatively indicates that both patients with allergy and RA display sleep alterations but does not support inflammation as an independent predictor of the sleep disturbance across these patient groups.

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• Regulation of emotions during experimental endotoxemia

  2021. Lina S. Hansson (et al.). Brain, behavior, and immunity 93, 420-424

  Article

  Even though dysfunctional emotion regulation is prominent in depression and a link between depression and inflammation is well established, there is little knowledge about how inflammation affects the regulation of emotions. The aim of this pilot study was to explore the effect of experimentally induced inflammation on the cognitive reappraisal of emotions, and to assess domain specificity by comparing success in regulation of emotions towards two unpleasant stimuli classes (general negative stimuli and disgust stimuli). In a between-subject design, ten healthy participants were injected with an intravenous injection of lipopolysaccharide (2 ng/kg body weight) and eleven were injected with saline. Participants performed a cognitive reappraisal task, in which they had to down-regulate or up-regulate their emotions towards general negative stimuli and disgust stimuli, 5–6 h post-injection. Contrary to our hypotheses, participants injected with lipopolysaccharide reported greater success in down-regulating emotional responses towards unpleasant stimuli as compared to the saline group. In addition, both groups were poorer at down-regulating emotions towards disgust stimuli as compared to general negative stimuli. The current pilot study indicates that cognitive reappraisal of emotions is affected during experimental endotoxemia, and suggests that disgust stimuli might be difficult to reappraise.

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• The mediating role of insomnia severity in internet-based cognitive behavioral therapy for chronic stress

  2021. Elin Lindsäter (et al.). Behaviour Research and Therapy 136

  Article

  The aim of this study was to investigate insomnia symptom severity as a putative mediator of treatment response in therapist-guided internet-based cognitive behavioral therapy (ICBT) for chronic stress, using data from a randomized controlled trial. Participants (N = 100) were randomized to 12 weeks of ICBT or to a waitlist control condition (WLC). Insomnia severity was assessed weekly with the Insomnia Severity Index (ISI), as were the stress-related outcomes the Perceived Stress Scale (PSS) and the Shirom-Melamed Burnout Questionnaire (SMBQ). Latent growth models indicated that ICBT (vs. WLC) predicted a decrease in insomnia severity (alpha-path), and that growth in insomnia severity was predictive of growth in perceived stress and exhaustion (beta-paths). Most importantly, there were also significant indirect effects (alpha beta products) such that the beneficial effects of ICBT on perceived stress and exhaustion were mediated by a reduction in insomnia symptom severity (PSS: alpha beta =-0.44, 95% CI [-0.92,-0.14]; SMBQ: alpha beta =-0.08, 95% CI [-0.15, 0.04]). Explorative analysis of moderated mediation showed that more severe insomnia symptoms at baseline were associated with larger mediated effects. We conclude that reducing insomnia severity could be of importance for achieving successful treatment outcomes in ICBT for chronic stress.

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• Vulnerability in Executive Functions to Sleep Deprivation Is Predicted by Subclinical Attention-Deficit/Hyperactivity Disorder Symptoms

  2021. Orestis Floros (et al.). Biological Psychiatry 6 (3), 290-298

  Article

  Background: Sleep loss results in state instability of cognitive functioning. It is not known whether this effect is more expressed when there is an increased cognitive demand. Moreover, while vulnerability to sleep loss varies substantially among individuals, it is not known why some people are more affected than others. We hypothesized that top-down regulation was specifically affected by sleep loss and that subclinical inattention and emotional instability traits, related to attention-deficit/hyperactivity disorder symptoms, predict this vulnerability in executive function and emotion regulation, respectively.

  Methods: Healthy subjects (ages 17–45 years) rated trait inattention and emotional instability before being randomized to either a night of normal sleep (n = 86) or total sleep deprivation (n = 87). Thereafter, they performed a neutral and emotional computerized Stroop task, involving words and faces. Performance was characterized primarily by cognitive conflict reaction time and reaction time variability (RTV), mirroring conflict cost in top-down regulation.

  Results: Sleep loss led to increased cognitive conflict RTV. Moreover, a higher level of inattention predicted increased cognitive conflict RTV in the neutral Stroop task after sleep deprivation (r = .30, p = .0055) but not after normal sleep (r = .055, p = .65; interaction effect β = 6.19, p = .065). This association remained after controlling for cognitive conflict reaction time and emotional instability, suggesting domain specificity. Correspondingly, emotional instability predicted cognitive conflict RTV for the emotional Stroop task only after sleep deprivation, although this effect was nonsignificant after correcting for multiple comparisons.

  Conclusions: Our findings suggest that sleep deprivation affects cognitive conflict variability and that less stable performance in executive functioning may surface after sleep loss in vulnerable individuals characterized by subclinical symptoms of inattention.

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• Work ability and psychological distress in a working population

  2021. Clara Onell (et al.). Scandinavian Journal of Public Health

  Article

  Aims: Psychological distress is a global public health concern with individual and societal implications causing work-related disability and loss of productivity. It is less known how much work ability contributes to the development of psychological distress. This study aimed to assess the association between self-perceived physical and mental work ability in relation to job demands, and the incidence of psychological distress in a Swedish working population.

  Methods: Data were obtained from three subsamples of the Stockholm Public Health Cohort with baseline in 2010 and follow-up in 2014, based on a working population in Stockholm County aged 18–60 years, with no or mild psychological distress at baseline (n=29,882). Self-perceived physical and mental work ability in relation to job demands were assessed at baseline with a subscale from the Work Ability Index. Study participants scoring 4 or more on the General Health Questionnaire 12 at follow-up were classified as having developed psychological distress during the study period. Poisson log linear regression was used to calculate crude and adjusted rate ratios with 95% confidence intervals.

  Results: At follow-up, 2543 participants (12%) had developed psychological distress. Reporting poor physical and/or poor mental work ability in relation to job demands at baseline was associated with an almost doubled rate ratio of psychological distress at follow-up, compared to reporting good work ability (rate ratio 1.8; 95% confidence interval 1.6–2.0).

  Conclusions: Poor work ability is associated with a higher incidence of future psychological distress compared to good work ability.

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Show all publications by Mats Lekander at Stockholm University