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.

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.

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.

Associations between amygdala reactivity to social threat, perceived stress and C-reactive protein in breast cancer survivors.

Chronic inflammation in women diagnosed with breast cancer is critically linked with tumor progression, metastasis and survival. C-reactive protein (CRP)-a circulating marker of inflammation-is an important prognostic marker for cancer-related outcomes in breast cancer survivors (e.g. recurrence, fatigue). Psychological stress, which increases circulating markers of inflammation following sympathetic nervous system (SNS) activation, may modulate tumor-relevant inflammatory processes. However, little is known about neural mechanisms that might link stress and downstream SNS-initiated proinflammatory processes, such as elevated CRP. Past work suggests that threat-related neural regions, such as the amygdala, may be key in translating psychological stress into SNS activity and subsequent peripheral inflammation. Thus, we examined amygdala reactivity to socially threatening stimuli in association with perceived stress and plasma CRP levels to further elucidate neuro-immune pathways of social threat processing within breast cancer survivors (N = 37). Significant positive correlations were found between left amygdala reactivity in response to socially threatening stimuli (e.g. angry/fearful faces vs happy faces) and perceived stress in the previous month (r = 0.32, P = 0.025) and between left amygdala reactivity and CRP (r = 0.33, P = 0.025). This work builds on prior research implicating the amygdala as a key structure in crosstalk between threat-related neural circuitries and peripheral inflammation, particularly within cancer survivors.

Two Distinct Immune Pathways Linking Social Relationships With Health: Inflammatory and Antiviral Processes.

OBJECTIVE: Social relationships can both influence and be influenced by immune processes. Past work implicates two distinct pathways along which this interaction may occur: inflammatory processes and antiviral processes. This article reviews how social behavior is modulated by these two immune processes and how such processes may in turn regulate social behavior. METHODS: This narrative review outlines existing work on social behavior and both inflammatory and antiviral processes. We propose an evolutionary framework that aims to integrate these findings. Specifically, social isolation has evolutionarily increased the likelihood of wounding and therefore increased the need for inflammation, which works to promote healing. Conversely, broader social networks provide protection from physical threats but also lead to increased pathogen exposure, necessitating a more robust antiviral response. RESULTS: This review highlights that social adversity, such as social exclusion or loneliness, is associated with increased inflammation, whereas social contact is associated with increased antiviral immunity. Furthermore, increased inflammation leads to sensitivity to social stimuli, presumably to avoid hostile conspecifics and approach allies who may provide care while vulnerable. Individuals with inadequate antiviral immunity engage in behaviors that minimize pathogen exposure, such as reduced affiliative behavior. CONCLUSIONS: This review suggests that adverse social experiences (social isolation, perceived social threat) may induce inflammatory responses while suppressing antiviral immunity, whereas positive experiences of social connection may reduce inflammation and bolster antiviral responses. Although acutely elevated inflammation would be adaptive under conditions where wounding is likely, chronic inflammation related to continued social adversity may have detrimental health consequences.

The role of social relationships in the link between olfactory dysfunction and mortality.

Recent work suggests that olfactory dysfunction is a strong predictor of five-year mortality in older adults. Based on past work showing: 1) that olfactory dysfunction impairs social functioning and 2) that social ties are linked with mortality, the current work explored whether impairments in social life mediated the relationship between olfactory dysfunction and mortality. Additionally, based on work showing gender differences in the social consequences of olfactory dysfunction, gender was assessed as a potential moderator of this association. Social network size mediated the olfactory-mortality link for females. To probe what feature of social networks was driving this effect, we investigated two subcomponents of social life: emotional closeness (e.g., perceived social support, loneliness) and physical closeness (e.g., physical contact, in-person socializing with others). Physical closeness significantly mediated the olfactory-mortality link for females, even after controlling for social network size. Emotional closeness did not mediate this link. Possible mechanisms underlying this relationship are discussed.