A selection from Stockholm University publication database

• 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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• Working memory load impairs transfer learning in human adults

  2023. Leonie J. T. Balter, Jane E. Raymond. Psychological Research 87, 2138-2145

  Article

  Transfer of learning refers to successful application of previously acquired knowledge or skills to novel settings. Although working memory (WM) is thought to play a role in transfer learning, direct evidence of the effect of limitations in WM on transfer learning is lacking. To investigate, we used an acquired equivalence paradigm that included tests of association and transfer learning. The effects of imposing an acute WM limitation on young adults was tested (within-subjects design: N = 27 adults; M_age = 24 years) by conducting learning transfer tests concurrent with a secondary task that required carrying a spatial WM load when performing the learned/transfer trial (Load condition) to acutely limit WM resources or no WM load (No-Load condition; WM was unloaded prior to performing the learned/transfer trial). Analyses showed that although success on the transfer trials was high in the No-Load condition, performance dropped to chance in the Load condition. Performance on tests of learned associations remained high in both conditions. These results indicate that transfer of learning depends on access to WM resources and suggest that even healthy young individuals may be affected in their ability to cross-utilize knowledge when cognitive resources become scarce, such as when engaging in two tasks simultaneously (e.g., using satellite navigation while driving).

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• Intelligence predicts better cognitive performance after normal sleep but larger vulnerability to sleep deprivation

  2022. Leonie J. T. Balter (et al.). Journal of Sleep Research

  Article

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• Experimental Sleep Deprivation Results in Diminished Perceptual Stability Independently of Psychosis Proneness

  2022. Leonie J. T. Balter (et al.). Brain Sciences 12 (10)

  Article

  Psychotic disorders as well as psychosis proneness in the general population have been associated with perceptual instability, suggesting weakened predictive processing. Sleep disturbances play a prominent role in psychosis and schizophrenia, but it is unclear whether perceptual stability diminishes with sleep deprivation, and whether the effects of sleep deprivation differ as a function of psychosis proneness. In the current study, we aimed to clarify this matter. In this preregistered study, 146 participants successfully completed an intermittent version of the random dot kinematogram (RDK) task and the 21-item Peters Delusion Inventory (PDI-21) to assess perceptual stability and psychosis proneness, respectively. Participants were randomized to sleep either as normal (8 to 9 h in bed) (n = 72; Mage = 24.7, SD = 6.2, 41 women) or to stay awake through the night (n = 74; Mage = 24.8, SD = 5.1, 44 women). Sleep deprivation resulted in diminished perceptual stability, as well as in decreases in perceptual stability over the course of the task. However, we did not observe any association between perceptual stability and PDI-21 scores, nor a tendency for individuals with higher PDI-21 scores to be more vulnerable to sleep-deprivation-induced decreases in perceptual stability. The present study suggests a compromised predictive processing system in the brain after sleep deprivation, but variation in psychosis trait is not related to greater vulnerability to sleep deprivation in our dataset. Further studies in risk groups and patients with psychosis are needed to evaluate whether sleep loss plays a role in the occurrence of objectively measured perceptual-related clinical symptoms.

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• Sickness and sleep health predict frustration and affective responses to a frustrating trigger

  2021. Leonie J. T. Balter, Tina Sundelin, John Axelsson. Scientific Reports 11 (1)

  Article

  Fluctuations in health and sleep are common, but we know surprisingly little about how these daily life stressors affect one's level of frustration and sensitivity to becoming frustrated. In this pre-registered study, 517 participants (M_age = 30.4, SD = 10.4) reported their current sickness symptoms, health status, sleepiness, and sleep duration and quality the previous night. They also rated their general frustration and mood before and after a mild frustration-eliciting task. In the task, participants were instructed to copy geometric shapes onto a piece of paper, without lifting the pen from the paper. Participants were given three minutes to copy the eight shapes, but in order to induce frustration half of them were unsolvable. The study was subsequently repeated in an independent sample (N = 113). Frustration increased in response to the task; however, those with the worst sickness symptoms or sleep health reduced or did not change their frustration levels. Instead, across both studies, frustration was already high at baseline for these individuals. These findings indicate that being sick or having poor sleep is related to high general frustration, but resilience to further frustration due to mild frustrating situations.

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• Poor sleep quality is associated with worse self-rated health in long sleep duration but not short sleep duration

  2021. Anna Andreasson (et al.). Sleep Medicine 88, 262-266

  Article

  Unhealthy sleep duration, either short or long, is associated with worse health and central subjective dimensions of sleep and health such as fatigue. It has been argued that the link between sleep duration and health may depend on the quality of the slept hours, and on its functional impact (ie, fatigue). The present study therefore assessed whether the relationship between last night's sleep duration and general self-rated health (SRH) differs as a function of sleep quality, and secondly, whether current fatigue and sleep quality are factors linking sleep duration and SRH. The present cross-sectional dataset involved 1304 individuals (57% female, M age = 28.8, range 18-79). Participants completed surveys for general SRH, previous night's sleep duration and sleep quality, and current fatigue. Results showed the expected inverted U-shaped (ie, quadratic) relation between last night's sleep duration and SRH and a linear relation between last night's sleep quality and SRH. However, long sleep duration was only associated with poorer SRH in individuals who also reported poor sleep quality. Further, the quadratic relationship between sleep duration and SRH was partially mediated by fatigue and sleep quality. The results of this multi-study analysis suggest that SRH is particularly poor in those who slept both long and with poor quality the night before, while good sleep quality may protect those with a long sleep duration from poor SRH. Thus, last night's long sleep does not seem to be associated with poor subjective health unless it is coupled with poor sleep quality. Furthermore, fatigue and sleep quality are potential pathways linking short and long sleep duration with SRH. Different dimensions of sleep interact in their association with health, and future research will benefit from an integrative approach. 

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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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• 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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• Age, BMI, and inflammation

  2021. Leonie J. T. Balter (et al.). Physiology and Behavior 232

  Article

  Experimental studies show that inflammation impairs the ability to interpret the mental state of another person, denoted theory of mind (ToM). The current study attempted a conceptual replication in states associated with elevated low-grade inflammation, i.e., high body weight and advanced age. Ninety young (M = 26.3 years, SD = 4.1) or older (M = 70.7 years, SD = 4.0) participants with either a normal body mass index (BMI) (M = 22.4, SD = 2.2) or high BMI (M = 33.1, SD = 3.8) completed the Reading the Mind in the Eyes Test (RMET) to assess emotion recognition. Plasma interleukin-6 (IL-6) level was measured to index low-grade inflammation. As anticipated, elevated IL-6 levels were found with higher BMI, although not with increased age. IL-6 was associated with poorer task performance, independent of potential demographic and health confounders (e.g., sex, education, smoking status, alcohol intake, presence of medical conditions, and medication intake). Analyses also revealed an interaction whereby young individuals with a high BMI showed worse RMET performance compared to their normal BMI counterparts, whereas the opposite pattern was found in older individuals. The present observational study replicated experimental results showing that elevated low-grade inflammation is correlated with a lower ability to infer the mental states of others. These findings suggest that also naturalistic conditions of (protracted) low-grade inflammation may alter emotion recognition.

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Show all publications by Leonie Balter at Stockholm University