The Impact of a Digital Contraceptive Decision Aid on User Outcomes: Results of an Experimental, Clinical Trial.

BACKGROUND: Nearly 40% of unplanned pregnancies in the USA are the result of inconsistent or incorrect contraceptive use. Finding ways to increase women's comfort and satisfaction with contraceptive use is therefore critical to public health. One promising pathway for improving patient outcomes is through the use of digital decision aids that assist women and their physicians in choosing a contraceptive option that women are comfortable with. Testing the ability of these aids to improve patient outcomes is therefore a necessary first step toward incorporating this technology into traditional physician appointments. PURPOSE: To evaluate the effectiveness of a novel contraceptive decision aid at minimizing decisional conflict and increasing comfort with contraception among adult women. METHODS: In total, 310 adult women were assigned to use either the Tuune contraceptive decision aid or a control aid modeled after a leading online contraceptive prescriber's patient intake form. Participants then completed self-report measures of decisional conflict, contraceptive expectations, satisfaction, and contraceptive use intentions. Individual between-subjects analysis of variance (ANOVA) models were used to examine these outcomes. RESULTS: Women using the Tuune decision aid (vs. those using the control aid) reported lower decisional conflict, more positive contraceptive expectations, greater satisfaction with the decision aid and recommendation, and more positive contraceptive use intentions. CONCLUSIONS: Use of Tuune improved each of the predicted patient outcomes relative to a control decision aid. Online decision aids, particularly when used alongside physician consultations, may be an effective tool for increasing comfort with contraceptive use. CLINICAL TRIALS REGISTRATION #: NCT05177783, ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT05177783.

Digital decision aids that help women and their physicians choose contraceptive options that women are most comfortable with present one promising way to improve contraceptive use outcomes, such as avoiding unplanned pregnancies. However, current decision aids have been found to struggle in helping improve women's satisfaction with and confidence in their contraceptive choices. The aim of this study was to test the effectiveness of a new digital decision aid, named Tuune, at helping improve women's confidence and comfort with contraception. Three hundred and ten adult women were randomly assigned to use and then receive a contraceptive recommendation from either the Tuune decision aid or a control aid designed after leading traditional health intake forms. Women's confidence and satisfaction with the aids, as well as their contraceptive recommendation, were then compared between groups. We found good evidence to suggest that women using the Tuune contraceptive decision aid were more satisfied and positive about their contraceptive choices and reported greater intentions to use contraception with increased confidence compared to women who used the control decision aid. New online decision aids, like Tuune, may be an effective tool for increasing women's comfort and experiences using contraception.

Longitudinal associations between women's cycle characteristics and sexual motivation using Flo cycle tracking data.

In the current research, we used data from a sample of 16,327 menstrual cycle tracking app users to examine the association between menstrual cycle characteristics and sexual motivation tracked over 10 months of app use. Guided by past work that finds links between menstrual cycle characteristics related to conception risk and sexual motivation, we found that (a) between-women, shorter (r = - 0.04, p = 0.007), more regular cycles predicted small increases in sexual motivation (r = - 0.04, p = 0.001); (b) within-women, shorter cycles predicted greater sexual motivation that month (r = - 0.04, p < 0.001) and (c) the next month (ßs: - 0.10 to - 0.06, ps < 0.001), but (d) changes in sexual motivation did not reliably precede changes in cycle length (ßs: - 0.01 to 0.02, ps > 0.15). Within-woman analyses also revealed that (e) shorter cycles were followed by more frequent reports of fatigue (ß = - 0.06, p < 0.001), insomnia (ß = - 0.03, p < 0.001), and food cravings (ß = - 0.04, p < 0.001). Together, results suggest that menstrual cycles characteristics and sexual motivation may covary together in ways that reflect changing investments in reproduction. Small effect sizes and lack of experimental control warrant cautious interpretations of results.

Human immune and metabolic biomarker levels, and stress-biomarker associations, differ by season: Implications for biomedical health research.

Although seasonal changes in physiology are well documented, little is known about how human immune and metabolic markers vary across seasons, and no studies have examined how stress → health biomarker associations differ across the year. To investigate these issues, we analyzed data from 2118 participants of the Midlife in the United States (MIDUS) study to determine whether there were differences in (a) levels of 19 immune and metabolic markers, and (b) the association between perceived stress and each biomarker across the year. Results of component-wide boosted generalized additive models revealed seasonal patterning for most biomarkers, with immune proteins generally peaking when days were shorter. Moreover, whereas levels of hemoglobin A1C rose from late fall to spring, triglycerides were elevated in the summer and fall, and high-density lipoprotein decreased steadily from January to December. Urinary cortisol and cortisone exhibited opposite patterns, peaking at the beginning and end of the year, respectively. Most critically, we found that the effects of perceived stress on 18 of the 19 health biomarkers assessed varied by month of measurement. In some cases, these differences involved the magnitude of the stress → biomarker association but, in other cases, it was the direction of the effect that changed. Studies that do not account for month of biomarker assessment may thus yield misleading or unreproducible results.

The Stress Phenotyping Framework: A multidisciplinary biobehavioral approach for assessing and therapeutically targeting maladaptive stress physiology.

Although dysregulated stress biology is becoming increasingly recognized as a key driver of lifelong disparities in chronic disease, we presently have no validated biomarkers of toxic stress physiology; no biological, behavioral, or cognitive treatments specifically focused on normalizing toxic stress processes; and no agreed-upon guidelines for treating stress in the clinic or evaluating the efficacy of interventions that seek to reduce toxic stress and improve human functioning. We address these critical issues by (a) systematically describing key systems and mechanisms that are dysregulated by stress; (b) summarizing indicators, biomarkers, and instruments for assessing stress response systems; and (c) highlighting therapeutic approaches that can be used to normalize stress-related biopsychosocial functioning. We also present a novel multidisciplinary Stress Phenotyping Framework that can bring stress researchers and clinicians one step closer to realizing the goal of using precision medicine-based approaches to prevent and treat stress-associated health problems.

Longitudinal changes in sexual desire and attraction among women who started using the Natural Cycles app.

Many women experience sexual side effects, such as decreased libido, when taking hormonal contraceptives (HCs). However, little is known about the extent to which libido recovers after discontinuing HCs, nor about the timeframe in which recovery is expected to occur. Given that HCs suppress the activities of multiple endogenous hormones that regulate both the ovulatory cycle and women's sexual function, resumption of cycles should predict libido recovery. Here, using a combination of repeated and retrospective measures, we examined changes in sexual desire and partner attraction (among partnered women) across a three-month period in a sample of Natural Cycles users (Survey 1: n = 1596; Survey 2: n = 550) who recently discontinued HCs. We also tested whether changes in these outcomes coincided with resumption of the ovulatory cycle and whether they were associated with additional factors related to HC use (e.g., duration of HC use) or relationship characteristics (e.g., relationship length). Results revealed that both sexual desire and partner attraction, on average, increased across three months after beginning to use Natural Cycles. While the prediction that changes in sexual desire would co-occur with cycle resumption was supported, there was also evidence that libido continued to increase even after cycles resumed. Together, these results offer new insights into relationships between HC discontinuation and women's sexual psychology and lay the groundwork for future research exploring the mechanisms underlying these effects.

Sex Differences in Stress Susceptibility as a Key Mechanism Underlying Depression Risk.

PURPOSE OF REVIEW: Although females are at relatively greater risk for a variety of disorders, including depression, the biological mechanisms underlying this striking health disparity remain unclear. To address this issue, we highlight sex differences in stress susceptibility as a key mechanism potentially driving this effect and describe the interacting inflammatory, hormonal, epigenomic, and social-environmental mechanisms involved. RECENT FINDINGS: Using the Social Signal Transduction Theory of Depression as a theoretical framework, women's elevated risk for depression may stem from a tight link between life stress, inflammation, and depression in women. Further, research finds hormonal contraceptive use alters cortisol and inflammatory reactivity to acute stress in ways that may increase depression risk in females. Finally, beyond established epigenetic mechanisms, mothers may transfer risk for depression to their female offspring through stressful family environments, which influence stress generation and stress-related gene expression. Together, these findings provide initial, biologically plausible clues that may help explain the relatively greater risk for depression in females vs. males. Looking forward, much more research is needed to address the longstanding underrepresentation of females in biomedical research on the biology of stress and depression.

Multi-omics in stress and health research: study designs that will drive the field forward.

Despite decades of stress research, there still exist substantial gaps in our understanding of how social, environmental, and biological factors interact and combine with developmental stressor exposures, cognitive appraisals of stressors, and psychosocial coping processes to shape individuals' stress reactivity, health, and disease risk. Relatively new biological profiling approaches, called multi-omics, are helping address these issues by enabling researchers to quantify thousands of molecules from a single blood or tissue sample, thus providing a panoramic snapshot of the molecular processes occurring in an organism from a systems perspective. In this review, we summarize two types of research designs for which multi-omics approaches are best suited, and describe how these approaches can help advance our understanding of stress processes and the development, prevention, and treatment of stress-related pathologies. We first discuss incorporating multi-omics approaches into theory-rich, intensive longitudinal study designs to characterize, in high-resolution, the transition to stress-related multisystem dysfunction and disease throughout development. Next, we discuss how multi-omics approaches should be incorporated into intervention research to better understand the transition from stress-related dysfunction back to health, which can help inform novel precision medicine approaches to managing stress and fostering biopsychosocial resilience. Throughout, we provide concrete recommendations for types of studies that will help advance stress research, and translate multi-omics data into better health and health care.

Hormonal contraceptive use is associated with differences in women's inflammatory and psychological reactivity to an acute social stressor.

Women using hormonal contraceptives (HCs) exhibit numerous signs of chronic inflammation, including elevated C-reactive protein levels and greater risk of developing mood and autoimmune disorders. However, users and non-users of HCs often have similar circulating proinflammatory cytokine levels, making the mechanism of association unclear. One possible explanation for this paradox is that HC users exhibit differences in their inflammatory responses to psychosocial stress that, over time, could contribute to chronic inflammation and its pathologies. Here, we tested this possibility by examining women's glucocorticoid, inflammatory, and psychological responses to the Trier Social Stress Test (TSST) in 67 naturally cycling (NC) and 60 oral HC-using women (Mage = 19.31, SDage = 1.95). As hypothesized, HC users and NC women exhibited different glucocorticoid and proinflammatory cytokine responses to the TSST. For NC women, TSST-induced increases in glucocorticoids were uncommon, and increases in glucocorticoids were accompanied by elevations in IL-6. In contrast, for women using HCs, increases in glucocorticoids in response to the TSST were common, and increases in glucocorticoids were accompanied by increases in TNF-α. HC users and NC women also differed in their psychological responses to the TSST, with HC users reporting elevated stress levels compared to NC women. Together, these results suggest that HC use impacts women's glucocorticoid, inflammatory, and psychological responses to psychosocial stress, potentially contributing to observed differences in these women's mental and physical health.

Multi-omics approaches in psychoneuroimmunology and health research: Conceptual considerations and methodological recommendations.

The field of psychoneuroimmunology (PNI) has grown substantially in both relevance and prominence over the past 40 years. Notwithstanding its impressive trajectory, a majority of PNI studies are still based on a relatively small number of analytes. To advance this work, we suggest that PNI, and health research in general, can benefit greatly from adopting a multi-omics approach, which involves integrating data across multiple biological levels (e.g., the genome, proteome, transcriptome, metabolome, lipidome, and microbiome/metagenome) to more comprehensively profile biological functions and relate these profiles to clinical and behavioral outcomes. To assist investigators in this endeavor, we provide an overview of multi-omics research, highlight recent landmark multi-omics studies investigating human health and disease risk, and discuss how multi-omics can be applied to better elucidate links between psychological, nervous system, and immune system activity. In doing so, we describe how to design high-quality multi-omics studies, decide which biological samples (e.g., blood, stool, urine, saliva, solid tissue) are most relevant, incorporate behavioral and wearable sensing data into multi-omics research, and understand key data quality, integration, analysis, and interpretation issues. PNI researchers are addressing some of the most interesting and important questions at the intersection of psychology, neuroscience, and immunology. Applying a multi-omics approach to this work will greatly expand the horizon of what is possible in PNI and has the potential to revolutionize our understanding of mind-body medicine.

Incorporating causal inference perspectives into psychoneuroimmunology: A simulation study highlighting concerns about controlling for adiposity in immunopsychiatry.

Psychoneuroimmunology and immunopsychiatry are quickly approaching a critical point where the clinical translatability of their evidence base will be tested. To maximize 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 psychoneuroimmunology, we applied directed acyclic graphs and a combination of empirical and simulated data to demonstrate the consequences of controlling for adiposity when testing the association between inflammation and depression under the plausible causal structure of increases in adipose tissue leading to greater 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 used to simulate data reflecting an adiposity â†’ inflammation â†’ depression causal structure. Next, a Monte Carlo simulation study with 1,000 iterations and three sample size scenarios (Ns = 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 simulation scenarios, controlling for adiposity reduced precision of the inflammation â†’ depression estimate, suggesting that researchers primarily interested in quantifying inflammation â†’ depression associations should not control for adiposity. This work thus underscores the importance of incorporating causal inference approaches into psychoneuroimmunological research.

Human social genomics: Concepts, mechanisms, and implications for health.

The exciting field of human social genomics provides an evolutionarily informed, multilevel framework for understanding how positive and negative social-environmental experiences affect the genome to impact lifelong health, well-being, behavior, and longevity. In this review, we first summarize common patterns of socially influenced changes in the expression of pro-inflammatory and antiviral immune response genes (e.g., the Conserved Transcriptional Response to Adversity), and the multilevel psychological, neural, and cell signaling pathways by which social factors regulate human gene expression. Second, we examine how these effects are moderated by genetic polymorphisms and the specific types of social-environmental experiences that most strongly affect gene expression and health. Third, we identify positive psychosocial experiences and interventions that have been found to impact gene expression. Finally, we discuss promising opportunities for future research on this topic and how health care providers can use this information to improve patient health and well-being.

Social Safety Theory: Conceptual foundation, underlying mechanisms, and future directions.

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.

Moving beyond the mean: Promising research pathways to support a precision medicine approach to hormonal contraception.

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.

Using Ecological Momentary Assessments to Study How Daily Fluctuations in Psychological States Impact Stress, Well-Being, and Health.

Despite great interest in how dynamic fluctuations in psychological states such as mood, social safety, energy, present-focused attention, and burnout impact stress, well-being, and health, most studies examining these constructs use retrospective assessments with relatively long time-lags. Here, we discuss how ecological momentary assessments (EMAs) address methodological issues associated with retrospective reports to help reveal dynamic associations between psychological states at small timescales that are often missed in stress and health research. In addition to helping researchers characterize daily and within-day fluctuations and temporal dynamics between different health-relevant processes, EMAs can elucidate mechanisms through which interventions reduce stress and enhance well-being. EMAs can also be used to identify changes that precede critical health events, which can in turn be used to deliver ecological momentary interventions, or just-in-time interventions, to help prevent such events from occurring. To enable this work, we provide examples of scales and single-item questions used in EMA studies, recommend study designs and statistical approaches that capitalize on EMA data, and discuss limitations of EMA methods. In doing so, we aim to demonstrate how, when used carefully, EMA methods are well poised to greatly advance our understanding of how intrapersonal dynamics affect stress levels, well-being, and human health.

Early life adversity, inflammation, and immune function: An initial test of adaptive response models of immunological programming.

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.

More than just a pretty face? The relationship between immune function and perceived facial attractiveness.

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 (c1) leucocyte proliferation in response to immunological stimulants, (c2) phagocytosis of Escherichia coli bioparticles, (c3) NK cell-mediated lysis of target tumour cells, and (c4) 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.

Exploring the Links between Personality and Immune Function.

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.

Sex differences in the impact of childhood socioeconomic status on 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.

Does the Punishment Fit the Crime (and Immune System)? A Potential Role for the Immune System in Regulating Punishment Sensitivity.

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.

Low socioeconomic status and eating in the absence of hunger in children aged 3-14.

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.