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Evolutionary medicine – i.e. the application of insights from evolution and ecology to biomedicine – has tremendous untapped potential to spark transformational innovation in biomedical research, clinical care and public health. Fundamentally, a systematic mapping across the full diversity of life is required to identify animal model systems for disease vulnerability, resistance, and counter-resistance that could lead to novel clinical treatments. Evolutionary dynamics should guide novel therapeutic approaches that target the development of treatment resistance in cancers (e.g., via adaptive or extinction therapy) and antimicrobial resistance (e.g., via innovations in chemistry, antimicrobial usage, and phage therapy). With respect to public health, the insight that many modern human pathologies (e.g., obesity) result from mismatches between the ecologies in which we evolved and our modern environments has important implications for disease prevention. Life-history evolution can also shed important light on patterns of disease burden, for example in reproductive health. Experience during the COVID-19 (SARS-CoV-2) pandemic has underlined the critical role of evolutionary dynamics (e.g., with respect to virulence and transmissibility) in predicting and managing this and future pandemics, and in using evolutionary principles to understand and address aspects of human behavior that impede biomedical innovation and public health (e.g., unhealthy behaviors and vaccine hesitancy). In conclusion, greater interdisciplinary collaboration is vital to systematically leverage the insight-generating power of evolutionary medicine to better understand, prevent, and treat existing and emerging threats to human, animal, and planetary health.

Objectives Two-thirds of individuals living with Alzheimer’s disease are women. Declining estrogen levels influence mood and cognition. Cumulative lifetime estrogen exposure (CLEE) correlates with cognition later in life. We examined the relationship of CLEE to depression and cognition in older women with major depression compared to non-depressed women. Design Older women (age ≥60 years) with depression were compared to non-depressed women using a lifetime estrogen exposure questionnaire. CLEE was defined as combined durations of reproductive span (age of menopause minus age of menarche) and any post-menopausal hormone replacement therapy use. Higher vs lower CLEE groups were based on a median of 474 months of estrogen exposure. Setting University hospital outpatient research program Participants 135 women ≥60 years; 64 depressed and 71 non-depressed Measurments Participants completed a comprehensive cognitive test battery. General linear models were used to examine the association between cognitive domain scores and CLEE in depressed and non-depressed women, controlling for age, education, and ethnicity. Results Depressed and non-depressed groups had significantly different levels of CLEE, measured in months: mean 495.7 (SD 108.6) vs 456.4 (SD 66.0) months, F(1,130) = 5.01, p = .03. Within the non-depressed participants, higher CLEE was associated with improved delayed recall (F(1,59) = 5.94, p = .02, effect size = .61), while no such relationship was observed in the depressed group. Conclusion Higher CLEE was associated with improvement in delayed recall among non-depressed, but not among depressed participants. This suggests a protective role of estrogen on memory in non-depressed older postmenopausal women. Further research should examine the role of the CLEE in antidepressant response and cognitive decline.

Objective: Research suggests that the 2016 U.S. election was a potential stressor among Latinos residing in the U.S. Sociopolitical stressors targeted toward ethnic minority communities and become embodied through psychosocial distress. The current study investigates if and how sociopolitical stressors related to the 45th President, Donald Trump, and his administration are associated with psychological distress in early pregnancy of Latina women living in Southern California during the second half of his term. Methods: This cross-sectional analysis uses data from the Mothers’ Cultural Experiences study (n=90) collected from December 2018 to March 2020. Psychological distress was assessed in three domains: depression, state anxiety, and pregnancy-related anxiety. Sociopolitical stressors were measured through questionnaires about sociopolitical feelings and concerns. Multiple linear regression models examined the relationship between sociopolitical stressors and mental health scores, adjusting for multiple testing. Results: Negative feelings and greater number of sociopolitical concerns were associated with increased pregnancy-related anxiety and depressive symptoms. The most frequently endorsed concern was about issues of racism (72.3%) and women’s rights (62.4%); women endorsing these particular concerns also had higher scores on depression and pregnancy-related anxiety. No significant associations were detected with state anxiety after correction for multiple testing. Limitations: This analysis is cross-sectional and cannot assess causality in the associations between sociopolitical stressors and distress. Conclusions: These results are consistent with the hypothesis that the 2016 election, the subsequent political environment, and the anti-immigrant rhetoric and policies of former President Trump and his administration were sources of stress for Latinos residing in the U.S.

Perturbations to the gut microbiome are implicated in altered neurodevelopmental trajectories that may shape life span risk for emotion dysregulation and affective disorders. However, the sensitive periods during which the microbiome may influence neurodevelopment remain understudied. We investigated relationships between gut microbiome composition across infancy and temperament at 12 months of age. In 67 infants, we examined if gut microbiome composition assessed at 1–3 weeks, 2, 6, and 12 months of age was associated with temperament at age 12 months. Stool samples were sequenced using the 16S Illumina MiSeq platform. Temperament was assessed using the Infant Behavior Questionnaire-Revised (IBQ-R). Beta diversity at age 1–3 weeks was associated with surgency/extraversion at age 12 months. Bifidobacterium and Lachnospiraceae abundance at 1–3 weeks of age was positively associated with surgency/extraversion at age 12 months. Klebsiella abundance at 1–3 weeks was negatively associated with surgency/extraversion at 12 months. Concurrent composition was associated with negative affectivity at 12 months, including a positive association with Ruminococcus-1 and a negative association with Lactobacillus. Our findings support a relationship between gut microbiome composition and infant temperament. While exploratory due to the small sample size, these results point to early and late infancy as sensitive periods during which the gut microbiome may exert effects on neurodevelopment.

Background and objectivesWomen who breastfeed may experience long-term benefits for their health in addition to the more widely appreciated effects on the breastfed child. Breastfeeding may induce long-term effects on biopsychosocial systems implicated in brain health. Also, due to diminished breastfeeding in the postindustrial era, it is important to understand the lifespan implications of breastfeeding for surmising maternal phenotypes in our species’ collective past. Here, we assess how women’s breastfeeding history relates to postmenopausal cognitive performance.MethodologyA convenience sample of Southern California women age 50+ was recruited via two clinical trials, completed a comprehensive neuropsychological test battery and answered a questionnaire about reproductive life history. General linear models examined whether cognitive domain scores were associated with breastfeeding in depressed and non-depressed women, controlling for age, education and ethnicity.ResultsWomen who breastfed exhibited superior performance in the domains of Learning, Delayed Recall, Executive Functioning and Processing Speed compared to women who did not breastfeed (P-values 0.0003–0.015). These four domains remained significant in analyses limited to non-depressed and parous subsets of the cohort. Among those depressed, only Executive Functioning and Processing Speed were positively associated with breastfeeding.Conclusions and implicationsWe add to the growing list of lifespan health correlates of breastfeeding for women’s health, such as the lower risk of type-2 diabetes, cardiovascular disease and breast cancer. We surmise that women’s postmenopausal cognitive competence may have been greater in past environments in which breastfeeding was more prevalent, bolstering the possibility that postmenopausal longevity may have been adaptive across human evolutionary history.Lay SummaryBreastfeeding may affect women’s cognitive performance. Breastfeeding’s biological effects and psychosocial effects, such as improved stress regulation, could exert long-term benefits for the mother’s brain. We found that women who breastfed performed better on a series of cognitive tests in later life compared to women who did not breastfeed.

RATIONALE: The 2016 U.S. presidential election and its aftermath involved political rhetoric and policies that especially targeted women, Latinos, and immigrants. It is possible that concerns about the political environment could affect mental health of individuals in targeted groups. OBJECTIVE: In a cohort of 148 pregnant Latina women, this study investigated how demographics and political concerns related to each other and to maternal anxiety, depression, and perceived stress, which have been associated with adverse birth and child development outcomes. METHODS: In this cross-sectional, self-report study, participants in Southern California completed a one-time questionnaire from January 2017 to May 2018. RESULTS: The highest rates of endorsement were for concerns regarding President Trump’s racism, attitude towards women, and deportation risk for family or friends. From several demographic variables, the only significant predictor of state anxiety was expectant parents’ birthplaces. From several political concerns variables, the only significant predictor of state anxiety was President Trump’s attitude towards women or women’s rights. There were no significant effects on other mental health outcomes. CONCLUSIONS: Results suggest that birthplace and women’s issues may be particularly salient anxiety risk factors for Latina pregnant women in this context. Because of the cross-sectional study design, it is possible that, conversely, pregnant women with high anxiety levels are particularly sensitive to the issue of birthplace or women’s rights. Results imply that the political climate and events in the U.S. could have deleterious consequences that may cascade across generations of Latino Americans via effects on pregnant women.

Background In cooperatively breeding species, individuals may promote their inclusive fitness through allomothering. Humans exhibit some features of cooperative breeding, and previous studies have focused on allomothering by grandparents and juvenile siblings in the postnatal period. We hypothesize that a pregnant woman’s relationships with her siblings (offspring’s maternal aunts and uncles) are beneficial for maternal affect in ways that can enhance the siblings’ inclusive fitness. Maternal affect during pregnancy is a salient target of allocare given the detrimental effects of antepartum mood disorders on birth and infant outcomes. Methodology We test our hypotheses in a cohort of pregnant Latina women in Southern California (N = 201). Predictor variables of interest include number of siblings a participant has, if she has sisters, frequency of seeing siblings, and frequency of communication with siblings. Outcome variables measuring maternal affect include depression, state anxiety, pregnancy-related anxiety and perceived stress. Results Having at least one sister and greater frequency of communication with siblings were associated with fewer depressive symptoms during pregnancy. No significant associations were found between sibling variables and other measures of affect. Conclusion and implications Results suggest that how frequently you communicate with, and not how often you see, siblings could be protective against risk of antepartum depression. Sibling allomothering could impart effects through social–emotional support rather than instrumental support, as a strategy to benefit the prenatal environment in which future nieces and nephews develop. Allomothering may be particularly important in cultural contexts that value family relationships. Future studies should investigate other communities.

The fetal phase of life has long been recognized as a sensitive period of development. Here we posit that pregnancy represents a simultaneous sensitive period for the adult female with broad and persisting consequences for her health and development, including risk for psychopathology. In this review, we examine the transition to motherhood through the lens of developmental psychopathology. Specifically, we summarize the typical and atypical changes in brain and behavior that characterize the perinatal period. We highlight how the exceptional neuroplasticity exhibited by women during this life phase may account for increased vulnerability for psychopathology. Further, we discuss several modes of signaling that are available to the fetus to affect maternal phenotypes (hormones, motor activity, and gene transfer) and also illustrate how evolutionary perspectives can help explain how and why fetal functions may contribute to maternal psychopathology. The developmental psychopathology perspective has spurred advances in understanding risk and resilience for mental health in many domains. As such, it is surprising that this major epoch in the female life span has yet to benefit fully from similar applications.

Acculturation represents an important construct for elucidating the determinants and consequences of health disparities in minority populations. However, the processes and mechanisms underlying acculturation's effects on health are largely undetermined and warrant further study. We integrate concepts from anthropology and statistics to describe the role of sociocultural context as a putative modifier of the relationship between acculturation and health. Sociocultural context may influence the extent to which exposure to host culture leads to internalization of host cultural orientation, and may influence the extent to which acculturation leads to stress and adoption of unhealthy behaviors. We focus on specific aspects of sociocultural context: (1) neighborhood ethno-cultural composition; (2) discrimination; (3) discrepancy between origin and host environments; (4) discrepancy between heritage and host cultures; (5) origin group, host group, and individual attitudes towards assimilation; (6) variation in targets of assimilation within host community; (7) public policy and resources; (8) migration selection bias. We review and synthesize evidence for these moderation effects among first- and later-generation immigrants, refugees, and indigenous populations. Furthermore, we propose best-practices data-collection and statistical-analysis methods for this purpose, in order to improve our understanding of the complex, multilevel aspects of the relationship between acculturation and health.

Microorganisms resident in our bodies participate in a variety of regulatory and pathogenic processes. Here, we describe how etiological pathways implicated in Alzheimer's disease (AD) may be regulated or disturbed by symbiotic microbial activity. Furthermore, the composition of symbiotic microbes has changed dramatically across human history alongside the rise of agriculturalism, industrialization, and globalization. We postulate that each of these lifestyle transitions engendered progressive depletion of microbial diversity and enhancement of virulence, thereby enhancing AD risk pathways. It is likely that the human life span extended into the eighth decade tens of thousands of years ago, yet little is known about premodern geriatric epidemiology. We propose that microbiota of the gut, oral cavity, nasal cavity, and brain may modulate AD pathogenesis, and that changes in the microbial composition of these body regions across history suggest escalation of AD risk. Dysbiosis may promote immunoregulatory dysfunction due to inadequate education of the immune system, chronic inflammation, and epithelial barrier permeability. Subsequently, proinflammatory agents-and occasionally microbes-may infiltrate the brain and promote AD pathogenic processes. APOE genotypes appear to moderate the effect of dysbiosis on AD risk. Elucidating the effect of symbiotic microbiota on AD pathogenesis could contribute to basic and translational research.

Introduction There are sex differences in the prevalence and age-matched incidence of Alzheimer's Disease (AD), with women constituting up to two-thirds of individuals living with AD in the United States. Symptoms of depression and anxiety are also higher in women and can increase dementia risk. Additionally, the decline in estrogen level impacts cognitive function, often leading to difficulties with memory, attention, and concentration. Estrogen withdrawal during menopause also precipitates an increase in depressive symptoms and cognitive decline. Cumulative lifetime estrogen exposure (CLEE), estimated by variables known to influence estrogen levels across the life span, has been correlated with cognitive function later in life. In particular, higher levels of CLEE are associated with improvement in memory performance in older women. Our report is the first to examine how CLEE relates to depression and cognitive function in older women with depression compared to non-depressed controls. Methods A total of 135 participants aged 60 years and older were included in the analysis. Sixty-four clinically depressed women (mean age 69.1 (SD 6.4) years) were compared to 71 non-depressed age-matched controls (mean age 66.1 (SD 8.3) years) using a lifetime estrogen exposure questionnaire. Depressed participants were included with the 24-item Hamilton Rating Scale for Depression (HAMD) score of > 14 at baseline. CLEE was defined by combining the reproductive span (age of menopause minus age of menarche) and any post-menopausal hormone replacement therapy use. Participants were divided into higher versus lower CLEE groups based on a median of 480 months of estrogen exposure. Participants completed a comprehensive neuropsychological test battery that evaluated learning (California Verbal Learning Test-II [Trial 1 through 5 Total] or Hopkins Verbal Learning Test [Total Recall], Rey–Osterrieth Complex Figure Test [3-minute recall]); delayed recall (California Verbal Learning Test-II [long delayed free recall] or Hopkins Verbal Learning Test [Delayed Recall], Rey–Osterrieth Complex Figure Test [30-minute delayed recall]); and executive functioning (Trail Making Test B, Controlled Oral Word Association test [FAS]).We transformed raw scores to z-scores for each test score for each participant. Z-scores were reversed when necessary so that high z-scores represented good performance for all measures. These z-scores were averaged within each neuropsychological domain to produce composite scores.General linear models were used to examine whether cognitive domain scores were associated with CLEE in depressed and non-depressed women, controlling for age, educational level and ethnicity. Results Depressed and non-depressed women had significantly different levels of CLEE: 448.6 (SD 66.0) vs. 487.3 (SD 108.6), t(133) = 2.52, p = .01. CLEE was not associated with cognitive performance in the combined sample of depressed and non-depressed participants, controlling for depression status. However, amongst non-depressed participants, higher CLEE group was significantly associated with better performance on delayed recall (F(1,60) = 5.45, p=0.02; effect size = .64). Conclusions Consistent with previous findings, higher CLEE was associated with better performance on delayed recall, though we found this effect only among non-depressed participants. This suggests an enduring protective role of estrogen on memory in non-depressed older postmenopausal women. CLEE was not associated with cognitive function in older women with depression. Further research should examine the role of the CLEE in older women in depression, treatment response and in cognitive decline. Funding K24 AT009198 R01 AT008383 (NCCIH) R01 AT008383-04S (NCCIH)

Background: Hispanic Americans consistently exhibit an intergenerational increase in the prevalence of many noncommunicable chronic physical and mental disorders. Methods: We review and synthesize evidence suggesting that a constellation of prenatal and postnatal factors may play crucial roles in explaining this trend. We draw from relevant literature across several disciplines, including epidemiology, anthropology, psychology, medicine (obstetrics, neonatology), and developmental biology. Results: Our resulting model is based on evidence that among women, the process of postmigration cultural adjustment (i.e., acculturation) is associated, during pregnancy and after delivery, with psychological and behavioral states that can affect offspring development in ways that may alter susceptibility to noncommunicable chronic disease risk in subsequent-generation Hispanic Americans. We propose one integrated process model that specifies the biological, behavioral, psychological, and sociocultural pathways by which maternal acculturation may influence the child's long-term health. We synthesize evidence from previous studies to describe how acculturation among Hispanic American mothers is associated with alterations to the same biobehavioral systems known to participate in the processes of prenatal and postnatal developmental programming of disease risk. In this manner, we focus on the concepts of biological and cultural mother-to-child transmission across the prenatal and postnatal life phases. We critique and draw from previous hypotheses that have sought to explain this phenomenon (of declining health across generations). We offer recommendations for examining the transgenerational effects of acculturation. Conclusion: A life course model with a greater focus on maternal health and well-being may be key to understanding transgenerational epidemiological trends in minority populations, and interventions that promote women's wellness may contribute to the elimination or reduction of health disparities.

Evolution by natural selection eliminates maladaptive traits from a species, and yet Alzheimer’s Disease (AD) persists with rapidly increasing prevalence globally. This apparent paradox begs an explanation within the framework of evolutionary sciences. Here, I summarize and critique previously proposed theories to explain human susceptibility to AD, grouped into 8 distinct hypotheses based on the concepts of novel extension of the lifespan; lack of selective pressure during the post-reproductive phase; antagonistic pleiotropy; rapid brain evolution; delayed neuropathy by selection for grandmothering; novel alleles selected to delay neuropathy; by-product of selection against cardiovascular disease; and thrifty genotype. Subsequently, I describe a new hypothesis inspired by the concept of mismatched environments. Many of the factors that enhance AD risk today may have been absent or functioned differently before the modern era, potentially making AD a less common affliction for age-matched individuals before industrialization and for the majority of human history. Future research is needed to further explore whether changes in environments and lifestyles across human history moderate risk factors and susceptibility to AD.

Author(s): Fox, Molly; Sandman, Curt A; Davis, Elysia Poggi; Glynn, Laura M | Abstract: BACKGROUND:An issue of critical importance for psychiatry and women's health is whether postpartum depression (PPD) represents a unique condition. The Diagnostic and Statistical Manual of Mental Disorders asserts that major depressive disorder (MDD) may present with peripartum onset, without suggesting any other differences between MDD and PPD. The absence of any distinct features calls into question the nosologic validity of PPD as a diagnostic category. The present study investigates whether symptom profiles differ between PPD and depression occurring outside the postpartum phase. METHODS:In a prospective, longitudinal study of parturient women (Nn=n239), we examine the manifestation of depression symptoms. We assess factor structure of symptom profiles, and whether factors are differentially pronounced during and after the postpartum period. RESULTS:Factors were revealed representing: Worry, Emotional/Circadian/Energetic Dysregulation, Somatic/Cognitive, Appetite, Distress Display, and Anger symptoms. The factor structure was validated at postpartum and after-postpartum timepoints. Interestingly, the Worry factor, comprising anxiety and guilt, was significantly more pronounced during the postpartum timepoint, and the Emotional/Circadian/Energetic Dysregulation factor, which contained sadness and anhedonia, was significantly less pronounced during the postpartum period. CONCLUSIONS:These results suggest that PPD may be a unique syndrome, necessitating research, diagnosis, and treatment strategies distinct from those for MDD. Results indicate the possibility that Worry is an enhanced feature of PPD compared to depression outside the postpartum period, and the crucial role of sadness/anhedonia in MDD diagnosis may be less applicable to PPD diagnosis.

It is yet unknown how similar women's hormone levels are during successive pregnancies, and very little is known about the degree to which siblings experience similar prenatal environments. Given the importance of understanding how women's reproductive life histories exert cumulative effects on health via hormone exposure, and the importance of understanding how fetal programming via endocrine signaling affects sibling trait concordance, here, we address this important lacuna in the literature.This study aimed to investigate how consistent women's hormone profiles are across two successive pregnancies.This longitudinal, prospective study followed a cohort of 28 women across two pregnancies (PREG 1 and PREG 2). Women's circulating hormone levels were assessed from blood samples at 25, 31, and 37 weeks' gestation for adrenocorticotropic hormone (ACTH), placental corticotropin-releasing hormone (pCRH), cortisol, estradiol, and progesterone. ACTH and cortisol levels were assessed 3 months postpartum. Research questions include: Are hormone levels in PREG 2 significantly different from levels in PREG 1? What proportion of variance in PREG 2 hormone levels is attributable to variance in PREG 1 levels? Are hormone levels more stable between PREG 1 and PREG 2 compared with postpartum phases following these pregnancies? Is pCRH, which is completely placentally derived, less similar than other hormones across successive pregnancies?Pregnant women attended study visits at a university psychobiology laboratory in Southern California.Comparisons of hormone concentrations across women's successive pregnancies via paired t test revealed substantial consistency from one pregnancy to another, with only significant differences between pregnancies for pCRH. Regressions revealed substantial predictability from one pregnancy to another, with between 17-56% of PREG 2 variances accounted for by PREG 1 values. Women exhibited lower degrees of consistency and predictability in hormone levels across postpartum phases compared with gestational concentrations. This is the first study to describe maternal and placental hormone levels across successive pregnancies.

Acculturation represents an important construct for elucidating the determinants and consequences of health disparities in minority populations. However, the processes and mechanisms underlying acculturation’s effects on health are largely undetermined and warrant further study. We integrate concepts from anthropology and statistics to describe the role of sociocultural context as a putative modifier of the relationship between acculturation and health. Sociocultural context may influence the extent to which exposure to host culture leads to internalization of host cultural orientation, and may influence the extent to which acculturation leads to stress and adoption of unhealthy behaviors. We focus on specific aspects of sociocultural context: (1) neighborhood ethno-cultural composition; (2) discrimination; (3) discrepancy between origin and host environments; (4) discrepancy between heritage and host cultures; (5) origin group, host group, and individual attitudes towards assimilation; (6) variation in targets of assimilation within host community; (7) public policy and resources; (8) migration selection bias. We review and synthesize evidence for these moderation effects among first- and later-generation immigrants, refugees, and indigenous populations. Furthermore, we propose best-practices data-collection and statistical-analysis methods for this purpose, in order to improve our understanding of the complex, multilevel aspects of the relationship between acculturation and health.

The effect of estrogen on Alzheimer's Disease (AD) risk has received substantial research and media attention, especially in terms of hormone replacement therapy. But reproductive history is also an important modifier of estrogenic exposure, and deserves further investigation. Importantly, there is wide variation in reproductive patterns that modifies estrogen exposure during the reproductive span, which previous AD studies have not incorporated into their calculations. We measured degree of Alzheimer's-type dementia in a cohort of elderly British women, and collected detailed reproductive and medical history information, which we used to estimate number of months with estrogen exposure and number of months with menstrual cycles. Using Cox proportional-hazards models, we find that longer duration of estrogen exposure may have a protective effect against AD risk, such that for every additional month with estrogen, women experienced on average a 0.5% decrease in AD risk (N=89, p=0.02). More menstrual cycles may also have a protective effect against AD risk, although this result was of borderline statistical significance (p0.10). These results build upon previous methodologies by taking into account a variety of parameters including oral contraceptive use, breastfeeding, post-partum anovulation, abortions, and miscarriages. Additionally, Cox models revealed that longer reproductive span, age21 at first birth, and more months in lifetime spent pregnant had protective effects against AD risk.

The effect of early and midlife factors on later-life cognitive function has attracted scientific and public interest in recent years, especially with respect to hormonal risk factors for dementia. There is substantial evidence for reproductive history affecting Alzheimer's disease (AD) etiology. Here, we demonstrate how breastfeeding history affects women's risk of AD. Reproductive history data was collected, and AD diagnostic interviews were performed, for a cohort of elderly British women. Using Cox proportional-hazard models, we find that longer breastfeeding duration corresponded to reduced risk of AD (p < 0.01, n = 81). Women who breastfed had lower AD risk than women who did not breastfeed (p = 0.017, n = 81). Breastfeeding practices are an important modifier of cumulative endogenous hormone exposure for mothers. Ovarian hormone deprivation and/or insulin sensitivity benefits of breastfeeding may be responsible for the observed reduction in AD risk. Future studies concerning hormone effects on AD risk should consider how reproductive history leads to variation in endogenous hormone exposure and how this may influence the relationship between hormones and AD.

Background and objectives: Alzheimer’s disease (AD) shares certain etiological features with autoimmunity. Prevalence of autoimmunity varies between populations in accordance with variation in environmental microbial diversity. Exposure to microorganisms may improve individuals’ immunoregulation in ways that protect against autoimmunity, and we suggest that this may also be the case for AD. Here, we investigate whether differences in microbial diversity can explain patterns of age-adjusted AD rates between countries. Methodology: We use regression models to test whether pathogen prevalence, as a proxy for microbial diversity, across 192 countries can explain a significant amount of the variation in age-standardized AD disability-adjusted life-year (DALY) rates. We also review and assess the relationship between pathogen prevalence and AD rates in different world populations. Results: Based on our analyses, it appears that hygiene is positively associated with AD risk. Countries with greater degree of sanitation and lower degree of pathogen prevalence have higher age-adjusted AD DALY rates. Countries with greater degree of urbanization and wealth exhibit higher age-adjusted AD DALY rates. Conclusions and implications: Variation in hygiene may partly explain global patterns in AD rates. Microorganism exposure may be inversely related to AD risk. These results may help predict AD burden in developing countries where microbial diversity is rapidly diminishing. Epidemiological forecasting is important for preparing for future healthcare needs and research prioritization.

Acculturation represents an important construct in the context of health disparities. Although several studies have reported relationships between various aspects of acculturation and health in minority populations, crucial inconsistencies remain. One likely reason for these inconsistencies may relate to limitations in the conceptualization and operationalization of acculturation, particularly in the context of health research. The acculturation construct underwent major conceptual and operational change when it was adapted from anthropology to psychology, and we argue another major shift is now required for use of this construct in health research. Issues include determining whether acculturation measures should focus on an individual's internal attitudes or overt behaviors; whether they should characterize cultural orientation status at a given point in time or change over time; whether measures should be culture-specific or more global in nature; how the issue of multiculturalism should be addressed; how measures can optimally incorporate multiple dimensions of acculturation; and whether proxy measures should be used. These issues are important in the context of health research because of their implications for determining the direct and indirect effects of cultural change on health-related biological and behavioral processes. We elaborate on and address each of these issues from a perspective that spans multiple disciplines across the biological and social sciences, and offer concrete recommendations with the ultimate goal of achieving a better understanding of the role of acculturation in minority health and health disparities.

Because only daughters inherit the paternal X-chromosome, an asymmetry in adaptive investment decisions has been suggested for certain patrilineal kin. Namely, paternal grandmothers (PGMs) may favor a granddaughter over a grandson, because (within the limits of paternity uncertainty) the former definitely carries one of their X-chromosomes, while the latter definitely does not. Here, we test the hypothesis that the PGMs' sex-specific favoritism influences reproductive scheduling. Using family-reconstitution data, we analyzed interbirth intervals (IBIs) in the historical population from the Krummhorn (Ostfriesland, Germany). In order to account for potentially timevarying effects on IBIs we applied (and combined) both the additive hazards regression of Aalen and the Cox proportional hazards model. We found that the presence of the PGM but not that of the maternal grandmother (MGM), correlates with the IBI following the birth of a grandchild as a function of the grandchild's sex. Specifically, in the presence of a PGM, the IBIs following the birth of a granddaughter are longer than in her absence. However, contrary to predictions from theoretical life history framework, model estimates for a PGM's effect on a mother's IBI did not significantly vary over time This study supports the hypothesis that PGM behavior differs according to her grandchild's sex. Further research should now explore the biological mechanism underlying this phenomenon.

Biologists use genetic relatedness between family members to explain the evolution of many behavioural and developmental traits in humans, including altruism, kin investment and longevity. Women's post-menopausal longevity in particular is linked to genetic relatedness between family members. According to the ‘grandmother hypothesis’, post-menopausal women can increase their genetic contribution to future generations by increasing the survivorship of their grandchildren. While some demographic studies have found evidence for this, others have found little support for it. Here, we re-model the predictions of the grandmother hypothesis by examining the genetic relatedness between grandmothers and grandchildren. We use this new model to re-evaluate the grandmother effect in seven previously studied human populations. Boys and girls differ in the per cent of genes they share with maternal versus paternal grandmothers because of differences in X-chromosome inheritance. Here, we demonstrate a relationship between X-chromosome inheritance and grandchild mortality in the presence of a grandmother. With this sex-specific and X-chromosome approach to interpreting mortality rates, we provide a new perspective on the prevailing theory for the evolution of human female longevity. This approach yields more consistent support for the grandmother hypothesis, and has implications for the study of human evolution.

We propose a transdisciplinary, life span framework for examining the underlying cause of the observed intergenerational decline in health among Hispanic Americans. We focus on acculturation, and we posit that acculturation-related processes in first-generation Hispanic immigrant mothers may affect the intrauterine development of an unborn child, via the process of fetal programming, to produce phenotypic effects that may alter the susceptibility for noncommunicable chronic diseases. In this manner, an intergenerational cascade of perpetuation may become established. Our framework may shed light on the biological, behavioral, and social causes of intergenerational cycles of vulnerability among immigrant minority groups, with public health and policy implications for primary prevention and intervention.

People living in sanitized environments may be at greater Alzheimer's risk. We compare Alzheimer's rates in different countries in light of countries' historical and contemporary pathogen prevalence, sanitation, and urbanization. We find that countries that are less urbanized, with more pathogens and lower degree of sanitation have lower Alzheimer's rates., Background and objectives: Alzheimer’s disease (AD) shares certain etiological features with autoimmunity. Prevalence of autoimmunity varies between populations in accordance with variation in environmental microbial diversity. Exposure to microorganisms may improve individuals’ immunoregulation in ways that protect against autoimmunity, and we suggest that this may also be the case for AD. Here, we investigate whether differences in microbial diversity can explain patterns of age-adjusted AD rates between countries. Methodology: We use regression models to test whether pathogen prevalence, as a proxy for microbial diversity, across 192 countries can explain a significant amount of the variation in age-standardized AD disability-adjusted life-year (DALY) rates. We also review and assess the relationship between pathogen prevalence and AD rates in different world populations. Results: Based on our analyses, it appears that hygiene is positively associated with AD risk. Countries with greater degree of sanitation and lower degree of pathogen prevalence have higher age-adjusted AD DALY rates. Countries with greater degree of urbanization and wealth exhibit higher age-adjusted AD DALY rates. Conclusions and implications: Variation in hygiene may partly explain global patterns in AD rates. Microorganism exposure may be inversely related to AD risk. These results may help predict AD burden in developing countries where microbial diversity is rapidly diminishing. Epidemiological forecasting is important for preparing for future healthcare needs and research prioritization.

The role of serotonin in depression and antidepressant treatment remains unresolved despite decades of research. In this paper, we make three major claims. First, serotonin transmission is elevated in multiple depressive phenotypes, including melancholia, a subtype associated with sustained cognition. The primary challenge to this first claim is that the direct pharmacological effect of most symptom-reducing medications, such as the selective serotonin reuptake inhibitors (SSRIs), is to increase synaptic serotonin. The second claim, which is crucial to resolving this paradox, is that the serotonergic system evolved to regulate energy. By increasing extracellular serotonin, SSRIs disrupt energy homeostasis and often worsen symptoms during acute treatment. Our third claim is that symptom reduction is not achieved by the direct pharmacological properties of SSRIs, but by the brain's compensatory responses that attempt to restore energy homeostasis. These responses take several weeks to develop, which explains why SSRIs have a therapeutic delay. We demonstrate the utility of our claims by examining what happens in animal models of melancholia and during acute and chronic SSRI treatment.

When considering inclusive fitness, it is expected that individuals will provide more care towards those with whom they are more closely related. Thus, if a selfish X-linked genetic element influenced care giving, we would expect care giving to vary with X-relatedness. Recent studies have shown that X-chromosome inheritance patterns may influence selection of traits affecting behavior and life-history. Sexually antagonistic (SA) zygotic drive could encourage individuals to help those with whom they are more likely to share genetic material at the expense of other relatives. We reanalyze previously reported data in light of this new idea. We also evaluate the effects of paternity uncertainty on SA-zygotic drive. Our evidence suggests that human paternal discrepancy is relatively low. Using published models, we find the effects of paternal discrepancy do not override opportunity for selection based on X-relatedness. Based on these results, longevity and grandmothering behaviors, including favoritism, may be more heavily influenced by selection on the X-chromosome than by paternity uncertainty.