An ERP Study of Face Processing in Schizophrenia, Bipolar Disorder, and Socially Isolated Individuals from the Community.

People with schizophrenia (SCZ) and bipolar disorder (BD) have impairments in processing social information, including faces. The neural correlates of face processing are widely studied with the N170 ERP component. However, it is unclear whether N170 deficits reflect neural abnormalities associated with these clinical conditions or differences in social environments. The goal of this study was to determine whether N170 deficits would still be present in SCZ and BD when compared with socially isolated community members. Participants included 66 people with SCZ, 37 with BD, and 125 community members (76 "Community-Isolated"; 49 "Community-Connected"). Electroencephalography was recorded during a face processing task in which participants identified the gender of a face, the emotion of a face (angry, happy, neutral), or the number of stories in a building. We examined group differences in the N170 face effect (greater amplitudes for faces vs buildings) and the N170 emotion effect (greater amplitudes for emotional vs neutral expressions). Groups significantly differed in levels of social isolation (Community-Isolated > SCZ > BD = Community-Connected). SCZ participants had significantly reduced N170 amplitudes to faces compared with both community groups, which did not differ from each other. The BD group was intermediate and did not differ from any group. There were no significant group differences in the processing of specific emotional facial expressions. The N170 is abnormal in SCZ even when compared to socially isolated community members. Hence, the N170 seems to reflect a social processing impairment in SCZ that is separate from level of social isolation.

Social cognition and social motivation in schizophrenia and bipolar disorder: are impairments linked to the disorder or to being socially isolated?

BACKGROUND: People with schizophrenia on average are more socially isolated, lonelier, have more social cognitive impairment, and are less socially motivated than healthy individuals. People with bipolar disorder also have social isolation, though typically less than that seen in schizophrenia. We aimed to disentangle whether the social cognitive and social motivation impairments observed in schizophrenia are a specific feature of the clinical condition v. social isolation generally. METHODS: We compared four groups (clinically stable patients with schizophrenia or bipolar disorder, individuals drawn from the community with self-described social isolation, and a socially connected community control group) on loneliness, social cognition, and approach and avoidance social motivation. RESULTS: Individuals with schizophrenia (n = 72) showed intermediate levels of social isolation, loneliness, and social approach motivation between the isolated (n = 96) and connected control (n = 55) groups. However, they showed significant deficits in social cognition compared to both community groups. Individuals with bipolar disorder (n = 48) were intermediate between isolated and control groups for loneliness and social approach. They did not show deficits on social cognition tasks. Both clinical groups had higher social avoidance than both community groups. CONCLUSIONS: The results suggest that social cognitive deficits in schizophrenia, and high social avoidance motivation in both schizophrenia and bipolar disorder, are distinct features of the clinical conditions and not byproducts of social isolation. In contrast, differences between clinical and control groups on levels of loneliness and social approach motivation were congruent with the groups' degree of social isolation.

Inaugural editorial.

Eisenberger's primary goal as editor-in-chief is to continue to showcase the best work in the field of affective science while also: (a) increasing Emotion's prominence in the field by promoting cutting-edge research and (b) streamlining the review process to better reflect the importance and timeliness of the published science. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

You changed my mind: Immediate and enduring impacts of social emotion regulation.

As social creatures, our relationships with other people have tremendous downstream impacts on health and well-being. However, we still know surprisingly little about how our social interactions regulate how we think and feel through life's challenges. Getting help from other people to change how one thinks about emotional events-known as "social reappraisal"-can be more effective in downregulating negative affect than reappraising on one's own, but it is unknown whether this regulatory boost from social support persists when people face the same events alone in the future. In a preregistered study of 120 young adults (N = 60 same-gender dyads, gender-split sample) involving in-lab emotion regulation tasks and a follow-up task online approximately 1 day later, we found that participants responded less negatively to aversive images that were socially regulated (i.e., reappraised with the help of a friend) both immediately and over time, as compared to images that had been solo regulated (i.e., reappraised on one's own) or not regulated (i.e., passively viewed). Interestingly, the regulatory boost from social support observed both in the lab and at follow-up was driven by women dyads. This work highlights one important mechanism explaining how support from others can facilitate emotional well-being: By changing peoples' lasting impressions of distressing events, interactions with others can help prepare them to cope with future exposure to those events on their own, underscoring how valuable others' perspectives can be when navigating ongoing emotional stressors. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Stress to inflammation and anhedonia: Mechanistic insights from preclinical and clinical models.

Anhedonia, as evidenced by impaired pleasurable response to reward, reduced reward motivation, and/or deficits in reward-related learning, is a common feature of depression. Such deficits in reward processing are also an important clinical target as a risk factor for depression onset. Unfortunately, reward-related deficits remain difficult to treat. To address this gap and inform the development of effective prevention and treatment strategies, it is critical to understand the mechanisms that drive impairments in reward function. Stress-induced inflammation is a plausible mechanism of reward deficits. The purpose of this paper is to review evidence for two components of this psychobiological pathway: 1) the effects of stress on reward function; and 2) the effects of inflammation on reward function. Within these two areas, we draw upon preclinical and clinical models, distinguish between acute and chronic effects of stress and inflammation, and address specific domains of reward dysregulation. By addressing these contextual factors, the review reveals a nuanced literature which might be targeted for additional scientific inquiry to inform the development of precise interventions.

Corticostriatal Connectivity during Prosocial Decision-making Relates to Giving Behavior during Adolescence.

Prosocial behavior during adolescence becomes more differentiated based on the recipient of the action as well as the perceived value or benefit, relative to the cost to self, for the recipients. The current study investigated how functional connectivity of corticostriatal networks tracked the value of prosocial decisions as a function of target recipient (caregiver, friend, stranger) and age of the giver, and how they related to giving behavior. Two hundred sixty-one adolescents (9-15 and 19-20 years of age) completed a decision-making task in which they could give money to caregivers, friends, and strangers while undergoing fMRI. Results indicated that adolescents were more likely to give to others as the value of the prosocial decision (i.e., the difference between the benefit to other relative to the cost to self) increased; this effect was stronger for known (caregiver and friends) than unknown targets, and increased with age. Functional connectivity between the nucleus accumbens (NAcc) and OFC increased as the value of the prosocial decisions decreased for strangers, but not for known others, irrespective of choice. This differentiated NAcc-OFC functional connectivity during decision-making as a function of value and target also increased with age. Furthermore, regardless of age, individuals who evinced greater value-related NAcc-OFC functional connectivity when considering giving to strangers relative to known others showed smaller differentiated rates of giving between targets. These findings highlight the role of corticostriatal development in supporting the increasing complexity of prosocial development across adolescence.

Peer facilitation of emotion regulation in adolescence.

Emotion regulation is particularly important for adolescents as they undergo normative developmental changes in affective systems and experience heightened risk for psychopathology. Despite a high need for emotion regulation during adolescence, commonly studied emotion regulation strategies like cognitive reappraisal are less beneficial for adolescents than adults because they rely on neural regions that are still developing during this period (i.e., lateral prefrontal cortex). However, adolescence is also marked by increased valuation of peer relationships and sensitivity to social information and cues. In the present review, we synthesize research examining emotion regulation and peer influence across development to suggest that sensitivity to peers during adolescence could be leveraged to improve emotion regulation for this population. We first discuss developmental trends related to emotion regulation at the level of behavior and brain in adolescents, using cognitive reappraisal as an exemplar emotion regulation strategy. Next, we discuss social influences on adolescent brain development, describing caregiver influence and increasing susceptibility to peer influence, to describe how adolescent sensitivity to social inputs represents both a window of vulnerability and opportunity. Finally, we conclude by describing the promise of social (i.e., peer-based) interventions for enhancing emotion regulation in adolescence.

Null results of oxytocin and vasopressin administration on mentalizing in a large fMRI sample: evidence from a randomized controlled trial.

BACKGROUND: Although potential links between oxytocin (OT), vasopressin (AVP), and social cognition are well-grounded theoretically, most studies have included all male samples, and few have demonstrated consistent effects of either neuropeptide on mentalizing (i.e. understanding the mental states of others). To understand the potential of either neuropeptide as a pharmacological treatment for individuals with impairments in social cognition, it is important to demonstrate the beneficial effects of OT and AVP on mentalizing in healthy individuals. METHODS: In the present randomized, double-blind, placebo-controlled study (n = 186) of healthy individuals, we examined the effects of OT and AVP administration on behavioral responses and neural activity in response to a mentalizing task. RESULTS: Relative to placebo, neither drug showed an effect on task reaction time or accuracy, nor on whole-brain neural activation or functional connectivity observed within brain networks associated with mentalizing. Exploratory analyses included several variables previously shown to moderate OT's effects on social processes (e.g., self-reported empathy, alexithymia) but resulted in no significant interaction effects. CONCLUSIONS: Results add to a growing literature demonstrating that intranasal administration of OT and AVP may have a more limited effect on social cognition, at both the behavioral and neural level, than initially assumed. Randomized controlled trial registrations: ClinicalTrials.gov; NCT02393443; NCT02393456; NCT02394054.

Sleep and Healthy Aging Research on Depression (SHARE-D) randomized controlled trial: Protocol overview of an experimental model of depression with insomnia, inflammation, and affect mechanisms in older adults.

Depression, one of the most common diseases in older adults, carries significant risk for morbidity and mortality. Because of the burgeoning population of older adults, the enormous burden of late-life depression, and the limited efficacy of current antidepressants in older adults, biologically plausible models that translate into selective depression prevention strategies are needed. Insomnia predicts depression recurrence and is a modifiable target to prevent incident and recurrent depression in older adults. Yet, it is not known how insomnia gets converted into biological- and affective risk for depression, which is critical for identification of molecular targets for pharmacologic interventions, and for refinement of insomnia treatments that target affective responding to improve efficacy. Sleep disturbance activates inflammatory signaling and primes immune responses to subsequent inflammatory challenge. In turn, inflammatory challenge induces depressive symptoms, which correlate with activation of brain regions implicated in depression. This study hypothesizes that insomnia serves as a vulnerability factor for inflammation-related depression; older adults with insomnia will show heightened inflammatory- and affective responding to inflammatory challenge as compared to those without insomnia. To test this hypothesis, this protocol paper describes a placebo-controlled, randomized, double-blind study of low dose endotoxin in older adults (n = 160; 60-80 y) with insomnia vs. comparison controls without insomnia. The aims of this study are to examine differences in depressive symptoms, measures of negative affective responding, and measures of positive affective responding as a function of insomnia and inflammatory challenge. If the hypotheses are confirmed, older adults with two "hits", insomnia and inflammatory activation, would represent a high risk group to be prioritized for monitoring and for depression prevention efforts using treatments that target insomnia or inflammation. Moreover, this study will inform the development of mechanism-based treatments that target affect responses in addition to sleep behaviors, and which might also be coupled with efforts to reduce inflammation to optimize efficacy of depression prevention.

The role of inflammation in acute psychosocial stress-induced modulation of reward processing in healthy female adults.

Background: Anhedonia, or loss of interest and pleasure, is a pernicious symptom of depression that involves deficits in reward processing. Stress-induced inflammation is a plausible biopsychosocial mechanism of reward deficits, but little is known whether stress-induced inflammation alters reward behavior. The present study (a secondary analysis of a completed randomized controlled trial) tested whether acute stress activated a key pro-inflammatory transcription control pathway, NF-κB, and whether this activation was associated with acute stress-induced modulation of reward processing. Methods: Healthy female adults (age 18-25) were randomized to undergo an acute psychosocial stressor (Trier Social Stress Test; n = 36) or a no-stress active control (n = 16). The Probabilistic Reward Task (PRT) (n = 30 stress; n = 12 control) was administered at baseline and at 90 min post-stress, coinciding with the peak of the stress-induced inflammatory response. Genome-wide expression profiling and bioinformatics analyses of NF-kB transcription factor activity were used to assess pro-inflammatory gene regulation. Results: Relative to the control condition, stress increased bioinformatic measures of NF-κB transcription factor activity (p = .01) and increased reward response bias scores on the PRT (p = .03). Within the stress condition, greater NF-κB activity was associated with greater increases in PRT scores (p = .01), whereas in the control condition greater NF-κB activity was associated with decreases in PRT scores (p = .002). Conclusions: Acute stress increases inflammatory signaling, and this effect is associated with increased reward processing. This demonstrates the reward system to be highly sensitive to inflammatory signaling, including the relatively mild alterations that occur following a single episode of acute psychosocial stress.

One size does not fit all: Decomposing the implementation and differential benefits of social emotion regulation strategies.

Although considerable research has demonstrated the importance of social relationships for well-being, limited work has assessed how people help regulate each other's emotions, a process called social emotion regulation. The present research utilized two experiments in 2020 (N1 = 50, N2 = 268) where people shared and responded to personal experiences to examine: (a) the kinds of regulatory support people offered others; (b) how people felt receiving different types of social feedback about their experiences; and (c) whether the support they offered others shaped how they felt receiving different feedback. When providing feedback to a confederate, participants varied in whether they chose to use validation, which affirms someone's feelings, or one of three types of social reappraisals, which help others change how they think about an emotional experience (i.e., temporal distancing: emphasizing how things change over time; positive focus: focusing on the bright side; and perspective taking: considering others' perspectives). Across studies, when participants received feedback about their own experiences, validation was the most comforting and preferred feedback. In Study 2, temporal distancing emerged as the most comforting, helpful, and preferrable type of social reappraisal and was the only reappraisal perceived as no less helpful than validation. Additionally, participants who provided social reappraisal to the confederate benefited most from receiving this type of support from others. Together, these results highlight the variability in how people use social emotion regulation strategies to support others and demonstrate how such differences in implementation, as well as individual differences in those receiving support, can shape social regulatory outcomes. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Prosocial behavior reliably reduces loneliness: An investigation across two studies.

Prosocial behavior, any behavior with the goal of benefiting another person, has been shown to improve mood and boost overall well-being for the individual performing the action as well as the recipient. The purpose of this study was to assess whether prosocial behavior could also reduce state loneliness. To examine this, we conducted two experimental studies to evaluate the effect of different prosocial behaviors on loneliness and associated cognitive and affective measures. In Study 1, we operationalized prosocial behavior as gift giving, and participants (n = 286) were randomly assigned to complete either a gift giving, gift keeping, or neutral control task. In Study 2, prosocial behavior was operationalized as writing a note of appreciation to a close other, and participants (n = 288) were randomly assigned to complete a written note of appreciation to a close other, a written reflection of a time when they received social support in the past, or a neutral control task. Across both studies, prosocial behavior reliably reduced state loneliness and improved mood but was less effective at reducing negative automatic thoughts about the self. Depressive and social anxiety symptoms were explored as possible moderators of the effects of prosocial behavior on outcome measures and were found to be significant moderators in Study 2, but not Study 1. Future directions and implications of these findings are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Associations between psychosocial factors and circulating cytokines in breast cancer survivors.

OBJECTIVE: Research has established links between social isolation and heightened levels of proinflammatory cytokines (e.g., interleukin-6 [IL-6], tumour necrosis factor alpha [TNF-α]). Recent advances allow for the examination of cytokines that may also play a role in antiviral immunity (interferon-gamma [IFN-γ]). The present work explored how various features of social experience relate to circulating cytokines in breast cancer survivors, as inflammation has been tied to cancer recurrence and mortality. DESIGN: Female breast cancer survivors (N = 43) completed a blood draw to assess circulating levels of proinflammatory cytokines (IL-6, TNF-α) and levels of a cytokine that also relates to antiviral immunity (IFN-γ). MAIN OUTCOME MEASURES: We examined associations between cytokines and different aspects of social experience, including household size, psychosocial well-being, and social threat anxiety. RESULTS: Circulating levels of IFN-γ were associated with larger household size (r = 0.32, p = 0.04) and higher levels of psychosocial well-being (r = 0.33, p = 0.04). Additionally, heightened levels of IL-6 were associated with social threat anxiety (r = 0.38, p = 0.01). Heightened IL-6 was also associated with household size (r = 0.33, p = 0.03). CONCLUSION: These findings are consistent with work suggesting that antiviral immunity and inflammation may have distinct contributions to the links between social experience and health, particularly for those previously diagnosed with breast cancer.

Sleep duration moderates the associations between immune markers and corticolimbic function during stress in adolescents.

Adolescence is characterized by biological changes in hormonal and circadian systems that, with concurrent psychosocial changes, result in increased sleep disturbances and stress sensitivity. Sleep disturbance has been associated with heightened stress sensitivity and elevated levels of inflammation in adults and adolescents, yet the neural correlates are unknown in adolescents. The current study investigated whether and how individual differences in peripheral immune markers (IL-6, TNF-α) related to neural response to stress in adolescents and whether these immune-brain associations were moderated by adolescents' sleep duration. Thirty-seven adolescents (14-15 years) who met quality control criteria for fMRI reported daily sleep duration for 7 days and performed a fMRI stressor task. A subsample of 23 adolescents additionally provided blood samples that were assayed for inflammatory markers using a multiplex assay. Results revealed that average sleep duration moderated associations between TNF-α and medial frontolimbic circuitry (amygdala, medial prefrontal cortex) during the stressor task such that, among adolescents who reported shorter sleep duration, higher levels of TNF-α were associated with greater deactivation in those regions during stress, which was associated with greater self-reported anxiety. These findings suggest that insufficient sleep duration coupled with greater levels of peripheral inflammation may promote a neural profile characterized by alterations in frontolimbic circuitry during stress, which can exacerbate sleep disturbances and/or peripheral inflammation.

Interleukin-8 and depressive responses to an inflammatory challenge: secondary analysis of a randomized controlled trial.

Emerging evidence suggests that interleukin (IL)-8 has a protective role in the context of depression. Higher levels of IL-8 are associated with lower depressive symptom severity among depressed patients, and treatment-related increases in IL-8 correlate with a positive response in depressed patients. This study (a secondary analysis of a completed randomized controlled trial) aimed to examine whether higher levels of IL-8 mitigate increases in depressed mood in response to an experimental model of inflammation induced depression. Given epidemiologic relationships identified between IL-6, tumor necrosis factor (TNF)- α, and subsequent depression, levels of these pro-inflammatory cytokines were also explored as potential moderators of depressed mood response to endotoxin. Secondary analyses were completed on data from healthy adults (n = 114) who completed a double-blind, placebo-controlled randomized trial in which participants were randomly assigned to receive either a single infusion of low-dose endotoxin (derived from Escherichia coli; 0.8 ng/kg of body weight) or placebo (same volume of 0.9% saline). IL-8, as well as IL-6 and TNF- α, were measured at baseline prior to infusion, and depressed mood and feelings of social disconnection were assessed approximately hourly. Baseline levels of IL-8, but not IL-6 or TNF-α, moderated depressed mood (ß = - 0.274, p = .03) and feelings of social disconnection (ß = - 0.307, p = .01) responses, such that higher baseline IL-8 was associated with less increase in depressed mood and feelings of social disconnection in the endotoxin, but not placebo, condition. IL-8 had threshold effects, in which highest quartile IL-8 (≥ 2.7 pg/mL) attenuated increases in depressed mood in response to endotoxin as compared to lower IL-8 quartiles (p = .02). These findings suggest that IL-8 may be a biological factor that mitigates risk of inflammation-associated depression. Clinical trials registration: ClinicalTrials.gov NCT01671150, registration date 23/08/2012.

Giving to others and neural processing during adolescence.

Adolescence is marked by an increased sensitivity to the social environment as youth navigate evolving relationships with family, friends, and communities. Prosocial behavior becomes more differentiated such that older adolescents increasingly give more to known others (e.g., family, friends) than to strangers. This differentiation may be linked with changes in neural processing among brain regions implicated in social decision-making. A total of 269 adolescents from 9-15 and 19-20 years of age completed a decision-making task in which they could give money to caregivers, friends, and strangers while undergoing functional magnetic resonance imaging (fMRI). Giving to caregivers and friends (at a cost to oneself) increased with age, but giving to strangers remained lower and stable across age. Brain regions implicated in cognitive control (dorsolateral and ventrolateral prefrontal cortex) showed increased blood-oxygen-level-dependent (BOLD) activation with increasing age across giving decisions to all recipients; regions associated with reward processing (ventral striatum and ventral tegmental area) showed increased activation across all ages when giving to all recipients. Brain regions associated with social cognition were either not active (dorsomedial prefrontal cortex) or showed reduced activation (temporal parietal junction and posterior superior temporal sulcus) when giving to others across all ages. Findings have implications for understanding the role of brain development in the increased complexity of social decision-making during adolescence.

Exploring the effect of loneliness on fear: Implications for the effect of COVID-19-induced social disconnection on anxiety.

The consequences of the COVID-19 pandemic have resulted in many disruptions to daily life, including an abrupt increase in social disconnection. As measures were put in place to combat the spread of COVID-19, people across the globe began living in states of limited social contact, fostering feelings of social isolation and loneliness. Previous literature suggests that these increases in social disconnection can have profound effects on both physical and mental health, perhaps especially in the case of fear disorders. The combination of feeling disconnected from others and the high level of daily threat experienced due to COVID-19 created conditions under which dysfunctional and persistent fears were especially likely to develop. Building on current understanding of the harmful effects of social disconnection on well-being in general as well as specific implications for fear, here we present findings from three preliminary investigations that are the first to directly examine the effects of loneliness on how fears are learned and maintained. The Results of this work show that loneliness impairs the process by which fears are extinguished, which is central to both the regulation of fear and treatment of fear disorders, and provide insight into potential avenues to mitigate such effects.

Frontostriatal functional connectivity underlies self-enhancement during social evaluation.

Self-enhancement, the tendency to view oneself positively, is a pervasive social motive widely investigated in the psychological sciences. Relatively little is known about the neurocognitive mechanisms underlying this motive, specifically in social-evaluative situations. To investigate whether positive emotion regulation circuitry, circuitry involved in modulating positive affect, relates to the self-enhancement motive in social contexts, we conducted an functional magnetic resonance imaging (fMRI) study in a healthy young adult sample. We hypothesized that self-enhancement indices (state and trait self-esteem) would relate to greater functional connectivity between right ventrolateral prefrontal cortex (RVLPFC), a region implicated in emotion regulation, and the ventral striatum (VS), a region associated with reward-related affect, during a social feedback task. Following social evaluation, participants experienced stable or decreased state self-esteem. Results showed that stable state self-esteem from pre- to post-scan and higher trait self-esteem related to greater RVLPFC-VS connectivity during positive evaluation. Stable-state self-esteem also related to greater RVLPFC-VS connectivity during negative evaluation. Moreover, RVLPFC activation during all types of feedback processing and left VS activation during negative feedback processing was greater for participants with stable-state self-esteem. These findings implicate neurocognitive mechanisms underlying emotion regulation in the self-enhancement motive and highlight a pathway through which self-enhancement may restore feelings of self-worth during threatening situations.

Reclassifying the Unique Inhibitory Properties of Social Support Figures: A Roadmap for Exploring Prepared Fear Suppression.

Recent work has revealed that social support cues are powerful inhibitors of the fear response. They are endowed with a unique combination of inhibitory properties, enabling them to both inhibit fear in the short term and reduce fear in the long term. While these findings had previously been thought to suggest that social support cues belong to a category of prepared safety stimuli, mounting evidence clearly shows that the mechanisms underlying safety signaling cannot account for the unique effects of social support cues. Here, we propose a reclassification of social support cues as members of a prepared fear suppressor category. We present an argument for the prepared fear suppressor classification, discuss potential mechanisms underlying the unique effects of prepared fear suppressors, and outline next steps to build an understanding of this category and its clinical implications. This review is meant to serve as a roadmap for exploring this novel category of prepared fear suppressors, whose never-before-seen range of inhibitory effects makes them an important and impactful discovery with implications for both fear learning theory and clinical application.

Ventromedial prefrontal cortex activity differentiates sick from healthy faces: Associations with inflammatory responses and disease avoidance motivation.

BACKGROUND: Humans are able to discern the health status of others using olfactory and visual cues, and subsequently shift behavior to make infection less likely. However, little is known about how this process occurs. The present study examined the neural regions involved in differentiating healthy from sick individuals using visual cues. METHODS: While undergoing a functional magnetic resonance imaging scan, participants (N = 42) viewed facial photos of 30 individuals (targets) who had been injected with an inflammatory challenge--low-dose endotoxin (i.e., sick) or placebo (i.e., healthy), and rated how much they liked each face. We examined regions implicated in processing either threat (amygdala, anterior insula) or cues that signal safety (ventromedial prefrontal cortex [VMPFC]), and how this activity related to their liking of targets and cytokine levels (interleukin-6, tumor necrosis factor-α) exhibited by the targets. RESULTS: Photos of sick faces were rated as less likeable compared to healthy faces, and the least liked faces were those individuals with the greatest inflammatory response. While threat-related regions were not significantly active in response to viewing sick faces, the VMPFC was more active in response to viewing healthy (vs. sick) faces. Follow-up analyses revealed that participants tended to have lower VMPFC activity when viewing the least liked faces and the faces of those with the greatest inflammatory response. CONCLUSIONS: This work builds on prior work implicating the VMPFC in signaling the presence of safe, non-threatening visual stimuli, and suggests the VMPFC may be sensitive to cues signaling relative safety in the context of pathogen threats.