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Classic theories of stress and health are largely based on assumptions regarding how different psychosocial stressors influence biological processes that, in turn, affect human health and behavior. Although theoretically rich, this work has yielded little consensus and led to numerous conceptual, measurement, and reproducibility issues. Social Safety Theory aims to address these issues by using the primary goal and regulatory logic of the human brain and immune system as the basis for specifying the social-environmental situations to which these systems should respond most strongly to maximize reproductive success and survival. This analysis gave rise to the integrated, multi-level formulation described herein, which transforms thinking about stress biology and provides a biologically based, evolutionary account for how and why experiences of social safety and social threat are strongly related to health, well-being, aging, and longevity. In doing so, the theory advances a testable framework for investigating the biopsychosocial roots of health disparities as well as how health-relevant biopsychosocial processes crystalize over time and how perceptions of the social environment interact with childhood microbial environment, birth cohort, culture, air pollution, genetics, sleep, diet, personality, and self-harm to affect health. The theory also highlights several interventions for reducing social threat and promoting resilience.

Psychoneuroimmunology and immunopsychiatry are quickly approaching a critical point where the clinical translatability of our promising evidence base will be tested. To maximize our chances for translational success, we believe researchers must adopt causal inference techniques that augment the causal relevance of estimates given theorized causal structures. To illustrate the utility of incorporating causal inference perspectives into psychoneuroimmunological research, we applied the use of directed acyclic graphs and a combination of empirical and simulated data to demonstrate the consequences of controlling for adiposity when testing the hypothesized association between inflammation and depression under the plausible causal structure of increases in adipose tissue leading to increased inflammation that in turn promotes depression. Effect size estimates were pulled from a dataset combining the Midlife in the United States 2 (MIDUS-2) and MIDUS Refresher datasets. Data were extracted and then used to simulate data reflecting an adiposity -> inflammation -> depression causal structure. Next, a Monte Carlo simulation study with 1,000 iterations and three sample size scenarios (N=100, 250, and 500) was conducted testing whether controlling for adiposity when estimating the relation between inflammation and depression influenced the precision of this estimate. Across all three sample size scenarios controlling for adiposity reduced precision of the inflammation depression estimate, highlighting the importance of incorporating causal inference approaches into psychoneuroimmunological research.

Background Digital decision aids are becoming increasingly common in many areas of healthcare. These aids are designed to involve patients in medical decision making, with the aim of improving patient outcomes while decreasing healthcare burden. Previously developed contraceptive-based decision aids have been found to be effective at increasing women’s knowledge about reproductive health and contraception. Here, we sought to evaluate the effectiveness of a novel contraceptive-based decision aid at increasing women’s self-efficacy and knowledge about their reproductive health and contraceptive options, as well as their perceptions of their learning. This study was registered as a clinic trial at ClinicalTrials.gov (Contraception Decision Aid Use and Patient Outcomes, ID# NCT05177783) on 01-05-2022. Methods The Tuune→ contraceptive decision aid’s effectiveness was evaluated by conducting an experiment in which 324 women were assigned to use the TuuneⓇ decision aid or a control decision aid. Primary outcomes included reproductive health self-efficacy, reproductive health and contraceptive knowledge, and perceptions of learning. Secondary analyses examined whether prior experience using hormonal contraceptives moderated the relationship between decision aid and each outcome measure. Results Women assigned to use the Tuune→ decision aid exhibited greater reproductive health self-efficacy, greater knowledge about reproductive health and contraception, and perceived having learned more than women assigned to use the control decision aid. This pattern was also observed in women with previous contraceptive use experience, where women using TuuneⓇ reported better outcomes than women using the control aid, regardless of their history of hormonal contraceptive use experience. Conclusions Use of the Tuune→ contraceptive-based decision aid improved each of the predicted outcomes relative to a control decision aid. This suggests that use of the TuuneⓇ contraceptive-based decision aid is well poised to increase women’s confidence and knowledge about contraceptive use and may also reduce burden on healthcare systems.

Women’s psychological and behavioral responses to hormonal contraceptive (HC)treatment can be highly variable. One of the great challenges to researchers seeking to improve the experiences of women who use HCs is to identify the sources of this variability to minimize unpleasant psychobehavioral side-effects. In the following, we provide recommendations for programs of research aimed at identifying sources of heterogeneity in women’s experiences with HC. First, we review research demonstrating person- and prescription- based heterogeneity in women’s psychobehavioral responses to HCs. Next, we identify several promising person- and prescription- based sources of this heterogeneity that warrant future research. We close with a discussion of research approaches that are particularly well-suited to address the research questions raised in article. Together, this review provides researchers with several promising research pathways to help support the development of a precision medicine approach to HC treatment.

It has long been hypothesized that attractiveness provides a cue to a target's health and immunocompetence. However, much of the research testing this hypothesis has relied on a small number of indirect proxies of immune function, and the results of this research have been mixed. Here, we build on this past research, examining the relationship between target attractiveness and (i) self-reported health, (ii) in vivo measures of inflammation and white blood cell count/composition, and (iii) in vitro tests of targets' immune function, including (c 1 ) leucocyte proliferation in response to immunological stimulants, (c 2 ) phagocytosis of Escherichia coli bioparticles, (c 3 ) NK cell-mediated lysis of target tumour cells, and (c 4 ) Staphylococcus aureus growth in isolated plasma. Results revealed multiple, sometimes sex-differentiated, relationships between targets' immune function and others’ perceptions of their attractiveness. Together, this work suggests complex, often sex-differentiated relationships between immune function, health, and attractiveness.

Much research indicates that exposure to early life adversity (ELA) predicts chronic inflammatory activity, increasing one’s risk of developing diseases of aging later in life. Despite its costs, researchers have proposed that chronic inflammation may be favored in this context because it would help promote immunological vigilance in environments with an elevated risk of infection and injury. Although intuitively appealing, the assumption that exaggerated inflammatory activity predicts favorable immunological outcomes among those exposed to ELA has not been tested. Here, we seek to address this gap, examining the links between exposure to ELA, inflammation, and immune function. Consistent with others’ work, results revealed that those from low socioeconomic status (SES) childhood environments exhibited exaggerated unstimulated inflammatory activity relative to what was observed among those from higher SES childhood environments. Further, results revealed that – although levels of inflammation predicted the magnitude of immunological responses in those from higher SES backgrounds – for those who grew up in low SES environments, higher levels of inflammation were unrelated to the magnitude of immunological responses. Results suggest that exaggerated inflammatory activity in the context of ELA may not predict improved ability to manage acute immunological threats.

Women's psychological and behavioral responses to hormonal contraceptive (HC) treatment can be highly variable. One of the great challenges to researchers seeking to improve the experiences of women who use HCs is to identify the sources of this variability to minimize unpleasant psychobehavioral side-effects. In the following, we provide recommendations for programs of research aimed at identifying sources of heterogeneity in women's experiences with HC. First, we review research demonstrating person- and prescription- based heterogeneity in women's psychobehavioral responses to HCs. Next, we identify several promising person- and prescription- based sources of this heterogeneity that warrant future research. We close with a discussion of research approaches that are particularly well-suited to address the research questions raised in article. Together, this review provides researchers with several promising research pathways to help support the development of a precision medicine approach to HC treatment.

Winter is characterized by stressful conditions which compromise health and render animals more vulnerable to infection and illness than during other times of the year. Organisms are hypothesized to adapt to these seasonal stressors by increasing investment in immune function in response to diminished photoperiod duration. Here, we examined this hypothesis in a sample of healthy human participants. Using several functional immune assays in vitro, as well as by utilizing measures of in vivo proinflammatory cytokine levels, we predicted that shorter day length would be associated with greater investment in immunological function. Results revealed that shorter days predicted significant upregulation of several facets of immune function, including natural killer cell cytotoxicity, peripheral blood mononuclear cell proliferation (in response to, and in the absence of stimulation), and plasma levels of interleukin-6, as well as lower rates of Staphylococcus aureus growth in serum ex vivo. Further, consistent with the hypothesis that these trade-offs would be offset by decreased investment in mating effort, shorter day length also predicted lower levels of total testosterone in men. These results suggest that ambient photoperiod may be a powerful regulator of human immunological activity, providing some of the first evidence of seasonal changes in multiple facets of human immune function.

Early life stress increases one’s risk for health problems later in life, and many studies find that these effects are sex-differentiated. Here, we examined relationships between multiple sources of early life stress and adult immune function in humans across several functional assays. Adult participants provided retrospective information about their childhood (a) socioeconomic status, (b) household unpredictability, and (c) exposure to adverse experiences. Participants’ peripheral blood mononuclear cells (PBMCs) were then isolated for use in functional assays of immune performance: (a) tumor cell lysis by natural killer cells, (b) phagocytosis of Escherichia coli bioparticles, and (c) mitogen-induced leukocyte proliferation and cytokine release. In men, lower childhood socioeconomic status predicted decrements in immunological performance across functional assays, along with greater spontaneous cytokine release from PBMCs. These changes co-occurred with elevations in plasma testosterone levels. Similar effects were not observed for other sources of stress, nor were they found in women (with the exception of spontaneous cytokine release). These findings provide evidence that low childhood socioeconomic status has a lasting negative impact on multiple aspects of immune function, particularly in men.

Decades of research finds associations between personality traits and health. In recent years, it has become clear that the activities of the immune system play a key role in linking these variables. In the current work, we add to this research by exploring the relationship between Big Five personality traits and (Study 1) polymorphisms known to impact cytokine release and (Study 2) immunological parameters measured in vivo (differential white blood cell counts, plasma proinflammatory cytokine levels) and in vitro (proinflammatory cytokine release by peripheral blood mononuclear cells, Staphylococcus aureus growth in plasma). Results provide insights into potential mechanistic drivers of the link between personality and immune function and the possibility that, in some cases, relationships between personality and immune function may be sex differentiated.

Here, we examine the impact of one's willingness to try new foods on others' perceptions of sexual unrestrictedness and desirability as a sexual and romantic partner. Guided by insights from past research, we hypothesized that targets who are willing to try new foods would be perceived as being more desirable sexual and romantic partners (Study 1) and as being less sexually restricted (Studies 2–4) than targets who are unwilling to try new foods. Results supported this hypothesis and further indicated that this pattern is specific to willingness to try new foods, not general willingness to try new things (Study 3). Additionally, results revealed that the relationship between willingness to try new food and inferences of sexual unrestrictedness is driven by perceptions of target's relatively lower levels of sexual disgust sensitivity and not by the belief that the target is in better health or has superior immune function (Study 4). Together, these results suggest that people's willingness to try new foods may impact how they are perceived by prospective dates and mates.

Although the criminal justice system is designed around the idea that individuals are invariant in their responses to punishment, research indicates that individuals exhibit a tremendous amount of variability in their punishment sensitivity. This raises the question of why; what are the individual- and situation-level variables that impact a person's sensitivity to punishment? In the current research, we synthesize theory and research on inflammation, learning, and evolutionary biology to examine the relationship between inflammatory activity and sensitivity to punishment. These theories combine to predict that inflammatory activity - which is metabolically costly and reflects a context in which the net payoff associated with future oriented behaviors is diminished - will decrease sensitivity to punishment, but not rewards. Consistent with this hypothesis, Study 1 found that in U.S. states with a higher infectious disease burden (a proxy for average levels of inflammatory activity) exhibit harsher sentencing in their criminal justice systems. Studies 2 and 3 experimentally manipulated variables known to impact bodily inflammatory activity and measured subsequent punishment and reward sensitivity using a probabilistic selection task. Results revealed that (a) increasing inflammation (i.e., completing the study in a dirty vs. clean room) diminished punishment sensitivity (Study 2), whereby (b) administering a non-steroidal anti-inflammatory drug, suppressing inflammatory activity, enhanced it. No such changes were found for reward sensitivity. Together, these results provide evidence of a link between the activities of the immune system and punishment sensitivity, which may have implications for criminal justice outcomes.

Much research finds that early life socioeconomic disadvantage predicts poorer health later in life, even among those whose conditions improve in adulthood. Although there are numerous factors that contribute to this association, recent research suggests that growing up in adverse socioecological environments may promote developmental patterns that facilitate pre-reproductive survival in harsh environments, but can also come at the cost of reduced longevity. Here, we review recent research demonstrating that early life exposure to low socioeconomic status can become embedded in the mechanisms that regulate (a) bodily inflammatory activity and (b) energy regulation in ways that contribute to poor health. This research offers new insights into ways that early life environments can get under one’s skin to impact health and longevity.

A growing body of research indicates that one's early life experiences may play an important role in regulating patterns of energy intake in adulthood. In particular, adults who grew up under conditions characterized by low socioeconomic status (SES) tend to eat in the absence of hunger (EAH), a pattern that is not generally observed among higher-SES individuals. In the current study, we sought to examine (a) the environmental correlates of low SES that drive the association between low childhood SES and EAH and (b) whether the relationship between these variables is already manifest in children ages 3-14. Results of our study revealed that growing up in low-SES environments predicted less food security, diminished ability to meet financial needs, and less environmental predictability/safety. Further, the results indicated that reduced environmental predictability/safety in the children's environment interacted with children's current energy need to predict eating behavior. Consistent with patterns observed in adults, children from more predictable/safe environments ate food commensurate with their energy need, whereas those from less predictable/safe environments ate comparably high amounts of food across levels of energy need. These results offer needed insights into the development of environmentally-contingent energy-regulation strategies.

A growing body of research suggests that hormonal contraceptive (HC) use may be associated with lower self-control, as well as structural and functional differences in women's brains that could contribute to differences in perseverance on tasks requiring cognitive control. Here, we sought to extend this research by examining the relationship between HC use and college-aged women's perseverance (i.e., time spent) and performance on tasks requiring cognitive control. Across two studies, we find that, compared to naturally-cycling women, women using HCs display less perseverance on both simple (i.e., a spot-the-difference game) and challenging (i.e., Graduate Record Examination quantitative problems) tasks. Moreover, these differences in perseverance were found to predict performance decrements across tasks, with women taking HCs performing worse because they spent less time on the tasks. By demonstrating how HC use may influence perseverance and thereby performance, these results contribute to a growing body of research examining the unintended implications of HC use on cognition, learning, and memory.