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.

Rural-urban disparities in psychosocial functioning in epithelial ovarian cancer patients.

OBJECTIVE: Although rural residence has been related to health disparities in cancer patients, little is known about how rural residence impacts mental health and quality of life (QOL) in ovarian cancer patients over time. This prospective longitudinal study investigated mental health and QOL of ovarian cancer patients in the first-year post-diagnosis. METHOD: Women with suspected ovarian cancer completed psychosocial surveys pre-surgery, at 6 months and one-year; clinical data were obtained from medical records. Histologically confirmed high grade epithelial ovarian cancer patients were eligible. Rural/urban residence was categorized from patient counties using the USDA Rural-Urban Continuum Codes. Linear mixed effects models examined differences in psychosocial measures over time, adjusting for covariates. RESULTS: Although disparities were not observed at study entry for any psychosocial variable (all p-values >0.22), urban patients showed greater improvement in total distress over the year following diagnosis than rural patients (p = 0.025) and were significantly less distressed at one year (p = 0.03). Urban patients had a more consistent QOL improvement than their rural counterparts (p = 0.006). There were no differences in the course of depressive symptoms over the year (p = 0.17). Social support of urban patients at 12 months was significantly higher than that of rural patients (p = 0.04). CONCLUSION: Rural patients reported less improvement in psychological functioning in the year following diagnosis than their urban counterparts. Clinicians should be aware of rurality as a potential risk factor for ongoing distress. Future studies should examine causes of these health disparities and potential long-term inequities and develop interventions to address these issues.

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.

Greater lifetime stressor exposure is associated with poorer mental health among sexual minority people of color.

BACKGROUND: Research has shown that sexual minority people of color experience pervasive and sometimes severe life stressors that increase their risk of experiencing mental health problems, and that can contribute to lifelong health disparities. However, no studies in this population have investigated stressor exposure occurring over the entire lifespan. Moreover, it remains unknown whether these stressor-health effects differ based on the timing or types of stressors experienced. PURPOSE: The purpose of this study is to examine how cumulative lifetime stressor exposure is associated with mental health among Black, Latinx, and biracial Black-Latinx sexual minority persons. METHOD: Participants were 285 ethnic/racial minority young adults (Mage = 25.18 years old, SD = 1.94, age range = 19-29 years), who completed the Stress and Adversity Inventory for Adults to assess for retrospective reports of lifetime stressor count and severity. The Brief Symptom Inventory was used to assess participants' symptoms of anxiety, depression, and somatization, which were the main outcomes. Most participants identified as cisgender male (94.7%) and gay (74.2%), with the remaining participants identifying as transgender or genderqueer/nonbinary for gender and bisexual/pansexual, queer, or another sexual orientation. RESULTS: Multiple regression analyses indicated that experiencing more-and more severe-stressors across the lifespan was related to greater anxiety, depressive, and somatization symptoms. These effects were robust while controlling for race/ethnicity, sexual orientation, education, and employment status, and they differed based on stressor exposure timing, type, primary life domain, and core social-psychological characteristic. CONCLUSION: Greater cumulative lifetime stressor exposure is related to poorer mental health among sexual minority people of color. Screening for lifetime stressors may thus help identify at-risk persons and provide an opportunity to intervene to help mitigate or prevent mental health disparities in multiply stigmatized adults.

Inflammation and depression symptoms are most strongly associated for Black adults.

Although race/ethnicity is associated with substantial differences in risk for depression and other diseases of aging in the United States, the processes underlying these health disparities remain poorly understood. We addressed this issue by examining how levels of a robust marker of inflammatory activity, C-reactive protein (CRP), and depression symptoms varied across racial/ethnic groups. Additionally, we tested whether the inflammation-depression association differed across groups. Data were drawn from the Chicago Community Adult Health Survey, an epidemiological survey examining biopsychosocial factors affecting health and well-being. Participants were 3105 Chicago community adults, of which 610 provided blood samples and were included in analyses. C-reactive protein was assayed from blood samples, and depression symptoms were assessed using the 11-item Center for Epidemiologic Studies-Depression scale. Race/ethnicity was self-reported and consisted of Black, Hispanic, White, and other racial/ethnic groups. Results revealed that these racial/ethnic groups differed in terms of both their CRP and depression levels. Specifically, Black Americans exhibited higher levels of CRP as compared to White and other race/ethnicity Americans. Moreover, Black Americans exhibited more depression symptoms than Hispanic Americans. Finally, we found that inflammatory levels were strongly related to depression symptoms but only for Black Americans, with CRP alone accounting for 8% of the variance in depression symptoms in this subgroup. These data thus point to a biological process that may help to explain disparities in mental health outcomes across race/ethnicity in the United States. At the same time, additional research is needed to understand the social and structural factors driving these effects.

Cumulative lifetime stressor exposure assessed by the STRAIN predicts economic ambiguity aversion.

Uncertainty is inherent in most decisions humans make. Economists distinguish between two types of decision-making under non-certain conditions: those involving risk (i.e., known outcome probabilities) and those that involve ambiguity (i.e., unknown outcome probabilities). Prior research has identified individual differences that explain risk preferences, but little is known about factors associated with ambiguity aversion. Here, we hypothesized that cumulative exposure to major psychosocial stressors over the lifespan might be one factor that predicts individuals' ambiguity aversion. Across two studies (Study 1: n = 58, Mage = 25.7; Study 2: n = 188, Mage = 39.81), we used a comprehensive lifetime stressor exposure inventory (i.e., the Stress and Adversity Inventory for Adults, or STRAIN) and a standard economic approach to quantify risk and ambiguity preferences. Greater lifetime stressor exposure as measured by the STRAIN, particularly in early life, was associated with higher aversion to ambiguity but not risk preferences.

Exploring joint HPA-inflammatory stress response profiles in adolescent girls: Implications for developmental models of neuroendocrine dysregulation.

Prior research has struggled to differentiate cortisol stress response patterns reflective of well-regulated versus dysregulated hypothalamic-pituitary-adrenal (HPA) axis function among adolescents. Here, we show how exploring profiles of joint HPA-inflammatory stress responsivity, and linking those profiles to pubertal development and peer stress exposure may aid such distinction. Adolescent girls (N = 157, Mage  = 14.72 years, SD = 1.38) at risk for psychopathology completed assessments of salivary cortisol and pro-inflammatory cytokines (i.e., tumor necrosis factor-α, interleukin-1ß, and interleukin-6) prior to and following the Trier Social Stress Test. Adolescents, a close friend, and a caregiver completed questionnaire measures of peer stress and pubertal status. Multitrajectory modeling of adolescents' cortisol and cytokine levels revealed three profiles: low cortisol response-stably low cytokine (n = 75), high cortisol response-stably moderate cytokine (n = 47), and low cortisol response-stably high cytokine (n = 35). Relative to low cortisol response-stably low cytokine, adolescents exhibiting the high cortisol response-stably moderate cytokine profile were more advanced in their pubertal development, but presented with similarly low levels of peer stress exposure. Despite showing cortisol responses that were indistinguishable from low cortisol response-stably low cytokine, adolescents exhibiting the low cortisol response-stably high cytokine profile were more pubertally advanced, but also more likely to have experienced chronic peer strain (self-report) and relational peer victimization (close friend-report). These findings thus illustrate the potential value of taking a multisystem approach to studying adolescent stress responsivity and underscore the importance of considering developmental and social factors when interpreting cortisol stress response patterns. Ultimately, such work may help inform developmental models of neuroendocrine dysregulation and related risk for psychopathology.

Effects of Early Life Adversity on Pubertal Timing and Tempo in Black and White Girls: The National Growth and Health Study.

OBJECTIVE: Although exposure to abuse in early life predicts earlier pubertal timing, especially for girls, it is unclear if this association generalizes to nonabuse stressors. In addition, the impact of race on the stress-maturation association remains unknown. To address these issues, we examined whether race moderates the effects of early adversity on pubertal timing and tempo using a longitudinal study design. METHODS: In a cohort of 9- and 10-year-old Black and White girls, pubertal (areolar and pubic hair) maturation was assessed annually for 7 years. In adulthood, 368 participants (186 Black, 182 White) reported on abuse and nonabuse stressors they experienced from ages 0 to 12 years. RESULTS: Early life abuse was associated with earlier pubertal timing, as indexed by younger age at menarche (b = -0.22, p = .005, 95% confidence interval [CI] = -0.39 to -0.06) and greater pubic hair development (b = 0.11, p = .003, 95% CI = 0.04 to 0.18), in addition to slower pubertal tempo, as indexed by slower rate of pubic hair (b = -0.03, p < .001, 95% CI = -0.05 to -0.01) and areolar (b = -0.02, p = .02, 95% CI = -0.03 to -0.003) development. These associations were not found for nonabuse adversity. Black girls with early life abuse had greater pubic hair development (b = 0.23, p < .001, 95% CI = 0.12 to 0.35) and were slower in pubic hair tempo (b = -0.07, p < .001, 95% CI = -0.09 to -0.04) than their White counterparts. CONCLUSIONS: Screening for early life abuse may help address health disparities related to earlier pubertal timing.

Beyond WEIRD: Associations between socioeconomic status, gender, lifetime stress exposure, and depression in Madagascar.

OBJECTIVE: Although research has examined associations between socioeconomic status (SES), gender, and acute and chronic life stressors in depression, most studies have been conducted in Western, educated, industrialized, rich, democratic (WEIRD) populations. METHOD: We addressed this issue by interviewing 65 adults (55 women, M age = 37) living in Madagascar, a typical low- and middle-income country. RESULTS: As hypothesized, women experienced more life stressors and depressive symptoms, on average, than men, as did those from lower (vs. higher) SES backgrounds. Additionally, lifetime stress exposure was associated with greater symptoms of depression, accounting for 19% of the variability in depressive symptom levels. These effects differed for acute versus chronic and distal versus recent stressors. Finally, stress exposure significantly mediated the relation between SES and gender on depressive symptoms, accounting for 24.0%-70.8% of the SES/gender-depression association depending on stressor type. CONCLUSION: These data extend prior research by describing how social stratification and gender relate to lifetime stress exposure and depressive symptoms in a non-WEIRD population.

Mental health and clinical psychological science in the time of COVID-19: Challenges, opportunities, and a call to action.

COVID-19 presents significant social, economic, and medical challenges. Because COVID-19 has already begun to precipitate huge increases in mental health problems, clinical psychological science must assert a leadership role in guiding a national response to this secondary crisis. In this article, COVID-19 is conceptualized as a unique, compounding, multidimensional stressor that will create a vast need for intervention and necessitate new paradigms for mental health service delivery and training. Urgent challenge areas across developmental periods are discussed, followed by a review of psychological symptoms that likely will increase in prevalence and require innovative solutions in both science and practice. Implications for new research directions, clinical approaches, and policy issues are discussed to highlight the opportunities for clinical psychological science to emerge as an updated, contemporary field capable of addressing the burden of mental illness and distress in the wake of COVID-19 and beyond. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Stress and Health in Nursing Students: The Nurse Engagement and Wellness Study.

BACKGROUND: Evidence suggests that behavioral, social, and environmental factors may modify the effects of life stress on health and performance of new nurses as they transition to hospitals. OBJECTIVES: The aim of this study was to describe the methods of a project designed to investigate the role of social, behavioral, and environmental factors in modifying the adverse effects of stress on new nurses and to discuss demographic, health, and life stress characteristics of the cohort at baseline. METHODS: A prospective cohort design was used to conduct a comprehensive assessment of health endpoints, life stress, behaviors, personal traits, social factors, indicators of engagement and performance, and environmental exposures in nursing students. Adjusted odds ratios and analyses of covariance were used to examine associations between these factors at baseline. RESULTS: Health indicators in the cohort were comparable or better than in the broader United States population, and lifetime stress exposure was lower than among students from other majors. Exposure to more lifetime stressors was associated with greater risk for various health conditions, including hypertension, diabetes, and depression. Conversely, better social, environmental, behavioral, and personal profiles were associated with protective effects for the same health conditions. DISCUSSION: These data comprehensively summarize the lives of predominately Hispanic nursing students and highlight risk and resilience factors associated with their health and well-being. The findings are timely, as the nursing field diversifies in preparation to care for a diverse and aging population. Comprehensively assessing stress-health relationships among student nurses ought to inform the policies, practices, and curricula of nursing schools to better prepare nurses to thrive in the often-strenuous healthcare environment.

Socioeconomic status, social-cultural values, life stress, and health behaviors in a national sample of adolescents.

Adolescence is a developmental period during which time individuals adopt health behaviors that affect their lifelong health and disease risk. Socioeconomic status, social-cultural values, and stress have all been hypothesized to play a role in this association, but very few studies have examined how these factors interrelate and explain differences in health behaviors in adolescence. To address this issue, we assessed youths' socioeconomic status, social-cultural values, life stress levels across seven domains, and health behaviors in a national sample of 1,830 high school seniors living in the four largest cities in Croatia. Structural equation modelling examined the extent to which stress mediates the effects of socioeconomic status and social-cultural values on positive and negative health behaviors. As hypothesized, stress levels significantly mediated associations between youths' socioeconomic status, social-cultural values, and healthy and unhealthy habits. Additionally, whereas better socioeconomic status predicted less stress, greater social-cultural value on achieving a "good life" predicted more stress. More stress, in turn, was associated with engaging in fewer healthy behaviors for both males and females, and more unhealthy behaviors for males. Socioeconomic status and social-cultural values thus appear to influence stress levels, which may in turn affect adolescents' health behaviors and, potentially, their lifespan health.

Lifetime Stress Exposure and Health: A Review of Contemporary Assessment Methods and Biological Mechanisms.

Life stress is a central construct in health research because it is associated with increased risk for a variety of serious mental and physical health problems, including anxiety disorders, depression, cardiovascular disease, autoimmune disorders, Alzheimer's disease, certain cancers, and other diseases of aging. In this review, we examine how lifetime stress exposure contributes to elevated disease risk, and explore ongoing measurement and scientific issues related to this topic. To accomplish these goals, we first review existing instruments that have been developed for assessing perceived stress, self-reported life events, interviewer-assessed life stressors, and lifetime stress exposure. Next, we describe laboratory-based tasks that have been used for characterizing individual differences in psychological and biological stress reactivity. These methods have yielded an enormous amount of data showing how life stress influences the activity of the hypothalamic-pituitary-adrenal axis, hypothalamic-pituitary-gonadal axis, sympathetic-adrenal-medullary axis, and immune system, and how such processes can in turn cause allostatic load and biological embedding of the stress effect at the level of the human brain and genome. At the same time, many critical measurement and scientific issues remain unresolved, and we discuss these topics last while describing some pressing issues and opportunities for future research on stress and health.

Measuring lifetime stress exposure and protective factors in life course research on racial inequality and birth outcomes.

There has been a long-standing interest in better understanding how social factors contribute to racial disparities in health, including birth outcomes. A recent emphasis in this context has been on identifying the effects of stress exposure and protective factors experienced over the entire lifetime. Yet despite repeated calls for a life course approach to research on this topic, very few studies have actually assessed how stressors and protective factors occurring over women's lives relate to birth outcomes. We discuss this issue here by describing how challenges in the measurement of lifetime stress exposure and protective factors have prevented researchers from developing an empirically-based life course perspective on health. First, we summarize prevailing views on racial inequality and birth outcomes; second, we discuss measurement challenges that exist in this context; and finally, we describe both new tools and needed tools for assessing lifetime stress exposure and suggest opportunities for integrating information on stress exposure and psychosocial protective factors. We conclude that more studies are needed that integrate information about lifetime stress exposures and the protective factors that promote resilience against such exposures to inform policy and practice recommendations to reduce racial disparities in birth outcomes.

Neural mechanisms linking social status and inflammatory responses to social stress.

Social stratification has important implications for health and well-being, with individuals lower in standing in a hierarchy experiencing worse outcomes than those higher up the social ladder. Separate lines of past research suggest that alterations in inflammatory processes and neural responses to threat may link lower social status with poorer outcomes. This study was designed to bridge these literatures to investigate the neurocognitive mechanisms linking subjective social status and inflammation. Thirty-one participants reported their subjective social status, and underwent a functional magnetic resonance imaging scan while they were socially evaluated. Participants also provided blood samples before and after the stressor, which were analysed for changes in inflammation. Results showed that lower subjective social status was associated with greater increases in inflammation. Neuroimaging data revealed lower subjective social status was associated with greater neural activity in the dorsomedial prefrontal cortex (DMPFC) in response to negative feedback. Finally, results indicated that activation in the DMPFC in response to negative feedback mediated the relation between social status and increases in inflammatory activity. This study provides the first evidence of a neurocognitive pathway linking subjective social status and inflammation, thus furthering our understanding of how social hierarchies shape neural and physiological responses to social interactions.