S. For example, the past studies by Gianaros et al. (2008) and Muscatell et al. (2012) both examined how status influenced amygdala reactivity to external images of threatening facial expressions that were largely context-free, whereas in this study we created a more personal threat experience by using an elaborate cover story that provided context for the evaluative words. Given that the amygdala is hypothesized to be X-396 manufacturer important for the detection of emotion and salience in the environment, but not sufficient for the generation of emotional `feelings’ (Wager et al., 2008), it is possible that the use of an emotion-generation task (compared to an emotion-detection task) contributed to the differences in findings between the present investigation and past work in this area. Another possibility is that threatening faces may be more salient than written words, and thus may lead to greater amygdala activation (Adolphs, 2010; Cunningham and Brosch, 2012). Much more research is needed to fully specify the precise neural underpinnings of reactivity to different types of social threats, and how social status may affect these responses. The present finding that social status is related to inflammatory responses to stress replicates two prior studies showingthat individuals lower in subjective social status have a greater stressor-evoked increase in IL-6 (Brydon et al., 2004; Derry et al., 2013). Importantly, while the stress tasks used in these previous experiments involved both cognitive effort and some degree of social evaluation, the stressor used in this study isolated the social evaluative component. Therefore, it appears that the effects of status on inflammatory responses to stress are not simply due to performing a cognitively demanding task on which lower status individuals may perform more poorly (Noble et al., 2007). Rather, it may be that the social-evaluative component of the previously used stress tasks drives the observed increases in inflammation, as lower-status individuals are more sensitive to social cues in the environment (Kraus and Keltner, 2009) and may thus be especially sensitive to the effects of social stress. Future studies could directly test this possibility by assigning participants to complete either a social or a cognitive stressor and examining how social status influences inflammatory responses to these two different tasks. It should also be noted that in this study, social status was associated with stressor-evoked increases in IL-6, but not TNFa, another pro-inflammatory cytokine often studied in the context of stress research (Steptoe et al., 2007). It is possible that a restricted range or floor effect in TNF-a responses may have limited our ability to detect associations between social status and this inflammatory marker, as the overall group did not show changes in TNF-a after exposure to the stressor (Muscatell et al., 2015). It will be important for future studies to clarify the potential specificity in the relation between social status and measures of inflammatory activity. Interestingly, while the neural and inflammatory data suggest that individuals reporting lower status may be more reactive to a social stressor, a very different pattern Chaetocin site emerged when examining how social status was related to affective responses to the stressor. Specifically, higher subjective status individuals reported greater increases in negative feelings from pre- to poststress, compared with lower subjective status individuals.S. For example, the past studies by Gianaros et al. (2008) and Muscatell et al. (2012) both examined how status influenced amygdala reactivity to external images of threatening facial expressions that were largely context-free, whereas in this study we created a more personal threat experience by using an elaborate cover story that provided context for the evaluative words. Given that the amygdala is hypothesized to be important for the detection of emotion and salience in the environment, but not sufficient for the generation of emotional `feelings’ (Wager et al., 2008), it is possible that the use of an emotion-generation task (compared to an emotion-detection task) contributed to the differences in findings between the present investigation and past work in this area. Another possibility is that threatening faces may be more salient than written words, and thus may lead to greater amygdala activation (Adolphs, 2010; Cunningham and Brosch, 2012). Much more research is needed to fully specify the precise neural underpinnings of reactivity to different types of social threats, and how social status may affect these responses. The present finding that social status is related to inflammatory responses to stress replicates two prior studies showingthat individuals lower in subjective social status have a greater stressor-evoked increase in IL-6 (Brydon et al., 2004; Derry et al., 2013). Importantly, while the stress tasks used in these previous experiments involved both cognitive effort and some degree of social evaluation, the stressor used in this study isolated the social evaluative component. Therefore, it appears that the effects of status on inflammatory responses to stress are not simply due to performing a cognitively demanding task on which lower status individuals may perform more poorly (Noble et al., 2007). Rather, it may be that the social-evaluative component of the previously used stress tasks drives the observed increases in inflammation, as lower-status individuals are more sensitive to social cues in the environment (Kraus and Keltner, 2009) and may thus be especially sensitive to the effects of social stress. Future studies could directly test this possibility by assigning participants to complete either a social or a cognitive stressor and examining how social status influences inflammatory responses to these two different tasks. It should also be noted that in this study, social status was associated with stressor-evoked increases in IL-6, but not TNFa, another pro-inflammatory cytokine often studied in the context of stress research (Steptoe et al., 2007). It is possible that a restricted range or floor effect in TNF-a responses may have limited our ability to detect associations between social status and this inflammatory marker, as the overall group did not show changes in TNF-a after exposure to the stressor (Muscatell et al., 2015). It will be important for future studies to clarify the potential specificity in the relation between social status and measures of inflammatory activity. Interestingly, while the neural and inflammatory data suggest that individuals reporting lower status may be more reactive to a social stressor, a very different pattern emerged when examining how social status was related to affective responses to the stressor. Specifically, higher subjective status individuals reported greater increases in negative feelings from pre- to poststress, compared with lower subjective status individuals.
