The effects of childhood adversity on twenty-five disease biomarkers and twenty health conditions in adulthood: Differences by sex and stressor type.

BACKGROUND: Although early adversity is now recognized as a major public health concern, it remains unclear if the effects of early-life stressors on disease biology and health differ by sex or stressor type. Because childhood stressors often covary, examining whether such stressors typically occur together (e.g., cumulative adversity) or in distinct multivariate patterns is needed to determine if and how different life stressors uniquely affect disease biology and health. METHOD: To investigate, we conducted latent class analyses (LCA) to identify clusters of adults experiencing multiple childhood stressors (N=2,111, Mage = 53.04, 54.8 % female) in the Midlife in the United States (MIDUS) Study. We then tested how latent stressor exposure groups, and individual stressors, related to 25 biomarkers of inflammation, metabolism, and stress, and 20 major health conditions. Multivariate effect sizes were estimated using Mahalanobis's D. RESULTS: Optimal LCA models yielded three female (Low-, Moderate-, and High-Stress) and two male (Low- and High-Stress) stressor exposure classes. The High-Stress classes had greater inflammation (male: D=0.43; female: D=0.59) and poorer metabolic health (male: D=0.32-0.33; female: D=0.32-0.47). They also had more cardiovascular (male: HR=1.56 [1.17, 2.07]; female: HR=1.97 [1.50, 2.58]), cancer (male: HR=2.41 [1.52, 3.84]; female: HR=2.51 [1.45, 4.35]), metabolic (male: HR=1.54 [1.16, 2.03]; female: HR=2.01 [1.43, 2.83]), thyroid (male: HR=3.65 [1.87, 7.12]; female: HR=2.25 [1.36, 3.74]), arthritis (male: HR=1.81 [1.30, 2.54]; female: HR=1.97 [1.41, 2.74]), and mental/behavioral health problems (male: HR=2.62 [1.90, 3.62]; female; HR=3.67 [2.72, 4.94]). Moreover, stressors were related to these outcomes in a sex- and stressor-specific manner. CONCLUSIONS: Childhood adversity portends worse biological health and elevated risk for many major health problems in a sex- and stressor-specific manner. These findings advance stress theory and may help inform precision interventions for managing stress.

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 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.

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.

Exploring links between pathogen avoidance motivation, COVID-19 case counts, and immune function.

OBJECTIVES: The selection pressures exerted by pathogens have played important roles in shaping the biology and behavior of animals, including humans. Immune systems recognize and respond to cues of infection or damage by coordinating cellular, humoral, and metabolic shifts that promote recovery. Moreover, animals also possess a repertoire of behavioral tools to help combat the threat of pathogens, often referred to as the behavioral immune system. Recently, researchers have begun to examine how cognitive, affective, and behavioral disease avoidance mechanisms interact with the biological immune system. METHODS: The present study explored relationships among individual differences in behavioral immune system activity (e.g., pathogen disgust), shifts in SARS-CoV-2 infection risk (i.e., 7-day case averages), and immune function in a community cohort from McLennan County, Texas, USA (n = 387). RESULTS: Levels of disease concern were not consistently associated with immune markers. However, serum levels of IFN-γ, TNF-α, IL-2, and IL-8, as well as serum killing ability of Escherichia coli, each varied with case counts. Additional analyses found that case counts also predicted changes in stress physiology, but not subjective measures of distress. However, follow-up mediation models did not provide evidence that relationships between case counts and immunological outcomes were mediated through levels of stress. CONCLUSIONS: The present project provides initial evidence that markers of immune function may be sensitive to changes in infection risk during the COVID-19 pandemic. This adds to the growing body of research finding relationships among behavioral and biological pathogen management mechanisms.

Waco COVID Survey: A Community-Based SARS-CoV-2 Serological Surveillance Study in Central Texas.

In early-2020, the epidemiology of the SARS-CoV-2 virus was still in discovery and initial reports about the role of asymptomatic individuals were developing. The Waco COVID Survey was implemented in mid-2020 with targeted serological surveillance to assess relationships among risk factors and asymptomatic transmission in McLennan County, Texas, USA. Because large-scale random sampling of the population was not feasible, a targeted and repeated sampling of specific clustered groups of asymptomatic individuals was employed. This included four waves (initial intake [n = 495], two follow-ups separated by a month [n = 348; n = 287], and a final follow-up one year later [n = 313]) of sampling participants in different risk categories: (a) healthcare workers (e.g., physicians, nurses, etc.) and first responders, (b) essential service employees (e.g., convenience and grocery stores, restaurants focused on delivery and carry-out), (c) employees whose businesses began reopening on May 1 (e.g., dine-in restaurants, churches, etc.) including church attendees, and (d) individuals that practiced intensive isolation. The survey collected information on demographics, compliance with public health recommendations, satisfaction with government responses, health history, attitudes regarding the SARS-CoV-2 virus and COVID-19 disease, health behaviors, personality, stress, and general affect. Results illustrate pandemic fatigue over time, the influence of political leniency on opinions and behaviors, the importance of face coverings in preventing infection, and the positive impact of vaccination in the community. This project remains one of the largest longitudinal SARS-CoV-2 antibody seroprevalence surveys in the US, and details for successful implementation and community involvement are discussed.

Dynamics of temperature change during experimental respiratory virus challenge: Relationships with symptoms, stress hormones, and inflammation.

Thermoregulation is a complex, dynamic process involving coordination between multiple autonomic, endocrine, and behavioral mechanisms. In the context of infection, this intricate machinery generates fever, a process believed to serve vital functions in the body's defense against pathogens. In addition to increasing core temperature, infection can lead to changes in the dynamic fluctuations in body temperature over time. The patterns of these deviations may convey information about the health of the body and the course of illness. Here, we utilized dynamic structural equation modeling to explore patterns of body temperature change following an experimental respiratory virus challenge in an aggregated, archival dataset of human participants (N = 1,412). We also examined whether temperature dynamics during infection were related to symptom severity, as well as individual differences in biomarkers of inflammation and stress. We found that individuals meeting the criteria for infection exhibited higher but less stable body temperatures over time compared to those not meeting criteria of infection. While temperature parameters did not reliably predict symptom severity, higher levels of nasal proinflammatory cytokines were associated with lower, more consistent temperatures during the study period. Further, levels of salivary cortisol and urinary catecholamines measured at the beginning of the study appeared to have disparate effects on temperature change. In sum, this research highlights the utility of dynamic time series modeling as a framework for studying body temperature change and lends novel insights into how stress may interact with infection to influence patterns of thermoregulation.

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.

Travel medicine meets conservation medicine in St. Kitts: Disinhibition, cognitive-affective inconsistency, and disease risk among vacationers around green monkeys (Chlorocebus sabaeus).

Despite concern about environmental protection, travelers often underestimate the contribution they may have to disease transmission to other species, as well as the risk of becoming infected themselves. Tourists in general tend to accept more physical risks when traveling than when at home, and much of this can be blamed on the temporary loss of situational awareness and loss of inhibition with a corresponding relaxed attitude toward safety. To better understand environmental attitudes and travel health knowledge and behaviors, a detailed survey of adult tourists was distributed on the island of St. Kitts, home to many green monkeys. Data from 1097 respondents were collected at two locations where cruise ship passengers typically visit the island. Results revealed that even though individuals with more positive environmental attitudes were more willing to take steps to mitigate tourism-related disease transmission, they were also more likely to report wanting to touch or feed a monkey/ape. Similarly, those more willing to prevent the spread of diseases (e.g., wear a mask and report any illnesses to park authorities) were actually more likely to want to touch or feed a monkey/ape. The human desire for physical contact with other species may be partly the result of biophilia, emotionally arousing events (like contact with exotic species) that can lead to further disinhibition, and social media platforms that provide opportunities for exhibitionism. The attitude-behavior incongruency identified here may also be explained through cognitive-affective inconsistency: environmentally-oriented individuals believe that it is prudent to take steps to prevent zoonotic disease transmission but also desire to touch or feed exotic species as it may be emotionally rewarding. Individuals for whom physically interacting with monkeys/apes may be emotionally rewarding may not alter their behavior in response to cognitive means of persuasion; techniques aimed at appealing to emotions may be more effective.

Predictability or controllability: Which matters more for the BCD?

Pepper & Nettle's theory of the behavioral constellation of deprivation (BCD) would benefit from teasing apart the conceptually distinct - although related - constructs of predictability and control. Our commentary draws from prior research conducted in the learning domain to demonstrate that predictability moderates the effects of control and independently exerts a powerful influence on outcomes relevant to the BCD.

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.

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.

Survey of COVID-19 isolation cases at a major university campus in the United States.

Objective: Baylor University established a surveillance system to assess the needs of students and faculty in isolation from SARS-CoV-2 as well as any longer-term symptoms. Participants: Overall, there were 309 responses between March 20 and May 19, 2021. Methods: A survey covering experience in isolation, symptoms, vaccination, and demographic characteristics was emailed to individuals on Day 7 of isolation; a follow-up health survey was sent 30 days later. Results: Only 9.6% of respondents reported needing assistance while in isolation. Nearly 75% of respondents experienced COVID-19 symptoms in isolation, and 31.9% had remaining symptoms after isolation. Older age, being male, and more severe symptoms were associated with longer symptom duration. Those vaccinated had lower odds of developing symptoms and having symptoms remaining post-isolation. Conclusions: The present study adds to our understanding of long-COVID in young adult populations, while providing a framework for similar institutions to sustain operations during a global pandemic.

Lower testosterone levels are associated with higher risk of death in men.

Background and Objectives: Testosterone plays an important role in regulating male development, reproduction and health. Declining levels across the lifespan may reflect, or even contribute to, chronic disease and mortality in men. Methodology: Relationships between testosterone levels and male mortality were analyzed using data from multiple samples of the cross-sectional National Health and Nutrition Examination Survey (n = 10 225). Target outcomes included known deaths from heart disease, malignant neoplasms, chronic lower respiratory diseases, cerebrovascular diseases, Alzheimer's disease, diabetes mellitus, influenza and pneumonia, kidney diseases, and accidents or unintentional injuries. Results: Results of discrete-time hazard models revealed that lower levels of testosterone were related to higher mortality for the majority of disease categories in either an age-dependent or age-independent fashion. Analysis of all-cause mortality-which included deaths from any known disease-also revealed greater general risk for those with lower testosterone levels. For most disease categories, the hazard associated with low testosterone was especially evident at older ages when mortality from that particular ailment was already elevated. Notably, testosterone levels were not related to mortality risk for deaths unrelated to chronic disease (i.e. accidents and injuries). Conclusions and Implications: While the causal direction of relationships between testosterone and mortality risk remains unclear, these results may reflect the decline in testosterone that accompanies many disease states. Accordingly, the relationship between testosterone and male mortality may be indirect; ill individuals are expected to have both lower testosterone and higher mortality risk.

A multi-site study of the relationship between photoperiod and ovulation rate using Natural Cycles data.

Many species exhibit seasonal patterns of breeding. Although humans can shield themselves from many season-related stressors, they appear to exhibit seasonal patterns of investment in reproductive function nonetheless, with levels of sex steroid hormones being highest during the spring and summer months. The current research builds on this work, examining the relationship between day length and ovarian function in two large samples of women using data from the Natural Cycles birth control application in each Sweden and the United States. We hypothesized that longer days would predict higher ovulation rates and sexual motivation. Results revealed that increasing day length duration predicts increased ovulation rate and sexual behavior, even while controlling for other relevant factors. Results suggest that day length may contribute to observed variance in women's ovarian function and sexual desire.

Age-Dependent Relationships Between Disease Risk and Testosterone Levels: Relevance to COVID-19 Disease.

Testosterone levels in men appear to be prognostic of a number of disease outcomes, including severe COVID-19 disease. Testosterone levels naturally decline with age and are lower in individuals with a number of comorbidities and chronic conditions. Low testosterone may therefore be both a cause and a consequence of illness, including COVID-19 disease. The present project examines whether preexisting conditions for severe COVID-19 disease were themselves related to serum-free testosterone levels in men who had not been infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. A clinical risk score for severe COVID-19 disease was computed based on the results of previously published meta-analyses and cohort studies, and relationships between this score and testosterone levels were tested in 142 men ages 19 to 82 years. Greater burden of preexisting conditions for severe COVID-19 disease was related to lower testosterone levels among men younger than 40 years of age. In older men, the decrease in testosterone that accompanies aging attenuated the effect of the clinical risk score on free testosterone levels. Given that older age itself is a predictor of COVID-19 disease severity, these results together suggest that the presence of preexisting conditions may confound the relationship between testosterone levels and COVID-19 disease outcomes in men. Future research examining relationships among testosterone and outcomes related to infectious and chronic diseases should consider potential confounds, such as the role of preexisting conditions.

Tattooing as a phenotypic gambit.

OBJECTIVES: Tattooing is not an evolved behavior, but it may be a phenotypic gambit to highlight immunological health. Phenotypic gambits are traits or behaviors that appear costly but occur at high rates as a honing process of natural selection not constrained by genetics. Tattooing is an ancient practice that is increasing in popularity worldwide, but it involves wounding the body, which seems counterintuitive because it challenges the immune system and makes one more susceptible to infection. But tattooing may represent a costly honest signal of fitness by "upping the ante" in an era of hygiene or a means to stimulate the immune system in a way that improves and highlights underlying fitness. MATERIALS AND METHODS: We investigated this hypothesis by assessing bacteria killing activity (BKA) in saliva samples collected during two studies of tattooing (N = 40). We compared previous tattoo experience (extent of body tattooed and hours spent being tattooed) to BKA before and after getting a new tattoo. RESULTS: Tattoo experience positively predicts post-tattoo BKA (ß = 0.48, p = 0.01), suggesting that people with more tattoo experience have a relatively more immediate and active immune response than those with less tattoo experience. DISCUSSION: Tattoo experience may elevate innate immunological vigilance, which could aid in protecting against future dermal insults.

Longitudinal changes in COVID-19 concern and stress: Pandemic fatigue overrides individual differences in caution.

Background: Pandemic fatigue describes a phenomenon whereby individuals experience a decrease in COVID-19 concern over time, despite their risk for infection remaining stable, or even increasing. Individual differences in the experience of pandemic fatigue may have important implications for people's adherence to public health recommendations. Design and methods: Using data collected from a large community cohort in McLennan County, TX, longitudinal changes in COVID-19-related concern, stress, and affect across three appointments separated by approximately 4 weeks (July-November 2020) were examined. About 495, 349, and 286 participants completed one, two, and three appointments, respectively. Changes to stress physiology and local travel over time were also analyzed. Results: Results of a latent class growth analysis revealed four distinct classes of individuals: (a) low concern, low stress, (b) moderate concern, moderate stress, (c) moderate concern, low stress, and (d) high concern, high stress. Despite differences between latent classes in initial levels of concern, stress, and negative affect, levels of each variable decreased over time for all groups. While this reduction of concern did not coincide with changes in local travel, it was reflected in heart rate and blood pressure. Conclusions: Together, these results suggest a general trend of pandemic fatigue in the sample, even for those with moderate-to-high levels of initial COVID-19 stress and concern. Such findings may provide insights into the expected challenges of promoting compliance with public health recommendations as the pandemic continues.

Unrealistic Optimism and Risk for COVID-19 Disease.

Risk perception and consequently engagement in behaviors to avoid illness often do not match actual risk of infection, morbidity, and mortality. Unrealistic optimism occurs when individuals falsely believe that their personal outcomes will be more favorable than others' in the same risk category. Natural selection could favor overconfidence if its benefits, such as psychological resilience, outweigh its costs. However, just because optimism biases may have offered fitness advantages in our evolutionary past does not mean that they are always optimal. The current project examined relationships among personal risk for severe COVID-19, risk perceptions, and preventative behaviors. We predicted that those with higher risk of severe COVID-19 would exhibit unrealistic optimism and behave in ways inconsistent with their elevated risk of morbidity and mortality. Clinical risk scores for severe COVID-19 were calculated and compared with COVID-19 threat appraisal, compliance with shelter-in-place orders (March 13-May 22, 2020) and travel restrictions, compliance with public health recommendations, and potential covariates like self-rated knowledge about COVID-19 in a robust dataset including 492 participants from McLennan County, TX, USA. While those with high clinical risk acknowledged their greater likelihood of experiencing severe illness if infected, they actually reported lower perceived likelihood of becoming infected in the first place. While it is possible that those with higher clinical risk scores truly are less likely to become infected, the pattern and significance of these results held after controlling for possible occupational exposure, household size, and other factors related to infection probability. Higher clinical risk also predicted more recent travel within Texas and lower distress during the pandemic (i.e., feeling less stressed, depressed, and helpless). Additional behavioral data suggested that those with higher clinical risk scores did not generally behave differently than those with lower scores during the shelter-in-place order. While unrealistic optimism may provide some short-term psychological benefits, it could be dangerous due to improper assessment of hazardous situations; inferring that optimism bias has evolutionary origins does not mean that unrealistic optimism is "optimal" in every situation. This may be especially true when individuals face novel sources (or scales) of risk, such as a global pandemic.

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.