Stress, either physical or psychological, can have a dramatic impact on the immune system. Little progress, however, has been made in understanding stress-induced immune suppression. We report here that mice subjected to chronic 12-hour daily physical restraint for two days significantly increased the expression of Toll-like receptor 4 (TLR4). Interestingly, TLR4-deficient mice are resistant to stress-induced lymphocyte reduction. In addition, restraint stress caused dramatic decrease in T help 1 (Th1) cytokine IFN-γ and IL-2 levels but increase in Th2 cytokine IL-4 in wild type mice. Moreover, the restraint stress significantly inhibits changes of Th1 and Th2 cytokines in TLR4-deficient mice compared with the wild type mice. Therefore, stress modulates the immune system through a TLR4-dependent mechanism.

Depending on the duration and severity, psychological tension and physical stress can enhance or suppress the immune system in both humans and animals. Although it has been established that chronic stress exerts a significant suppressive effect on immune function, the mechanisms by which affects immune responses remain elusive. By employing an in vivo murine system, we revealed that TGF-β1/Smad2/3/Foxp3 axis was remarkably activated following chronic stress. Furthermore, TLR9 and p38 MAPK played a critical role in the activation of TGF-β1/Smad2/3/Foxp3 signaling cascade. Moreover, inhibition of TGF-β1/Smad2/3/Foxp3 or p38 significantly attenuated chronic stress-induced lymphocyte apoptosis and apoptosis-related proteins, as well as the differentiation of T regulatory cells in spleen. Interestingly, disequilibrium of pro-inflammatory and anti-inflammatory cytokines balance caused by chronic stress was also rescued by blocking TGF-β1/Smad2/3/Foxp3 axis. These findings yield insight into a novel mechanism by which chronic stress modulates immune functions and identifies new targets for the development of novel anti-immune suppressant medications.

When humans are faced with multiple options, they must decide whether to choose a novel or less certain option (explore) or stick with what they know (exploit). Exploration is a fundamental cognitive process. Importantly, when humans attempt to solve the explore-exploit dilemma, they must effectively incorporate both feedback and uncertainty to guide their actions. While prior work has shown that both acute (short-term) and chronic (long-term) stress can disrupt how humans solve the explore-exploit dilemma, the mechanisms of how this occurs are unclear. For example, does stress disrupt how people integrate feedback to guide their decisions to explore or exploit, or does stress disrupt computations of uncertainty regarding their choices? Importantly, the use of electroencephalography as a tool can help reveal the impact of stress on explore-exploit decision making by measuring neural signals sensitive to feedback learning and uncertainty. In the present dissertation, I provide evidence from a series of experiments where I examined the impact of both acute and chronic stress on the explore-exploit dilemma while electroencephalographic data was collected. In experiment 1, I exposed participants to an acute stressor and then examined their decisions to switch or stay – as a proxy for explore and exploit decisions – in a multi-arm bandit paradigm. I found tentative evidence that the acute stress response disrupted both the feedback learning signal (the reward positivity) and the uncertainty signal (the switch P300). In experiment 2 I adopted a computational neuroscience approach and directly classified participants decisions as explorations or exploitations using reinforcement learning models. There was only an effect of the acute stress response on feedback signals, in this case, the feedback P300. In experiments 1 and 2, I used contextual bandit tasks where the reward probabilities of the options shifted throughout, and there was no behavioural effect of acute stress on task performance or exploration rate. However, in experiment 3, I examined a learnable bandit where one option was preferred. Again, using computational modelling and electroencephalography, I found tentative evidence that the acute stress response disrupted the feedback learning signals (the feedback P300) and stronger evidence that acute stress disrupted the uncertainty signal (the exploration P300). As well, I observed that the acute stress response reduced task performance and increased exploration rate. Lastly, in experiment 4, I examined the impact of chronic stress exposure on explore-exploit decision making and electrophysiology – while I found no effects of chronic stress, I believe future research is necessary. Taken together, these findings provide novel evidence for the neural mechanisms of how the acute stress response impacts the explore-exploit dilemma through disruptions to feedback learning and assessments of uncertainty. These findings also highlight how theories of the P300 signal may not be properly capturing the varied role of the P300 in cognition. / Graduate

This study explores the influence of chronic stress in college students. It focuses on the broader chronic stressors that college students experience related to physical and mental health, financial health and wellbeing, and presence of social supports, then addresses the more specific chronic stressors related to intersecting identities of race, ethnicity, gender, and sexual orientation. This phenomenon is analyzed under the theoretical frameworks of social determinants of health, intersectionality, and systems theory. An online survey with both open and closed-ended questions was conducted with undergraduate social work students from the Bachelors of Social Work program at the University of Central Florida. The results of the study found that there was links between intersecting identities of participants with higher levels of chronic stress based on their chronic stress scores and participant responses on the influence of their identities on barriers to their physical, mental, and financial health.

Parental psychological control has been found to be associated with both internalized and externalized problems for youth and adolescents. Research contributing to an understanding of the possible antecedents of parental psychological control is both limited and of need; specifically regarding parents' psychological attributes. This study sample included 323 two-parent families and an identified target child from each family. Bowen's theory of family systems, [chronic] stress, and differentiation of self and its relation to parental psychological control was examined. Differentiation of self was hypothesized to mediate the relationship between chronic stress and parental psychological control. Differentiation was conceptualized and measured using two subscales assessing emotional reactivity and emotional cutoff. Fathers and mothers were included in the same model to assess for potential partner influences as well possible gender differences. Parental age, parental education, and family income were also included as control variables. Study analyses included bivariate correlations, independent T-tests, and structural path models; all based on study variables constructed in a structural equation measurement model. To test for mediation by differentiation of self, an initial structural model examining the relationship between levels of parental chronic stress and parental psychological control was utilized. Only paternal chronic stress and paternal education predicted child-reported levels of parental psychological control. Parent-reported levels of differentiation of self, when included in a structural path model, did not mediate the relationship between chronic stress and psychological control but did have a significant indirect effect on this relationship. Both maternal and paternal chronic stress significantly predicted individual parental levels of emotional reactivity and emotional cutoff. Systemically, maternal levels of emotional cutoff predicted paternal levels of parental psychological control and paternal levels of emotional reactivity predicted maternal levels of parental psychological control. No control variables other than paternal education had a salient, significant, or interpretable effect on endogenous study variables (differentiation of self and parental psychological control). Paternal and maternal levels of emotional reactivity appeared to partially mediate the relationship between paternal education and maternal psychological control. Interpretation for results, study limitations and future directions, and clinical implications are discussed.

Variations in anxiety-related behavior are associated with individual allostatic set-points in chronically stressed rats. Actively offensive rats with the externalizing indicators of sniffing and climbing the stimulus and material tearing during 10 days of predator scent stress had reduced plasma corticosterone, increased striatal glutamate metabolites, and increased adrenal 11-dehydrocorticosterone content compared to passively defensive rats with the internalizing indicators of freezing and grooming, as well as to controls without any behavioral changes. These findings suggest that rats that display active offensive activity in response to stress develop anxiety associated with decreased allostatic set-points and increased resistance to stress.

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