Disruptions in sleep and circadian rhythms have been consistently linked to higher mortality rates in the general population. Among cancer patients, these disruptions are not only prevalent but may significantly influence prognosis. Despite this, sleep and circadian trajectories remain unexplored in the context of cancer, particularly related to prognostic outcomes in modern therapies such as immune checkpoint inhibitors (ICIs), which are rapidly transforming oncological care. In this pioneering report, we examined how trajectories of sleep and circadian rhythms relate to prognostic outcomes in patients with non–small cell lung cancer (NSCLC), offering novel insights into their potential role as modifiable biomarkers of clinical outcomes. Forty-nine treatment-naïve NSCLC patients were enrolled in this prospective longitudinal study. Continuous 24-h recordings of circadian function (Circadian Function Index [CFI]) were collected over the first 5 months of treatment, alongside weekly assessments of insomnia severity (Insomnia Severity Index [ISI]) and estimations of total sleep time (TST) derived from sleep diaries every 3 weeks. Follow-up data, time to treatment discontinuation, disease progression, and cancer-related death were obtained from medical records. We estimated hazard ratios (HRs) for these outcomes based on ISI, TST, and CFI, analyzed as continuous variables and median-split. Cox regression analyses indicated that patients with trajectories portraying circadian robustness below the median had a higher risk of earlier progression (HR = 3.75, 95% confidence interval [CI] = [1.475-9.536], p = 0.005) and death (HR = 3.07, 95% CI = [1.128-8.360], p = 0.028). No significant associations were found between insomnia severity, TST, and the prognostic outcomes. Patients with more pronounced declines in circadian robustness demonstrated significantly elevated risks of disease progression and mortality. As the circadian rhythm is modifiable, these findings, if replicated, underscore the need for interventional studies aimed at stabilizing circadian rhythms to further explore potential improvements in patient outcomes and efficacy of cancer therapies.

Objectives: People in Sweden have internationally good health, work environment and quality of life, a picture that has lately been questioned because of the sharp increase in stress-related diagnoses, especially among young women. This study aims to better understand how stress and psychosocial work stressors vary across age and birth cohorts using data collected between 2008 and 2018. Methods: Using hierarchical age-period-cohort-growth curve models and data from the Swedish Longitudinal Occupational Survey of Health, we estimated the age trajectories of job demands, job control, perceived long-lasting stress, sustained emotional stress and self-rated health by birth cohort. Separate analyses by sex and occupational status were also conducted. Results: Job demands, perceived long-lasting stress and sustained emotional stress decreased with age, while self-rated health deteriorated. Statistically significant cohort and age × cohort interactions suggest that more recent birth cohorts have both a) higher job demands, lower job control, more sustained emotional stress and worse self-rated health, and b) a less favourable development with age for all outcomes. However, these cohort differences are primarily driven by younger cohorts, and they are less pronounced or inconsistent among older cohorts. Occupational status and gender seem to modify some of these developments. Conclusions: This study provides some support for inter-cohort changes in the work environment and health, predominantly among younger cohorts. More recent cohorts generally report poorer health and work environment along with less favourable development with age. Nevertheless, these patterns are not consistent across all age group comparisons and robust cohort comparisons are primarily possible among adjacent cohorts. It is, however, unlikely that these changes can be attributed solely to a general deterioration in working life affecting all workers equally, as the phenomenon appears largely confined to younger workers. Future studies should explore how the combined demands from several spheres of life may better explain these age and cohort differences.

Background: Inflammation is increasingly considered a vulnerability factor for deficits in reward motivation. It remains unclear if such motivational changes differ between acute and chronic low-grade inflammation. Given obesity’s link to chronic low-grade inflammation, the present study a priori tested the effects of obesity and low-grade inflammation (elevated CRP concentrations), as well as acute inflammation (experimental immune challenge using lipopolysaccharide), on motivation for a monetary reward. Moreover, the wear-and-tear induced by chronic inflammation could amplify motivational changes induced by immune challenge. Thus, we also tested the a priori hypotheses that acute inflammation is associated with more strongly altered reward motivation for individuals with higher low-grade inflammation, and for obese than normal-weight individuals.

Methods: Obese (n = 14) and normal-weight (n = 21) young adults, all without current or past history of medical or psychiatric conditions, were intravenously injected with a bacterial endotoxin (lipopolysaccharide, LPS [0.8 ng/kg body weight]) to trigger an acute inflammatory response, and placebo (saline) in a counterbalanced, randomized, crossover design. The Effort Expenditure for Reward Task (EEfRT) was administered 2 h following each injection to assess reward motivation. Blood was sampled pre- and post-injection to quantify concentrations of inflammatory proteins (interleukin [IL]-6 and C-reactive protein [CRP]).

Results: Obesity and higher low-grade inflammation (baseline CRP) were associated with overall reduced motivation to expend effort for reward in the placebo condition. Interactions with reward magnitude were observed, so that this effect occurred at smaller reward values, but not when reward values increased. However, these interaction effects were not significant in a posteriori sensitivity analyses. LPS-induced inflammatory responses (IL-6 concentrations during EEfRT) were associated with a weaker influence of reward magnitude on increasing effort. Unexpectedly, we did not detect the amplification effect of obesity and its associated low-grade inflammation on the ability of lipopolysaccharide to modulate reward motivation.

Conclusions: Lipopolysaccharide-induced and low-grade inflammation may alter how effort is allocated towards reward: low-grade inflammation reduced the willingness to expend effort, while acute inflammation dampened reward sensitivity. This study offers a nuanced understanding of inflammatory processes underlying alterations in reward motivation.

Sleep loss and low-grade inflammation are common stressors that affect behaviour and recovery needs. To examine their separate and combined effects on motivation for everyday behaviours, we developed a two-hit experimental model. Participants (N = 56, 31 women) completed three experimental visits: sleep saturation (two nights, 9 h in bed/night); sleep-restriction (two nights, 4 h in bed/night); and an immune challenge (~24 h post COVID-19 vaccination) combined with either sleep saturation (n = 26) or restriction (n = 30). Motivation for everyday behaviours and sleepiness were rated, and blood samples were collected. Both sleep restriction and vaccination increased motivation for sleep-related behaviours and reduced motivation for physical and social activity, with sleep restriction having broader effects. These changes were associated with inflammation and sleepiness. Vaccination increased thirst, while sleep restriction reduced it, but neither affected hunger or food preferences. Sleep restriction amplified the inflammatory response to vaccination. For motivation, the stressors combined caused larger changes than either alone for some outcomes, without amplifying one another. These findings support that different stressors reallocate motivation towards rest and sleep-supporting behaviours over physical and social activity, likely to drive behaviours that support homeostasis after allostatic challenges. As these stressors often co-occur, this adaptive response can meaningfully shape daily functioning. Future work may determine when this functional response becomes maladaptive.

Background: The use of artificial intelligence for psychological advice shows promise for enhancing accessibility and reducing costs, but it remains unclear whether AI-generated advice can match the quality and empathy of experts.

Method: In a blinded, comparative cross-sectional design, licensed psychologists and psychotherapists assessed the quality, empathy, and authorship of psychological advice, which was either AI-generated or authored by experts.

Results: AI-generated responses were rated significantly more favorable for emotional (OR = 1.79, 95 % CI [1.1, 2.93], p = .02) and motivational empathy (OR = 1.84, 95 % CI [1.12, 3.04], p = .02). Ratings for scientific quality (p = .10) and cognitive empathy (p = .08) were comparable to expert advice. Participants could not distinguish between AI- and expert-authored advice (p = .27), but perceived expert authorship was associated with more favorable ratings across these measures (ORs for perceived AI vs. perceived expert ranging from 0.03 to 0.15, all p < .001). For overall preference, AI-authored advice was favored when assessed blindly based on its actual source (β = 6.96, p = .002). Nevertheless, advice perceived as expert-authored was also strongly preferred (β = 6.26, p = .001), with 93.55 % of participants preferring the advice they believed came from an expert, irrespective of its true origin.

Conclusions: AI demonstrates potential to match expert performance in asynchronous written psychological advice, but biases favoring perceived expert authorship may hinder its broader acceptance. Mitigating these biases and evaluating AI's trustworthiness and empathy are important next steps for safe and effective integration of AI in clinical practice.

Exhaustion disorder (ED) was introduced to the Swedish version of the International Classification of Diseases, 10th edition (ICD-10) 2005. Primarily characterized by general fatigue and cognitive deficits, ED has become one of the most common mental health diagnoses in Sweden. Little is still known regarding the discriminative validity of the ED diagnosis and how it relates to other diagnostic constructs. The study aimed to investigate the discriminative validity of ED compared with two similar diagnoses, major depressive disorder (MDD) and adjustment disorder (AD). Using data from a sample of patients with a principal diagnosis of either ED (n = 352), MDD (n = 99), or AD (n = 302), we compared demographic and clinical variables and scores on self-report symptom scales. Results showed that ED patients were of a higher age and had a higher frequency of sickness absence than MDD and AD patients. There was a substantial overlap of symptoms between ED and MDD, only differing on two of nine self-report symptom scales, with ED patients rating lower work ability d = −0.37 and alcohol consumption d = −0.57. Compared with AD patients, ED patients reported more severe symptoms in every symptom domain. Given the prevalent use of ED diagnosis, its diagnostic validity and clinical usefulness merit further attention.

A behavioral defense against disease involves detecting sickness cues in others and responding adaptively, such as by avoiding social interactions. While studies have shown that humans can discriminate sickness cues above chance in faces after sickness induction, whether this discrimination affects approach-avoidance behaviors remains uncertain. Here, we investigated how facial sickness cues influence judgments of trustworthiness, serving as a proxy measure for social avoidance. In a prior study, facial photographs were taken of 21 individuals when sick (two hours after an endotoxin injection causing a transient systemic inflammation) and healthy (following placebo injection). In the current study, participants in two separate experiments viewed these paired facial photographs and were asked, in a two-alternative forced-choice paradigm, to identify which face appeared sick (n = 94) or more trustworthy (n = 82). Participants discriminated sick faces significantly above chance (73.1 %), with females (76.0 %) performing significantly better than males (69.3 %). Additionally, sick faces were perceived as significantly less trustworthy, being selected in only 34.9 % of trials. Notably, the higher the sickness discrimination accuracy for a particular face, the less likely that face was to be judged as trustworthy. Moreover, females (30.5 %) were significantly less likely than males (39.5 %) to judge sick faces as the more trustworthy looking. Individual differences in participants’ disease vulnerability, disgust sensitivity, and frequency of sickness, as well as facial stimulus participants’ inflammatory response intensity measured via interleukin-6 blood concentrations, body temperature, and sickness symptoms, did not predict sickness discrimination accuracy or trustworthiness judgments. Together, these findings suggest that visual sickness cues negatively affect trustworthiness judgments, potentially reflecting social avoidant behaviors towards individuals who appear sick. While judgments of facial trustworthiness may be considered a social inference about whether an individual is safe to approach, future research should also include manifest measures of approach-avoidance in response to sickness cues.

Sick humans and other animals often withdraw from social interactions. It has been suggested that social withdrawal might enable avoidance of contagious individuals, but experimental evidence is lacking on how the state of sickness may affect perception of sick others. Here, we investigated if individuals were more likely to rate others as sick, while being sick themselves, compared to when healthy. Furthermore, we assessed whether the intensity of the fever response and sickness behavior would predict changes in sickness detection. Thirty-four participants were experimentally made sick using an intravenous injection of the bacterial endotoxin lipopolysaccharide (LPS condition; dose of 1.0 ng/kg body weight) and completed a sickness detection task during the peak of the inflammatory and sickness response. Participants performed the same task when they were healthy (control condition, n = 32), in a randomized order before or after the main study day. In the sickness detection task, participants watched photos of individuals’ faces as well as video recordings of the same individuals walking, and rated the individual on each stimulus as sick or healthy. The photos and video recordings were obtained from twenty-two individuals who had participated in a previous study, and had been made sick with an intravenous injection of lipopolysaccharide (2.0 ng/kg body weight) on one occasion, and remained healthy after an intravenous injection of a placebo (0.9 % NaCl) on another occasion. Participants could detect sick individuals based on photos and walking patterns above chance level during both the LPS and the control condition. There was no significant difference in how often participants identified sick faces and sick walkers in the LPS condition – when they were sick themselves – compared to in the control condition. However, healthy walkers (but not healthy faces) were more often rated as sick by participants in the LPS condition compared to the control condition. Neither the fever response nor the intensity of sickness behavior predicted changes in sickness detection. The results do not indicate more accurate sickness detection in others during own sickness. Nevertheless, the data from walking patterns indicate that sick individuals may be more prone to categorize healthy individuals as sick. If replicated, this could in speculation be related to a need to reduce the risk of becoming infected while already fighting a pathogen.

Introduction: Stress-related disorders such as adjustment disorder (AD) and exhaustion disorder (ED) are associated with substantial suffering and high societal costs. Cognitive behavioral therapy (CBT) is a promising treatment for symptom reduction but has not been rigorously compared with other active treatments. This study aimed to investigate the efficacy of CBT compared to an active control treatment (General Health Promotion; GHP) for individuals diagnosed with AD or ED. Methods: A total of 300 adults diagnosed with AD or ED were randomly assigned to a 12-week CBT (n = 151) or GHP (n = 149), both delivered as therapist-supported online treatments. The primary outcome was post-treatment scores on the 10-item Perceived Stress Scale. Secondary outcomes included several mental health symptom domains and functional impairment. All outcomes were assessed at baseline, post-treatment, and at 1-year follow-up. The trial was pre-registered on Clinicaltrials.gov (NCT04797273). Results: The CBT intervention was not superior to GHP in reducing symptoms of perceived stress and secondary symptoms. Both treatments generated large within-group effect sizes pre- to post-treatment (Cohen's d = 1.19 and 1.06, respectively) and results were maintained to the 1-year follow-up. The diagnostic group moderated the treatment effect pre- to post-treatment and indicated that CBT was superior to GHP for individuals diagnosed with AD but not for those diagnosed with ED. Conclusions: Common factors likely play an important role in symptom reduction for individuals with stress-related disorders. A refined understanding of the conceptualization of stress-related disorders and which specific mechanisms to target in respective patient groups is needed to improve treatment outcomes.

Background: Patients with advanced non-small cell lung cancer (NSCLC) face poor prognosis. However, new therapies like immune checkpoint inhibitors (ICIs) have improved survival. Nevertheless, ICIs act through immune activation – a proposed underlying mechanism of frequently reported symptoms such as sleep and circadian disturbances. The objective of this study was to longitudinally investigate sleep and circadian rest-activity rhythms and associations with psychological symptoms in NSCLC during ICI treatment. Methods: Newly diagnosed NSCLC patients were included in this prospective study, assessing insomnia severity, total sleep time, circadian rest-activity rhythms, and psychological symptoms (fatigue, depression, and stress) during the first five months of ICI treatment, using validated questionnaires, sleep diaries and actigraphy. Results: Forty-nine patients were included. Prior to treatment, patients slept on average 5.8 hours/night and 49 % reported clinical levels of insomnia. Spontaneous improvements in insomnia severity and total sleep time were observed, along with marginal but non-significant improvements in circadian rest-activity rhythm robustness. Insomnia severity was significantly associated with higher levels of fatigue (p = .004), depression (p = .007), and perceived stress (p = .033). Moreover, lower circadian rest-activity robustness was associated with more fatigue (p = .021). At baseline, mean levels of fatigue, depression, and perceived stress were below clinical levels and declined further over time. Conclusion: Sleep disturbances, circadian disruption, and psychological symptom burden in NSCLC patients were greatest prior to and shortly after initiation of ICI treatment, with gradual improvement over the first five months. However, inter-individual differences in sleep and circadian disturbances were evident and linked to psychological symptoms.