Reproductive suppression and longevity in human birth cohorts.

OBJECTIVES: Reproductive suppression refers to, among other phenomena, the termination of pregnancies in populations exposed to signals of death among young conspecifics. Extending the logic of reproduction suppression to humans has implications for health including that populations exposed to it should exhibit relatively great longevity. No research, however, has tested this prediction. METHODS: We apply time-series methods to vital statistics from Sweden for the years 1751 through 1800 to test if birth cohorts exposed in utero to reproductive suppression exhibited lifespan different from expected. We use the odds of death among Swedes age 1 to 9 years to gauge exposure. As the dependent variable, we use cohort life expectancy. Our methods ensure autocorrelation cannot spuriously induce associations nor reduce the efficiency of our estimates. RESULTS: Our findings imply that reproductive suppression increased the lifespan of 24 annual birth cohorts by at least 1.3 years over the 50-year test period, and that 12 of those cohorts exhibited increases of at least 1.7 years above expected. CONCLUSIONS: The best available data in which to search for evidence of reproductive suppression in humans support the argument that populations subjected to environments dangerous for children yield birth cohorts that exhibit unexpectedly great longevity.

Separating the Bruce and Trivers-Willard effects in theory and in human data.

OBJECTIVES: Theories of reproductive suppression predict that natural selection would conserve mechanisms that abort the gestation of offspring otherwise unlikely to thrive in prevailing environments. Research reports evidence among humans of at least two such mechanisms-the Trivers-Willard and Bruce Effects. No literature, however, compares the mechanisms nor estimates their relative contribution to observed characteristics of human birth cohorts. We describe similarities and differences between the Trivers-Willard and Bruce Effects and explore high quality historical data from Sweden to determine which mechanism better describes temporal variation in the ratio of males to females in birth cohorts. METHODS: We measure Trivers-Willard exposures with the death rate among women of reproductive age. We measure Bruce exposures with the death rate among children. We use time-series regression methods to estimate the relative contribution of the Trivers-Willard and Bruce Effects to temporal variation in historical Swedish secondary sex ratio data. RESULTS: We find that the Bruce Effect appears to be a better predictor of the secondary sex ratio than does the Trivers-Willard Effect. CONCLUSIONS: Attempts to identify mechanisms by which reproductive suppression affects fetal loss and characteristics of human birth cohorts should consider the Bruce Effect as an alternative to the Trivers-Willard Effect.

Multifactorial discrimination as a fundamental cause of mental health inequities.

BACKGROUND: The theory of fundamental causes explains why health disparities persist over time, even as risk factors, mechanisms, and diseases change. Using an intersectional framework, we evaluated multifactorial discrimination as a fundamental cause of mental health disparities. METHODS: Using baseline data from the Project STRIDE: Stress, Identity, and Mental Health study, we examined the health effects of discrimination among individuals who self-identified as lesbian, gay, or bisexual. We used logistic and linear regression to assess whether multifactorial discrimination met the four criteria designating a fundamental cause, namely that the cause: 1) influences multiple health outcomes, 2) affects multiple risk factors, 3) involves access to resources that can be leveraged to reduce consequences of disease, and 4) reproduces itself in varied contexts through changing mechanisms. RESULTS: Multifactorial discrimination predicted high depression scores, psychological well-being, and substance use disorder diagnosis. Discrimination was positively associated with risk factors for high depression scores: chronic strain and total number of stressful life events. Discrimination was associated with significantly lower levels of mastery and self-esteem, protective factors for depressive symptomatology. Even after controlling for risk factors, discrimination remained a significant predictor for high depression scores. Among subjects with low depression scores, multifactorial discrimination also predicted anxiety and aggregate mental health scores. CONCLUSIONS: Multifactorial discrimination should be considered a fundamental cause of mental health inequities and may be an important cause of broad health disparities among populations with intersecting social identities.

Twinning in Norway Following the Oslo Massacre: Evidence of a 'Bruce Effect' in Humans.

Emerging theory and empirical work suggest that the 'Bruce Effect', or the increase in spontaneous abortion observed in non-human species when environments become threatening to offspring survival, may also appear in humans. We argue that, if it does, the effect would appear in the odds of twins among male and female live births. We test the hypothesis, implied by our argument, that the odds of a twin among male infants in Norway fell below, while those among females rose above, expected levels among birth cohorts in gestation in July 2011 when a deranged man murdered 77 Norwegians, including many youths. Results support the hypothesis and imply that the Bruce Effect operates in women to autonomically raise the standard of fetal fitness necessary to extend the gestation of twins. This circumstance has implications for using twins to estimate the relative contributions of genes and environment to human responses to exogenous stimuli.

The influence of early maternal care on perceptual attentional set shifting and stress reactivity in adult rats.

Stress influences a wide variety of outcomes including cognitive processing. In the rat, early life maternal care can influence developing offspring to affect both stress reactivity and cognitive processes in adulthood. The current study assessed if variations in early life maternal care can influence cognitive performance on a task, the ability to switch cognitive sets, dependent on the medial prefrontal cortex. Early in life, offspring was reared under High or Low maternal Licking conditions. As adults, they were trained daily and then tested on an attentional set-shifting task (ASST), which targets cognitive flexibility in rodents. Stress-sensitive behavioral and neural markers were assayed before and after the ASST. High and Low Licking offspring performed equally well on the ASST despite initial, but not later, differences in stress axis functioning. These results suggest that early life maternal care does not impact the accuracy of attentional set-shifting in rats. These findings may be of particular importance for those interested in the relationship between early life experience and adult cognitive function.

"Racial mortality inversion": Black-white disparities in mortality among people experiencing homelessness in the United States.

Disparities in mortality between Black and White people have long been observed. These disparities persist at all income levels. However, similar patterns in racial mortality disparities are not observed among people experiencing homelessness. Instead, studies in a handful of cities show a reversal in the Black-White mortality disparity in the United States: Black people experiencing homelessness are less likely to die compared to White people experiencing homelessness. We propose a theory of "racial mortality inversion" and test whether inverted Black-White mortality patterns are observable in homeless populations throughout the United States. Using a novel dataset of 18,618 homeless decedents in 20 localities across 10 states and the District of Columbia, we find consistent evidence for "racial mortality inversion" across time and place. Between 2015 and 2020, the aggregate White homeless mortality rate was 67.8%-138.4% higher than the rate for the Black homeless population. Inverted racial mortality rates were observed in all 20 localities and in nearly every year. Across the entire sample, higher average ages of death were also observed for Black people compared to White people experiencing homelessness in 5 of 6 years, though racial inversion in age was not consistent across localities. These findings offer novel insight into racial health disparities among people experiencing homelessness and may inform policies and programs that seek to prevent homelessness and homeless mortality across racial groups.

Family adversity and autonomic reactivity association with immune changes in HIV-affected school children.

OBJECTIVE: To explore whether primary school entry is associated with changes in immune system parameters in HIV-affected children. HIV-affected children are vulnerable to psychosocial stressors, regardless of their own HIV serological status. METHODS: Data from 38 HIV-positive and 29 HIV-negative children born to seropositive women were obtained. Measures included family adversity questionnaires, autonomic nervous system (ANS) reactivity, and enumerative and functional changes in peripheral blood immune parameters. RESULTS: In comparison with children who were HIV-negative, children who were HIV-positive at baseline had fewer CD4(+) T lymphocytes (mean [M] = 916 versus 1206 cells/mm(3) × 10(3); F = 7.8, p = .007), more CD8(+) cells (M = 1046 versus 720 cells/mm(3) × 10(3); F = 7.98, p = .006), and diminished natural killer cell cytotoxicity (M = -0.29 versus 0.41; F = 8.87, p = .004). School entry was associated with changes in immune parameters, but HIV status was not associated with the magnitude of changes. Changes in immune parameters after school entry were associated with family stress and preschool entry ANS reactivity. Highly ANS reactive children had either the greatest increase in CD8(+) cells after school entry or the greatest decrease, depending on reported levels of family adversity (B = 215.35; t = 3.74, p < .001). Changes in functional immune assays were significantly associated with the interactions between HIV status and ANS reactivity. CONCLUSIONS: These results suggest that autonomic reactivity is associated with increased immunological sensitivity to adverse or challenging social contexts among children affected by HIV.

Deaths of profound despair: A retrospective cohort study of mortality among people experiencing homelessness.

INTRODUCTION: The number of people dying while unhoused is increasing nationally. In Santa Clara County (SCC), deaths of unhoused people have almost tripled in 9 years. This is a retrospective cohort study examining mortality trends among unhoused people in SCC. The objective of the study is to characterize mortality outcomes in the unhoused population, and compare these to the SCC general population. MATERIALS AND METHODS: We obtained data from the SCC Medical Examiner-Coroner's Office on unhoused people's deaths that occurred between 2011-2019. We analyzed demographic trends and cause of death, compared to mortality data on the SCC general population obtained from CDC databases. We also compared rates of deaths of despair. RESULTS: There were a total of 974 unhoused deaths in the SCC cohort. The unadjusted mortality rate among unhoused people is higher than the general population, and unhoused mortality has increased over time. The standardized mortality ratio for unhoused people is 3.8, compared to the general population in SCC. The most frequent age of death among unhoused people was between 55-64 years old (31.3%), followed by 45-54 (27.5%), compared to 85+ in the general population (38.3%). Over ninety percent of deaths in the general population were due to illness. In contrast, 38.2% of unhoused deaths were due to substance use, 32.0% illness, 19.0% injury, 4.2% homicide, and 4.1% suicide. The proportion of deaths of despair was 9-fold higher in the unhoused cohort compared to the housed cohort. DISCUSSION: Homelessness has profound impacts on health, as people who are unhoused are dying 20 years younger, with higher rates of injurious, treatable, and preventable causes, than people in the general population. System-level, inter-agency interventions are needed. Local governments need to systematically collect housing status at death to monitor mortality patterns among unhoused people, and adapt public health systems to prevent rising unhoused deaths.

A test of maternal human chorionic gonadotropin during pregnancy as an adaptive filter of human gestations.

The risk of abnormalities and morbidity among live births increases with advanced maternal age. Explanations for this elevated morbidity invoke several maternal mechanisms. The relaxed filter stringency (RFS) hypothesis asserts that mothers, nearing the end of their reproductive lifespan, reduce the stringency of a screen of offspring quality in utero based on life-history traits of parity and interbirth interval (IBI). A separate line of research implicates human chorionic gonadotropin (hCG) during pregnancy as a signal of offspring quality. We test the RFS hypothesis directly by examining whether the difference in gestational hCG across consecutive live births varies positively with the mother's number of previous live births but inversely with her most recent IBI. We applied multivariable regression methods to a unique dataset of gestational hCG for over 500 000 live births from 2002 to 2007. The difference in gestational hCG across mothers' consecutive live births varies positively with both mothers' parity and IBI. These associations remain similar among older mothers (35+ years). Findings support the RFS hypothesis for the parity expectation but not for the IBI expectation. Further evidence for the RFS hypothesis among contemporary human gestations would have to invoke screening mechanisms other than hCG.

Invisibility as a structural determinant: Mortality outcomes of Asians and Pacific Islanders experiencing homelessness.

Introduction: Asians and Pacific Islanders (APIs) who are experiencing homelessness are situated in a social intersection that has rendered them unrecognized and therefore vulnerable. There has been increasing attention to racial disparities in homelessness, but research into API homelessness is exceedingly rare, despite rapidly growing populations. The purpose of this study is to examine the causes of death among APIs who died while homeless in Santa Clara County (SCC) and compare these causes to other racial groups. Materials and methods: We report on data obtained from the SCC Medical Examiner-Coroner's Office on unhoused people's deaths that occurred between 2011 and 2021 (n = 1,394), including data on deaths of APIs experiencing homelessness (n = 87). Results: APIs comprised 6.2% of total deaths of unhoused people. APIs died less often of causes related to drug/alcohol use than all other racial groups (24.1, compared to 39.3%), and there was a trend toward more API deaths from injuries or illnesses. When APIs were disaggregated into sub-groups (East/Southeast Asian, South Asian, Pacific Islander), there were notable mortality differences in cause of death, age, and sex. Discussion: We argue that invisibility is a structural determinant of health that homeless APIs face. Though relatively small in numbers, APIs who are invisible may experience increased social isolation and, subsequently, specific increased mortality risks. To understand the health outcomes of unhoused APIs, it is essential that researchers and policymakers recognize API homelessness and gather and report disaggregated races and ethnicities.

African American Unemployment and the Disparity in Periviable Births.

Periviable infants (i.e., born before 26 complete weeks of gestation) represent fewer than .5% of births in the US but account for 40% of infant mortality and 20% of billed hospital obstetric costs. African American women contribute about 14% of live births in the US, but these include nearly a third of the country's periviable births. Consistent with theory and with periviable births among other race/ethnicity groups, males predominate among African American periviable births in stressed populations. We test the hypothesis that the disparity in periviable male births among African American and non-Hispanic white populations responds to the African American unemployment rate because that indicator not only traces, but also contributes to, the prevalence of stress in the population. We use time-series methods that control for autocorrelation including secular trends, seasonality, and the tendency to remain elevated or depressed after high or low values. The racial disparity in male periviable birth increases by 4.45% for each percentage point increase in the unemployment rate of African Americans above its expected value. We infer that unemployment-a population stressor over which our institutions exercise considerable control-affects the disparity between African American and non-Hispanic white periviable births in the US.

The health effects of economic decline.

Political pronouncements and policy statements include much conjecture concerning the health and behavioral effects of economic decline. We both summarize empirical research concerned with those effects and suggest questions for future research priorities. We separate the studies into groups defined by questions asked, mechanisms invoked, and outcomes studied. We conclude that although much research shows that undesirable job and financial experiences increase the risk of psychological and behavioral disorder, many other suspected associations remain poorly studied or unsupported. The intuition that mortality increases when the economy declines, for example, appears wrong. We note that the research informs public health programming by identifying risk factors, such as job loss, made more frequent by economic decline. The promise that the research would identify health costs and benefits of economic policy choices, however, remains unfulfilled and will likely remain so without stronger theory and greater methodological agreement.

The social environment and IL-6 in rats and humans.

Inflammatory cytokine levels predict a wide range of human diseases including depression, cardiovascular disease, type 2 diabetes, autoimmune disease, general morbidity, and mortality. Stress and social experiences throughout the lifecourse have been associated with inflammatory processes. We conducted studies in humans and laboratory rats to examine the effect of early life experience and adult social position in predicting IL-6 levels. Human participants reported family homeownership during their childhood and current subjective social status. Interleukin-6 (IL-6) was measured from oral mucosal transudate. Rats were housed in groups of three, matched for quality of maternal care received. Social status was assessed via competition for resources, and plasma IL-6 was assessed in adulthood. In both humans and rats, we identified an interaction effect; early social experience moderated the effect of adult social status on IL-6 levels. Rats that experienced low levels of maternal care and people with low childhood socioeconomic status represented both the highest and lowest levels of IL-6 in adulthood, depending on their social status as young adults. The predicted interaction held for non-Hispanic people, but did not occur among Hispanic individuals. Adversity early in life may not have a monotonically negative effect on adult health, but may alter biological sensitivity to later social experiences.

Food insecurity in older female mice affects food consumption, coping behaviors, and memory.

Food insecurity correlates with poor physical and mental health in older individuals, but has not been studied in a laboratory animal model. This explorative study developed a laboratory mouse model for analyzing the impact of food insecurity on food consumption, stress coping mechanisms, exploratory behavior, and memory. 18-month-old CD-1 female mice were assigned to either the food insecurity exposure condition (31 mice, 8 cages) or the control condition (34 mice, 8 cages) by cage. Over four weeks, the mice that were exposed to food insecurity received varied, unpredictable portions of their baseline food consumption (50%, 75%, 125%, 150% of baseline) for four days, followed by ad libitum access for three days, to approximate the inconsistent access to food observed in households experiencing food insecurity. Behavioral tasks were conducted before and after food insecurity exposure. Mice in the food insecurity exposure condition ate less compared to control mice during food insecurity (two-way ANOVA: group x time interaction: F7,93 = 10.95, P < 0.01) but ate more when given access to high fat food (two-way ANOVA, group x time interaction: F1,14 = 11.14, P < 0.01). Mice exposed to food insecurity increased active escaping behaviors in the forced swim test (repeated measures two-way ANOVA, group x time interaction: F1,63 = 5.40, P = 0.023). Exploratory behaviors were unaffected by food insecurity. Mice exposed to food insecurity showed a reduction in memory (repeated measures two-way ANOVA, group x time interaction: F1,61 = 4.81, P = 0.037). These results suggest that exposure to food insecurity is associated with differences in food consumption patterns, active coping mechanisms, and memory. The behavioral changes associated with food insecurity may inform research on food insecurity's impact on health in elderly humans.

Selection in utero: a biological response to mass layoffs.

Most research describing the biological response to unemployment appears appropriately motivated by clinical or public health concerns and focuses on death, disease, and medical care. We argue that expanding the work to include other outcomes could contribute to basic science. As an example, we use the response to mass layoffs to discriminate between two explanations of low ratios of male to female live births in stressed populations. One explanation asserts that ambient stressors reduce the ratio of males to females conceived. The other argues that the maternal stress response selects against males in utero. We show that selection in utero better explains the observed data. We conclude that human adaptation to the economic environment deserves scrutiny from a wider array of scientists than it now receives.

Early life adversity increases the salience of later life stress: an investigation of interactive effects in the PSID.

A large body of evidence has shown that stress throughout life is associated with health trajectories, but the combination of adverse experiences at different stages of the life course is not yet well understood. This study examines the interactions between childhood adversity, adulthood adversity, and adult physical and mental health. Using data from The Childhood Retrospective Circumstances Study (CRCS) supplement to the Panel Study of Income Dynamics (PSID), we created indices of early life adversity (EAI) and adult adversity (AAI). We used logistic regression to examine the effects of EAI and AAI, adjusting for age, sex, race/ethnicity, health behaviors, and childhood health as covariates in all models. We repeated this analysis for the outcomes of fair/poor health, two or more chronic conditions, and psychological distress in adulthood. For all the three outcomes, our findings suggest increasing salience of adult adversity among those who experienced higher levels of early adversity. Individuals with high EAI and high AAI exhibited the highest odds of fair/poor health (OR = 5.71), chronic conditions (OR = 3.06), and psychological distress (OR = 13.08) compared to those with low EAI and low AAI. These findings are consistent with the accumulation of risk or dual risk model of stress and health. Adversity in childhood amplifies the health risks associated with stress in adulthood for multiple health outcomes.

From paradox to disparity: trends in neonatal death in very low birth weight non-Hispanic black and white infants, 1989-2004.

OBJECTIVES: To examine temporal trends in race-specific neonatal death in California to determine whether the overall decline in mortality attenuated the paradoxical survival advantage of very low birth weight (VLBW; birth weight < 1500 g) non-Hispanic black infants relative to VLBW non-Hispanic white infants. STUDY DESIGN: The data set comprised the California birth cohort file on non-Hispanic black and non-Hispanic white VLBW neonatal mortality for 1989-2004. Logistic regression methods were used to control for potentially confounding maternal characteristics. RESULTS: In 1989 and 1990, non-Hispanic black VLBW infants demonstrated a paradox of lower neonatal mortality (adjusted odds ratio [aOR] = 0.84; 95% confidence interval [CI] = 0.75-0.94). This survival advantage disappeared after 1991, however. In 2003 and 2004, the incidence of neonatal mortality increased in non-Hispanic black VLBW infants but decreased in non-Hispanic white VLBW infants, resulting in a racial disparity (aOR = 1.34; 95% CI = 1.14-1.56). CONCLUSIONS: An initial survival paradox transformed into a disparity. The magnitude of this non-Hispanic black/non-Hispanic white VLBW disparity rose to its highest levels in the last 2 years of the study period. Moreover, the steady mortality increase in VLBW non-Hispanic black VLBW infants since 2001 reversed the secular decline in neonatal mortality in this population. Our findings underscore the need to augment strategies to improve the health trajectory of gestation in non-Hispanic black women.

A sex-specific test of selection in utero.

We find support for the hypothesis that changes in the monthly odds of a twin among live-born males predict subsequent and opposite changes in the odds of a twin among live-born females. The hypothesis arises from the long standing argument that natural selection has conserved mechanisms by which pregnant women in stressed populations spontaneously abort fetuses least likely to yield grandchildren. Previous attempts to empirically test this argument focus almost entirely on males. We contribute to the literature by showing that, consistent with the logic of natural selection, maternal adaptations to environmental changes likely have effects on the survival of both male and female conceptuses and fetuses.

Gender-specific selection in utero among contemporary human birth cohorts.

Much literature argues that natural selection has conserved mechanisms by which stressed females cull frail males in utero. This argument implies that males from low sex ratio birth cohorts should, on average, live longer than those from high sex ratio cohorts. Research reports such associations but these tests use completed lifespan as the outcome and, therefore, must end with cohorts born in 1913 because too many males survive from more contemporary cohorts to determine average lifespan. The empirical literature does not, therefore, address whether selection affects male mortality in contemporary cohorts. We apply time-series methods to monthly cohorts born in California between 1989 and 2003 to measure the association between the ratio of male to female live births and infant mortality, controlling for all forms of autocorrelation that induce spurious correlations. Consistent with theories of selection in utero, we find a positive correlation between cohort sex ratio and male infant mortality. The results suggest that natural selection conserved the stress mechanism in females to end the gestation of relatively less fit males and that this mechanism manifests itself in contemporary human societies.