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.

The International Congress on Autoimmune Pre-Disease was organized by the German Research Foundation–founded Research Training Group “Autoimmune Pre-Disease” and took place at the University of Lübeck, Germany, on September 16–17, 2024. The event featured various talks and posters from young researchers and international experts and emphasized early interventions and prevention in autoimmune diseases with a focus on systemic rheumatic diseases, pemphigus, and pemphigoid diseases.

While altered motivation is central in sickness behavior, previous research has mainly focused on motivation for rewards, rather than motivational changes in a broader perspective. In a larger study following a randomized within-subject placebo-controlled crossover design, we investigated the effects of systemic inflammatory activation on self-rated motivation in 21 healthy participants, using an intravenous injection of 2.0 ng/kg body weight lipopolysaccharide (LPS) compared to an intravenous injection of saline (placebo). Self-rated motivation was measured before, 3 h, and 7.5 h post-injection using the Motivation Scale of Sickness (MOSSick), a newly developed tool designed to assess motivational changes during sickness. It contains 26 items covering motivational drives related to hunger, thirst, and food preferences; resting, physical, and social activities; care seeking; and utilization of resources (i.e., willingness to ‘pay’ and ‘walk’) to be able to rest or to be healthy at once. At the peak of the sickness response (3 h post-LPS injection), there was an increased motivation to seek care, rest, and sleep, as compared to placebo, while motivation to partake in physical and social activities decreased. Several of these effects remained at 7.5 h post-injection. When in the LPS condition, participants were also willing to pay more money to rest and to be healthy compared to when in the placebo condition. Hunger increased over time in both conditions, but less after LPS administration. During the peak of the sickness response, higher sickness ratings were weakly associated with lower motivation for social activities and higher motivation for resting and sleeping. No further association was found between motivational drives and sickness ratings or other sickness measures, i.e. concentrations of cytokines and tympanic temperature, although sample size was limited for these analyses. These findings illustrate that motivational changes during acute sickness are not restricted to a general decrease in motivation. Instead, sick individuals are more motivated to take part in behaviors that enable energy preservation, care, and recovery, compared to when healthy.

Motivations to avoid infectious disease seem to influence prejudice toward some groups, including groups not explicitly associated with infectious disease. The standard explanation for this phenomenon is based on signal detection theory and proposes that some prejudices partially arise from pathogen detection mechanisms that are biased toward making false alarms (false positives) in order to minimize misses (false negatives). Therefore, pathogen detection mechanisms arguably categorize a broad array of atypical features as indicative of infection, which gives rise to negative affect toward people with atypical features. We tested a key hypothesis derived from this explanation: specific appearance-based prejudices are associated with tendencies to make false alarms when estimating the presence of infectious disease. While this hypothesis is implicit in much work on the behavioral immune system and prejudice, direct tests of it are lacking and existing relevant work contains important limitations. To test the hypothesis, we conducted a cross-sectional study using a large U.S. sample (N = 1450). Using signal detection theory methods, we assessed tendencies to make false alarms when identifying infection threats. We further assessed prejudice toward multiple relevant social groups/categories. Results showed weak evidence for the key hypothesis: for only one of four tested target groups were tendencies to make false alarms in sickness detection significantly associated with prejudice. However, this relation was not significant when controlling for a potential confound. These results cast doubt on the notion that individual differences in appearance-based prejudices arise from individual differences in tendencies to make false alarms in assessing pathogen threats.

Social withdrawal is a well-established part of sickness behavior, but in some contexts sick animals might gain from keeping close instead of keeping away. For instance, sick individuals are more willing to be near known individuals who can provide care and safety (close others) compared to when healthy. Yet, interactions with some strangers might also be beneficial (i.e., healthcare professionals), but it is not known how sickness interplay with social behavior towards such individuals. Here, we assessed if sickness affects perception of caregivers, and developed a new task, the Caregiver Perception Task (CgPT). Twenty-six participants performed the CgPT, once after an injection of lipopolysaccharide (LPS, 0.8 ng/kg body weight, n = 24), and once after an injection of saline (n = 25), one hour and forty-five minutes post-injection. During the task, participants watched short video clips of three types of caregivers: a healthcare professional taking care of a sick individual, a healthcare professional not taking care of a sick individual, and a non-healthcare professional taking care of their sick adult child or partner. After each video clip, the likability, trustworthiness, professionalism, and willingness to interact with and receive care from the caregiver were rated on visual analogue scales. Results showed that participants injected with saline rated healthcare professionals who did not take care of a sick individual less positively on all aspects compared to healthcare professionals who took care of a sick individual. Moreover, compared to saline, LPS increased the participants’ willingness to receive care from healthcare professionals and non-healthcare professionals providing care, but not from healthcare professionals not providing care. Thus, our results indicate that sick individuals may approach unknown individuals with potential to provide care and support.

The Sickness Questionnaire (SicknessQ) is a questionnaire developed to assess symptoms of sickness behavior, including somatic, behavioral, and affective dimensions. To promote cross-cultural assessments of sickness behavior, we aim to expand the use of this questionnaire to other populations and languages. The aim of the present study was to evaluate the French translation of SicknessQ in a French-speaking general population during the COVID-19 pandemic. One hundred and thirty-nine individuals completed the SicknessQ online, along with the construct criteria measures of self-rated health, state anxiety (STAI-S), and depressive symptoms (PHQ-9). The principal component analyses revealed two components: the first component included seven items concerning mood, motivation and experiences of fatigue and pain; the second component included three items concerning somatic sickness symptoms. Higher scores on the total scale and the two component subscales were associated with poorer self-rated health and higher STAI-S and PHQ-9 scores. Since the associations with construct criteria variables were relatively similar between the single- and the two-dimensional solutions, both the total scale and the subscales of the two components of the French SicknessQ can be used in future studies to measure sickness behavior in French-speaking populations.

A workshop titled “Beyond the Symptom: The Biology of Fatigue” was held virtually September 27–28, 2021. It was jointly organized by the Sleep Research Society and the Neurobiology of Fatigue Working Group of the NIH Blueprint Neuroscience Research Program. For access to the presentations and video recordings, see: https://neuroscienceblueprint.nih.gov/about/event/beyond-symptom-biology-fatigue.

The goals of this workshop were to bring together clinicians and scientists who use a variety of research approaches to understand fatigue in multiple conditions and to identify key gaps in our understanding of the biology of fatigue. This workshop summary distills key issues discussed in this workshop and provides a list of promising directions for future research on this topic. We do not attempt to provide a comprehensive review of the state of our understanding of fatigue, nor to provide a comprehensive reprise of the many excellent presentations. Rather, our goal is to highlight key advances and to focus on questions and future approaches to answering them.

Interoception refers to the sensing, interpreting, and integration of signals coming from the body (i.e., interoceptive signals) by the nervous system (Allen, 2020, Khalsa et al., 2018). Alterations in the processing of interoceptive signals is believed to significantly play a role in the development of mental health conditions (Barrett, 2017, Khalsa et al., 2018), and the methodology for human interoception research is expanding (Garfinkel et al., 2022). Investigations in the field have mostly been restricted to the domain of cardiovascular signals, as well as to the respiratory and gastrointestinal axes (Benson et al., 2012, Garfinkel et al., 2016, Khalsa and Lapidus, 2016). The reason is most likely that humans' appraisal of the status of these signals are commonly explicit and frequently occurring, and due to the fact that the assessment of perceptual alterations in interoceptive awareness (i.e., interoceptive attention, accuracy, intensity, sensibility, and insight) of these signals is convenient. There is less consensus regarding whether other types of bodily signals, such as the status of other organs or various hormonal levels, are reachable in an explicit manner. The study by Dimitroff et al. (2023) suggests, for the first time, that we humans can perhaps explicitly estimate our actual immune response.

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.