Discrimination and Cardiovascular Health in Black Americans: Exploring Inflammation as a Mechanism and Perceived Control as a Protective Factor.

OBJECTIVE: Inflammation may be an integral physiological mechanism through which discrimination impacts cardiovascular health and contributes to racial health disparities. Limited research has examined psychosocial factors that protect against the negative effects of discrimination on inflammation. Perceived control is a promising possible protective factor, given that it has been shown to moderate the relationship between other psychosocial stressors and physiological outcomes. This study thus tested whether systemic inflammation mediated the link between discrimination and cardiovascular health and whether perceived control moderated this relationship. METHODS: Data for this project included 347 non-Hispanic/Latinx Black adults (mean [standard deviation] age = 51.64 [11.24] years; 33% female) taken from the Midlife in the United States study. Perceived control and daily discrimination were assessed via self-report, and inflammation was measured via circulating levels of C-reactive protein (CRP), interleukin-6 (IL-6), fibrinogen, and tumor necrosis factor α. Cardiovascular health was measured by morbidity of cardiovascular conditions: heart disease, hypertension, and/or stroke. RESULTS: CRP (indirect effect: b = 0.004, 95% confidence interval [CI] = 0.001-0.007) and fibrinogen (indirect effect: b = 0.002, 95% CI = 0.0003-0.005) mediated the link between discrimination and cardiovascular conditions. Perceived control moderated the relationship between discrimination and CRP ( F (1, 293) = 4.58, Δ R2 = 0.013, b = -0.02, SE = 0.01, p = .033). CRP mediated the link between discrimination and cardiovascular conditions only for those who reported low levels of perceived control (Index = -0.003, 95% CI = -0.007 to -0.0001). CONCLUSION: Findings provide empirical evidence of inflammation as a mechanism linking discrimination to cardiovascular conditions among Black Americans. Additionally, perceived control may be protective. Findings could suggest beliefs about control as a potential intervention target to help reduce the negative effects of discrimination on cardiovascular health among Black Americans.

Differential effects of social versus monetary incentives on inhibitory control under acute inflammation.

While the impact of chronic, low-grade inflammation on cognitive functioning is documented in the context of neurodegenerative disease, less is known about the association between acute increases in inflammation and cognitive functioning in daily life. This study investigated how changes in interleukin-6 (IL-6) levels were associated with performance on an inhibitory control task, the go/no-go task. We further examined whether the opportunity to earn different incentive types (social or monetary) and magnitudes (high or low) was associated with differential performance on the task, depending on IL-6 levels. Using a within-participant design, individuals completed an incentivized go/no-go task before and after receiving the annual influenza vaccine. Multilevel logistic regressions were performed on the trial-level data (Nobs = 30,528). For no-go trials, we did not find significant associations between IL and 6 reactivity between the sessions and changes in trial accuracy. For go trials, we found significant differences in the associations between IL and 6 reactivity and changes in accuracy from session 1 to session 2 as a function of the incentive condition. Notably, greater IL-6 reactivity was consistently associated with fewer omission errors (i.e., greater accuracy on go trials) on high-magnitude social incentives (i.e., viewing a picture of a close-other picture) when compared to both low-magnitude social and high-magnitude monetary incentives. Together, these results suggest that mild fluctuations in inflammation might alter the valuation of an incentive, and possibly a shift toward devoting greater attentional resources when a large social incentive is on the line. Overall, this study sheds light on how everyday, low-grade fluctuations in inflammation may influence cognitive abilities essential for daily life and effective inhibitory control.

The roles of inflammation, affect, and interoception in predicting social perception.

"Sickness behavior" is an orchestrated suite of symptoms that commonly occur in the context of inflammation, and is characterized by changes in affect, social experience, and behavior. However, recent evidence suggests that inflammation may not always produce the same set of sickness behavior (e.g., fatigue, anhedonia, and social withdrawal). Rather, inflammation may be linked with different behavior across contexts and/or across individuals, though research in this area is under-developed to-date. In the present study (n = 30), we evaluated the influence of affective context and individual differences in difficulty detecting bodily sensations (i.e., interoceptive difficulty) on social perception following an inflammatory challenge. Inflammation was induced using the influenza vaccine and inflammatory reactivity was operationalized as changes in circulating levels of interleukin-6 (IL-6) before the vaccine and approximately 24 h later. Twenty-four hours after administration of the influenza vaccine, we manipulated affective context using a well-validated affect misattribution task in which participants made trustworthiness judgments of individuals with neutral facial expressions following the rapid presentation of "prime" images that were positive or negative in affective content. Interoceptive difficulty was measured at baseline using a validated self-report measure. Results revealed significant interactions between inflammatory reactivity to the influenza vaccine and affective context on social perception. Specifically, individuals with greater inflammatory reactivity were more biased by affective context when judging the trustworthiness of neutral faces. In addition, interoceptive difficulty and affective context interacted to predict social perception such that individuals with greater interoceptive difficulty were more biased by affective context in these judgments. In sum, we provide some of the first evidence that inflammation may amplify the saliency of affective cues during social decision making. Our findings also replicate prior work linking interoceptive ability to the use of affect-as-information during social perception, but in the novel context of inflammation.

What Does the MacArthur Scale of Subjective Social Status Measure? Separating Economic Circumstances and Social Status to Predict Health.

BACKGROUND: Subjective socioeconomic status is robustly associated with many measures of health and well-being. The MacArthur Scale of Subjective Social Status (i.e., the MacArthur ladder) is the most widely used measure of this construct, but it remains unclear what exactly the MacArthur ladder measures. PURPOSE: The present research sought to explore the social and economic factors that underlie responses to the MacArthur ladder and its relationship to health. METHODS: We investigated this issue by examining the relationship between scores on the MacArthur ladder and measures of economic circumstances and noneconomic social status, as well as health and well-being measures, in healthy adults in the USA. RESULTS: In three studies (total N = 1,310) we found evidence that economic circumstances and social status are distinct constructs that have distinct associations with scores on the MacArthur ladder. We found that both factors exhibit distinct associations with measures of health and well-being and accounted for the association between the MacArthur ladder and each measure of health and well-being. CONCLUSIONS: Our findings suggest that the MacArthur ladder's robust predictive validity may result from the fact that it measures two factors-economic circumstances and social status-that are each independently associated with health outcomes. These findings provide a novel perspective on the large body of literature that uses the MacArthur ladder and suggests health researchers should do more to disentangle the social and economic aspects of subjective socioeconomic status.

Past research has found that people's subjective perception of their own socioeconomic status (SES) is associated with their health and well-being, even after controlling for traditional measures of SES such as income. But researchers still do not know why. One possibility is that subjective SES is simply a different measure of SES. Another is that it measures social status, separate from economic circumstances. We investigated this question using the MacArthur Scale of Subjective Social Status, which measures how people see their place in society. Across three studies using 1,300 adults in the USA, we found that the MacArthur Ladder measures two distinct factors: (i) economic circumstances, as measured by their income, education, housing, etc. and (ii) social status as measured by relative judgements of power, control, social influence, and their standing in their community and society. Both of these aspects of SES uniquely predict health and well-being. Our investigation demonstrates that the MacArthur ladder is good at predicting health outcomes because it measures both economic circumstances and social status. This new insight can help health researchers better understand the effects of social and economic factors on health, and to measure them more precisely.

Support-Giving Is Associated With Lower Systemic Inflammation.

BACKGROUND: Support-giving has emerged as a health-relevant social behavior, such that giving more support is associated with better physical health. However, biological mechanisms by which support-giving and health are linked remain unclear. Whether support-giving uniquely relates to health relative to other psychosocial factors is also an open research question. PURPOSE: Two studies test the hypothesis that support-giving is uniquely (over-and-above other psychosocial factors) related to lower systemic inflammation, a biological correlate of health. METHODS: Cross-sectional associations of support-giving with markers of systemic inflammation (i.e., interleukin-6 [IL-6], C-reactive protein [CRP]) were examined in two independent samples of midlife adults (Study 1, n = 746; Study 2, n = 350). RESULTS: Consistent with hypotheses, giving to more social targets (to family and friends, and also volunteering for various causes), but not receiving support from similar targets, was associated with lower IL-6. In conceptual replication and extension with a different measure of support-giving, higher frequency of support-giving behavior was associated with lower IL-6, even after adjusting for social network size and individual differences in social desirability. There were no associations between support-giving and CRP in either sample. CONCLUSIONS: Future research needs to establish causality and directly test mechanistic pathways, but together, findings reaffirm the health-relevance of support-giving behavior and shed light on a promising biological mechanism by which such effects may occur.

Support-giving behavior and health are linked such that more support-giving is related to better health and longevity for the person giving. How such a link occurs, however, is an open question for research. Two cross-sectional studies test the hypothesis that support-giving behavior relates to lower systemic inflammation, a potential biological pathway linking supportive behavior with health. Results of Study 1 show that giving to more social targets (to family and friends, and also volunteering) is associated with lower inflammation. Receiving support was not associated with inflammation. In a replication and extension, Study 2 shows that a greater frequency of giving is also related to lower systemic inflammation, over and above the size of one's social network and individual differences in reporting socially desirable responses. Although more research is needed to establish whether support-giving causes systemic inflammation to change, the current findings highlight a promising pathway by which support-giving behavior benefits health.

Lower Socioeconomic Position Is Associated with Greater Activity in and Integration within an Allostatic-Interoceptive Brain Network in Response to Affective Stimuli.

Socioeconomic inequities shape physical health and emotional well-being. As such, recent work has examined the neural mechanisms through which socioeconomic position (SEP) may influence health. However, there remain critical gaps in knowledge regarding the relationships between SEP and brain function. These gaps include a lack of research on: (1) the association between SEP and brain functioning in later life, (2) relationships between SEP and functioning of the whole brain beyond specific regions of interest, and (3) how neural responses to positive affective stimuli differ by SEP. The current study addressed these gaps by examining the association between SEP (i.e., education, income) and neural responses to affective stimuli among 122 mid- to late-life adults. During MRI scanning, participants viewed 30 positive, 30 negative, and 30 neutral images; activation and network connectivity analyses explored associations between SEP and neural responses to these affective stimuli. Analyses revealed that those with lower SEP showed greater neural activity to both positive and negative images in regions within the allostatic-interoceptive network, a system of regions implicated in representing and regulating physiological states of the body and the external environment. There were no positive associations between SEP and neural responses to negative or positive images. In addition, graph-theory network analyses showed that individuals with lower SEP demonstrated greater global efficiency within the allostatic-interoceptive network and executive control network, across all task conditions. The findings suggest that lower SEP is associated with enhanced neural sensitivity to affective cues that may be metabolically costly to maintain over time and suggest a mechanism by which SEP might get "under the skull" to influence mental and physical well-being.

Inflammatory reactivity to the influenza vaccine is associated with changes in automatic social behavior.

Recent evidence suggests differential patterns of social behavior following an inflammatory challenge, such that increases in inflammation may not uniformly lead to social withdrawal. Indeed, increases in inflammation have been associated with enhanced self-reported motivation to approach a specific close other, and greater neural sensitivity to positive social cues. However, no known studies have examined the association between inflammation in response to an inflammatory challenge and social behavior in humans, nor has past research examined specifically how approach and withdrawal behavior may differ based on whether the target is a close other or stranger. To address this, 31 participants (ages 18-24) received the influenza vaccine to elicit a low-grade inflammatory response. The morning before and approximately 24 h after the vaccine, participants provided a blood sample and completed a computer task assessing automatic (implicit) approach and withdrawal behavior toward a social support figure and strangers. Greater increases in the inflammatory cytokine interleukin-6 (IL-6) in response to the vaccine were associated with an increase in accuracy in avoiding strangers and a decrease in accuracy in approaching them. Increases in IL-6 were also associated with a decrease in reaction time to approach a support figure, but only when controlling for baseline IL-6 levels. There were no associations between change in IL-6 and changes in self-reported motivation to engage in social behavior with either close others, or strangers. Together, these findings reveal that increases in inflammation following the influenza vaccine are associated with automatic social behavior, especially behavior suggesting avoidance of unfamiliar social targets and ease in approaching a support figure. These data add to the growing literature suggesting that the association between inflammation and social behavior includes both social withdrawal and social approach, depending on the specific target.

ß-Adrenergic Contributions to Emotion and Physiology During an Acute Psychosocial Stressor.

OBJECTIVE: ß-Adrenergic receptor signaling, a critical mediator of sympathetic nervous system influences on physiology and behavior, has long been proposed as one contributor to subjective stress. However, prior findings are surprisingly mixed about whether ß-blockade (e.g., propranolol) blunts subjective stress, with many studies reporting no effects. We reevaluated this question in the context of an acute psychosocial stressor with more comprehensive measures and a larger-than-typical sample. We also examined the effects of ß-blockade on psychophysiological indicators of sympathetic and parasympathetic nervous system reactivity, given that ß-blockade effects for these measures specifically under acute psychosocial stress are not yet well established. METHODS: In a double-blind, randomized, placebo-controlled study, 90 healthy young adults received 40 mg of the ß-blocker propranolol or placebo. Participants then completed the Trier Social Stress Test, which involved completing an impromptu speech and difficult arithmetic in front of evaluative judges. Self-reported emotions and appraisals as well as psychophysiology were assessed throughout. RESULTS: Propranolol blunted Trier Social Stress Test preejection period reactivity (b = 9.68, p = .003), a marker of sympathetic nervous system activity, as well as salivary α-amylase reactivity (b = -0.50, p = .006). Critically, propranolol also blunted negative, high arousal emotions in response to the stressor (b = -0.22, p = .026), but cognitive appraisals remained intact (b values < -0.17, p values > .10). CONCLUSIONS: These results provide updated experimental evidence that ß-adrenergic blockade attenuates negative, high arousal emotions in response to a psychosocial stressor while also blunting sympathetic nervous system reactivity. Together, these findings shed light on the neurophysiological mechanisms by which stressors transform into the subjective experience we call "stress."Trial Registration: ClinicalTrials.gov Identifier: NCT02972554.

Socioeconomic status and inflammation: a meta-analysis.

Socioeconomic status (SES), often conceptualized as income, education, or occupation, is associated with risk for disease morbidity and psychopathology. Recent research has focused on the potential biological mechanisms linking lower SES and poor outcomes; much of this work has examined the relationship between SES and markers of systemic inflammation. The strength of the estimated association between SES and inflammatory markers varies widely across individual studies. Thus, we used meta-analytic techniques to quantify the magnitude of this relationship. To accomplish this, PubMed and PsycINFO were searched for papers that reported on SES and two commonly measured systemic inflammatory markers, C-reactive protein (CRP) and interleukin-6 (IL-6). Peer-reviewed, empirical papers conducted in non-patient populations were included. Data from 43 papers (N = 111,156) reporting a total of 63 relevant effect sizes were included in analyses. SES, broadly defined, was significantly associated with both levels of CRP (Z = 0.12; 95% CI, 0.09-0.16) and IL-6 (Z = 0.15; 95% CI, 0.12-0.18); individuals with lower SES showed higher levels of systemic inflammation. Subanalyses demonstrated that studies operationalizing SES as either levels of income or educational attainment also found significant associations with both CRP and IL-6. Moderator analyses revealed that effect sizes varied based on sample characteristics and analysis approaches. Lower SES is associated with significantly elevated levels of inflammatory markers of disease risk. Thus, pro-inflammatory pathways are likely an important mechanism translating socioeconomic inequalities into mental and physical health disparities.

A Preliminary Investigation of Psychoneurological Symptoms in Low-Income Mothers.

BACKGROUND: Exposure to chronic stressors may contribute to the development of psychoneurological symptoms (i.e., fatigue, cognitive dysfunction, sleep disturbance, depressed mood, and pain) that can compromise maternal function. OBJECTIVES: In two studies of low-income mothers, we investigated the presence of psychoneurological symptoms and explored associations between mothers' stressors and psychoneurological symptoms as well as between symptoms and function. We also considered the possible mediating role of the symptoms between stressors and function. METHODS: We conducted secondary analyses of psychoneurological symptoms in two studies of low-income mothers of infants and toddlers in the United States. Study 1 sampled Latina women with limited English proficiency, whereas Study 2 was conducted with English-speaking women from diverse backgrounds. In both studies, symptoms were measured using items from the Center for Epidemiological Studies Depression Scale and the Medical Outcomes Study Short-Form Health Survey. Maternal function was measured through self-report and researcher observation. In Study 2, stressors were measured using the Everyday Stressors Index. Multiple linear regressions were used to investigate associations while controlling for relevant covariates. RESULTS: In both studies, mothers endorsed a wide range of psychoneurological symptoms. In Study 1, psychoneurological symptoms had significant negative associations with role function, social function, and developmental stimulation. In Study 2, psychoneurological symptoms had significant negative associations with role function, social function, and physical function. Using Aroian test for mediation, we found that psychoneurological symptoms mediated all significant relationships between stressors and maternal functions in Study 2. DISCUSSION: In two samples of low-income mothers, psychoneurological symptoms were prevalent and associated with chronic stressors and with maternal function and may mediate the association between those two factors. These findings extend prior research on depressive symptoms in mothers by investigating pain as an additional key symptom. The studies advance symptom science by highlighting psychoneurological symptoms in a heterogeneous sample without known health conditions.

Role Fulfillment Mediates the Association Between Daily Family Assistance and Cortisol Awakening Response in Adolescents.

Family assistance (helping the family) is associated with both positive and negative psychological and biological outcomes during adolescence. However, the association between family assistance and the hypothalamic-pituitary-adrenal (HPA) axis remains unstudied. Thus, we assess how helping the family relates to adolescents' diurnal cortisol, an index of HPA activity, and psychological outcomes. Three hundred and seventy ethnically diverse adolescents (ages 11-18) reported daily helping behaviors and psychological experiences for 14 days and provided four saliva samples per day for 4 days. Multilevel modeling revealed that cortisol awakening response was lower the day after adolescents helped their families more. This association was explained, in part, by perceived role fulfillment (feeling like a good son, daughter, and sibling). Results highlight a possible psychological and biological benefit of assisting the family during adolescence.

Two Methods for Calculating Symptom Cluster Scores.

BACKGROUND: Symptom clusters are conventionally distilled into a single score using composite scoring, which is based on the mathematical assumption that all symptoms are equivalently related to outcomes of interest; this may lead to a loss of important variation in the data. OBJECTIVES: This article compares two ways of calculating a single score for a symptom cluster: a conventional, hypothesis-driven composite score versus a data-driven, reduced rank regression score that weights the symptoms based on their individual relationships with key outcomes. METHODS: We conducted a secondary analysis of psychoneurological symptoms from a sample of 356 low-income mothers. Four of the psychoneurological symptoms (fatigue, cognitive dysfunction, sleep disturbance, and depressed mood) were measured with the Center for Epidemiological Studies Depression Scale; the fifth (pain) was measured using an item from the Medical Outcomes Study 12-item Short Form Health Survey (SF-12). Mothers' function was measured using the 12-item Short Form Health Survey. The composite score was calculated by summing standardized scores for each individual psychoneurological symptom. In contrast, reduced rank regression weighted the individual symptoms using their respective associations with mothers' function; the weighted individual symptom scores were summed into the reduced rank regression symptom score. RESULTS: The composite score and reduced rank regression score were highly correlated at .93. The cluster of psychoneurological symptoms accounted for 53.7% of the variation in the mothers' function. Depressed mood and pain accounted for almost all the explained variation in mothers' function at 37.2% and 15.0%, respectively. DISCUSSION: The composite score approach was simpler to calculate, and the high correlation with the reduced rank regression score indicates that the composite score reflected most of the variation explained by the reduced rank regression approach in this data set. However, the reduced rank regression analysis provided additional information by identifying pain and depressed mood as having the strongest association with a mother's function, which has implications for understanding which symptoms to target in future interventions. Future studies should also explore composite versus reduced rank regression approaches given that reduced rank regression may yield different insights in other data sets.

Motivation, Belongingness, and Anxiety in Neuroscience Undergraduates: Emphasizing First-Generation College Students.

The growth of undergraduate neuroscience programs nation-wide demonstrates that interest in this field is escalating. By understanding what motivates neuroscience undergraduates to do well and how they generally feel toward their major and environment, educators will be better able to attend to the needs of their neuroscience students. Thus, the present study aimed to characterize the psychosocial profiles of neuroscience majors in the U.S., with a particular interest in potential differences by generation in college, school type, and gender. For this, U.S. institutions that offer a neuroscience major were identified, and program directors/coordinators were asked to share a study survey with neuroscience majors at their school. The survey, which included demographics and measures of motivation, sense of belongingness, and anxiety, was completed by 756 students from 69 different institutions. Results showed that first-generation college students had lower academic performance (i.e., GPA), which was mediated by differences in motivation, and test- and trait-anxiety. Further, students from Liberal Arts Colleges reported valuing neuroscience courses more than students at National Universities, and the desire to meet others expectations, value of neuroscience course work, and anxiety were higher among female neuroscience students than males. Finally, test-anxiety was the strongest correlate of academic performance. These insights help identify potential targets for developing new teaching and advising strategies that could be employed to facilitate success among all neuroscience undergraduates.

Subjective social status and neural processing of race in Mexican American adolescents.

Adolescence is a sensitive period for sociocultural development in which facets of social identity, including social status and race, become especially salient. Despite the heightened importance of both social status and race during this developmental period, no known work has examined how individual differences in social status influence perceptions of race in adolescents. Thus, in the present study, we investigated how both subjective social status and objective socioeconomic status (SES) influence neural responses to race. Twenty-three Mexican American adolescents (15 females; mean age = 17.22 years) were scanned using functional magnetic resonance imaging while they viewed Black and White faces in a standard labeling task. Adolescents rated their subjective social status in US society, while their parents responded to questions about their educational background, occupation, and economic strain (objective SES). Results demonstrated a negative association between subjective social status and neural responses in the amygdala, fusiform face area, and medial prefrontal cortex when adolescents viewed Black (relative to White) faces. In other words, adolescents with lower subjective social status showed greater activity in neural regions involved in processing salience, perceptual expertise, and thinking about the minds of others when they viewed images of Black faces, suggesting enhanced salience of race for these youth. There was no relationship between objective SES and neural responses to the faces. Moreover, instructing participants to focus on the gender or emotion expression on the face attenuated the relationship between subjective social status and neural processing of race. Together, these results demonstrate that subjective social status shapes the way the brain responds to race, which may have implications for psychopathology.

Self-Affirmation Activates the Ventral Striatum: A Possible Reward-Related Mechanism for Self-Affirmation.

Self-affirmation (reflecting on important personal values) has been shown to have a range of positive effects; however, the neural basis of self-affirmation is not known. Building on studies showing that thinking about self-preferences activates neural reward pathways, we hypothesized that self-affirmation would activate brain reward circuitry during functional MRI (fMRI) studies. In Study 1, with college students, making judgments about important personal values during self-affirmation activated neural reward regions (i.e., ventral striatum), whereas making preference judgments that were not self-relevant did not. Study 2 replicated these results in a community sample, again showing that self-affirmation activated the ventral striatum. These are among the first fMRI studies to identify neural processes during self-affirmation. The findings extend theory by showing that self-affirmation may be rewarding and may provide a first step toward identifying a neural mechanism by which self-affirmation may produce a wide range of beneficial effects.

Links between inflammation, amygdala reactivity, and social support in breast cancer survivors.

Psychosocial stress can affect inflammatory processes that have important consequences for cancer outcomes and the behavioral side effects of cancer treatment. To date, however, little is known about the upstream neural processes that may link psychosocial stressors and inflammation in cancer patients and survivors. To address this issue, 15 women who had been diagnosed with early-stage breast cancer and completed cancer treatment and 15 age- and ethnicity-matched women with no cancer history were recruited for a neuroimaging study. Participants provided a blood sample for levels of circulating inflammatory markers (CRP and IL-6), underwent an fMRI scan in which they completed a threat reactivity task designed to elicit activity in the amygdala, and reported their levels of perceived social attachment/support. There were no significant differences between cancer survivors and controls in levels of CRP or IL-6, in amygdala reactivity to the socially threatening images, or in levels of perceived social support. However, results showed a strong, positive correlation between CRP concentration and left amygdala reactivity in the survivor group that was not apparent in controls. Higher levels of social support in the survivor group were also associated with reduced amygdala reactivity and CRP. These data suggest the possibility of a stronger "neural-immune pipeline" among breast cancer survivors, such that peripheral inflammation is more strongly associated with neural activity in threat-related brain regions.

Exposure to an inflammatory challenge enhances neural sensitivity to negative and positive social feedback.

Inflammation, part of the body's innate immune response, can lead to "sickness behaviors," as well as alterations in social and affective experiences. Elevated levels of pro-inflammatory cytokines have been associated with increased neural sensitivity to social rejection and social threat, but also decreased neural sensitivity to rewards. However, recent evidence suggests that inflammation may actually enhance sensitivity to certain social rewards, such as those that signal support and care. Despite a growing interest in how inflammation influences neural reactivity to positive and negative social experiences, no known studies have investigated these processes in the same participants, using a similar task. To examine this issue, 107 participants were randomly assigned to receive either placebo or low-dose endotoxin, which safely triggers an inflammatory response. When levels of pro-inflammatory cytokines were at their peak, participants were scanned using fMRI while they received positive, negative, and neutral feedback from an "evaluator" (actually a confederate) about how they came across in an audio-recorded interview. In response to negative feedback (vs. neutral), participants in the endotoxin condition showed heightened neural activity in a number of threat-related neural regions (i.e., bilateral amygdala, dorsal anterior cingulate cortex) and a key mentalizing-related region (i.e., dorsomedial PFC), compared to placebo participants. Interestingly, when receiving positive feedback (vs. neutral), endotoxin (vs. placebo) led to greater neural activity in the ventral striatum and ventromedial PFC, regions often implicated in processing reward, as well as greater activity in dorsomedial PFC. Together, these results reveal that individuals exposed to an inflammatory challenge are more "neurally sensitive" to both negative and positive social feedback, suggesting that inflammation may lead to a greater vigilance for both social threats and social rewards.

The role of the ventral striatum in inflammatory-induced approach toward support figures.

Although considerable research has shown that inflammation leads to social withdrawal more generally, it is also possible that inflammation leads to social approach when it comes to close others. Whereas it may be adaptive to withdraw from strangers when sick, it may be beneficial to seek out close others for assistance, protection, or care when sick. However, this possibility has never been explored in humans nor have the neural substrates of these behavioral changes. Based on the role of the ventral striatum (VS) in responding to: (1) the anticipation of and motivation to approach rewarding outcomes and (2) viewing social support figures, the VS may also be involved in sickness-induced approach toward support figures. Thus, the goal of the present study was to examine whether inflammation leads to a greater desire to approach support figures and greater VS activity to viewing support figures. To examine this, 63 participants received either placebo or low-dose endotoxin, which safely triggers an inflammatory response. Participants reported how much they desired to be around a self-identified support figure, and viewed pictures of that support figure while undergoing an fMRI scan to assess reward-related neural activity. In line with hypotheses, endotoxin (vs. placebo) led participants to report a greater desire to be around their support figure. In addition, endotoxin (vs. placebo) led to greater VS activity to images of support figures (vs. strangers), and greater increases in inflammation (IL-6 levels) were associated with greater increases in VS activity. Together, these results reveal a possible neural mechanism important for sickness-induced social approach and highlight the need for a more nuanced view of changes in social behavior during sickness.

Greater amygdala activity and dorsomedial prefrontal-amygdala coupling are associated with enhanced inflammatory responses to stress.

Psychological stress is implicated in the etiology of many common chronic diseases and mental health disorders. Recent research suggests that inflammation may be a key biological mediator linking stress and health. Nevertheless, the neurocognitive pathways underlying stress-related increases in inflammatory activity are largely unknown. The present study thus examined associations between neural and inflammatory responses to an acute laboratory-based social stressor. Healthy female participants (n=31) were exposed to a brief episode of stress while they underwent an fMRI scan. Blood samples were taken before and after the stressor, and plasma was assayed for markers of inflammatory activity. Exposure to the stressor was associated with significant increases in feelings of social evaluation and rejection, and with increases in levels of inflammation. Analyses linking the neural and inflammatory data revealed that heightened neural activity in the amygdala in response to the stressor was associated with greater increases in inflammation. Functional connectivity analyses indicated that individuals who showed stronger coupling between the amygdala and the dorsomedial prefrontal cortex (DMPFC) also showed a heightened inflammatory response to the stressor. Interestingly, activity in a different set of neural regions was related to increases in feelings of social rejection. These data show that greater amygdala activity in response to a stressor, as well as tighter coupling between the amygdala and the DMPFC, are associated with greater increases in inflammatory activity. Results from this study begin to identify neural mechanisms that might link stress with increased risk for inflammation-related disorders such as cardiovascular disease and depression.