Cumulative adversity and survival in the wild.

Protecting populations contending with co-occurring stressors requires a better understanding of how multiple early-life stressors affect the fitness of natural systems. However, the complexity of such research has limited its advancement and prevented us from answering new questions. In human studies, cumulative risk models predict adult health risk based on early adversity exposure. We apply a similar framework in wild yellow-bellied marmots (Marmota flaviventer). We tested cumulative adversity indices (CAIs) across different adversity types and time windows. All CAIs were associated with decreased pup survival and were well supported. Moderate and acute, but not standardized CAIs were associated with decreased lifespan, supporting the cumulative stress hypothesis and the endurance of early adversity. Multivariate models showed that differences in lifespan were driven by weaning date, precipitation, and maternal loss, but they performed poorly compared with CAI models. We highlight the development, utility, and insights of CAI approaches for ecology and conservation.

Cranial fluctuating asymmetry and its relationship with non-specific physiological stress indicators in a contemporary South African cadaveric skeletal sample.

OBJECTIVES: Biological anthropologists frequently explore skeletal asymmetry, together with population health and disease. Given the conflicting findings in existing literature, this study aimed to clarify whether an association exists in a South African sample. MATERIALS: Dry bone and cranial micro-focus X-ray Computed Tomography (micro-XCT) scans of 115 South African individuals were assessed. METHODS: Fluctuating asymmetry (FA) indices were calculated from interlandmark distances, and the frequency of four types of non-specific signs of physiological stress were documented to explore the relationship between FA and disease. RESULTS: Black South Africans did not exhibit a high FA index; however, they had the highest prevalence of non-specific signs of physiological stress. However, no significant correlations were detected between FA indices and pathological lesions. CONCLUSION: No correlation was observed between FA and populations from different socio-economic backgrounds. However, individuals of lower socio-economic status (SES) demonstrated a greater prevalence of non-specific signs of physiological stress. SIGNIFICANCE: This research suggests that skeletal indicators of stress may be a suitable biological marker for assessing differences in SES among population groups, while indicating that levels of cranial FA is an inadequate biological marker. LIMITATIONS: Possible limitations may include measurement error, and the lack of information on the life history and medical records of individuals in this sample. SUGGESTIONS FOR FURTHER RESEARCH: Future research should include a larger sample with more South African groups, and should evaluate the potential association among age, FA, and expression of skeletal markers of disease.

Parental developmental experience affects vocal learning in offspring.

Cultural and genetic inheritance combine to enable rapid changes in trait expression, but their relative importance in determining trait expression across generations is not clear. Birdsong is a socially learned cognitive trait that is subject to both cultural and genetic inheritance, as well as being affected by early developmental conditions. We sought to test whether early-life conditions in one generation can affect song acquisition in the next generation. We exposed one generation (F1) of nestlings to elevated corticosterone (CORT) levels, allowed them to breed freely as adults, and quantified their son's (F2) ability to copy the song of their social father. We also quantified the neurogenetic response to song playback through immediate early gene (IEG) expression in the auditory forebrain. F2 males with only one corticosterone-treated parent copied their social father's song less accurately than males with two control parents. Expression of ARC in caudomedial nidopallium (NCM) correlated with father-son song similarity, and patterns of expression levels of several IEGs in caudomedial mesopallium (CMM) in response to father song playback differed between control F2 sons and those with a CORT-treated father only. This is the first study to demonstrate that developmental conditions can affect social learning and neurogenetic responses in a subsequent generation.

Early-Life Silver Spoon Improves Survival and Breeding Performance of Adult Zebra Finches.

AbstractDevelopmental plasticity allows organisms to increase the fit between their phenotype and their early-life environment. The extent to which such plasticity also enhances adult fitness is not well understood, however, particularly when early-life and adult environments differ substantially. Using a cross-factorial design that manipulated diet at two life stages, we examined predictions of major hypotheses-silver spoon, environmental matching, and thrifty phenotype-concerning the joint impacts of early-life and adult diets on adult morphology/display traits, survival, and reproductive allocation. Overall, results aligned with the silver spoon hypothesis, which makes several predictions based on the premise that development in poor-quality environments constrains adult performance. Males reared and bred on a low-protein diet had lower adult survivorship than other male treatment groups; females' survivorship was higher than males' and not impacted by early diet. Measures of allocation to reproduction primarily reflected breeding diet, but where natal diet impacted reproduction, results supported the silver spoon. Both sexes showed reduced expression of display traits when reared on a low-protein diet. Results accord with other studies in supporting the relevance of the silver spoon hypothesis to birds and point to significant ramifications of sex differences in early-life viability selection on the applicability/strength of silver spoon effects.

Effects of inbreeding and elevated rearing temperatures on strategic sperm investment.

Males often strategically adjust the number of available sperm based on the social context (i.e. sperm priming response), but it remains unclear how environmental and genetic factors shape this adjustment. In freshwater ecosystems, high ambient temperatures often lead to isolated pools of hotter water in which inbreeding occurs. Higher water temperatures and inbreeding can impair fish development, potentially disrupting sperm production. We used guppies (Poecilia reticulata) to investigate how developmental temperature (26 °C, 30 °C) and male inbreeding status (inbred, outbred) influence their sperm priming response. We also tested if sperm priming was affected by whether the female was a relative (sister) and whether she was inbred or outbred. There was no effect of rearing temperature; male inbreeding status alone determined the number of available sperm in response to female presence, her inbreeding status, and her relatedness. Inbred males produced significantly more sperm in the presence of an unrelated, outbred female than when no female was present. Conversely, outbred males did not alter the number of sperm available in response to female presence or relatedness. Moreover, inbred males produced marginally more sperm when exposed to an unrelated female that was outbred rather than inbred, but there was no difference when exposed to an inbred female that was unrelated versus related. Together, a sperm priming response was only observed in inbred males when exposed to an outbred female. Outbred females in our study were larger than inbred females, suggesting that inbred males strategically allocated ejaculate resources toward females in better condition.

Long-term effects of Preweaning environmental impoverishment on neurobehavioral and neurocognitive outcomes in Sprague Dawley rats: An early environmental stress model.

Developmental stress, including low socioeconomic status (SES), can induce dysregulation of the hypothalamic-pituitary-adrenal axis and result in long-term changes in stress reactivity. Children in lower SES conditions often experience more stress than those in other SES groups. There are multiple model systems of early environmental stress (EES), one of which is reduced cage bedding. Here we tested the effects of both prenatal and lactational EES in rats on a range of long-term behavioral and cognitive outcomes. There were persistent reductions in body weight in the EES rats in both sexes. The behavioral results showed no effects on learning and memory using tests of spatial learning or cognitive flexibility in the Morris water maze, egocentric learning in the Cincinnati water maze, or working memory in the radial-arm maze. There were no effects on basic open-field activity, elevated zero-maze, or forced swim test, but EES rats had reduced time in the dark side of the light/dark test. When rats were drug challenged in the open-field with d-amphetamine or MK-801, there were no differential responses to d-amphetamine, but the EES group under responded compared with the drug-induced hyperactivity in the control group in both males and females. The objective was to establish a developmental stress model that induced cognitive deficits and to the extent that this method did not cause such effects it was not the model we sought. However, the data showed several long-term effects of EES, including the reduced response to the irreversible NMDA antagonist MK-801. This effect merits further investigation.

Linear enamel hypoplasia in Homo naledi reappraised in light of new Retzius periodicities.

OBJECTIVES: Among low-latitude apes, developmental defects of enamel often recur twice yearly, linkable to environmental cycles. Surprisingly, teeth of Homo naledi from Rising Star in South Africa (241-335 kya), a higher latitude site with today a single rainy season, also exhibit bimodally distributed hypoplastic enamel defects, but with uncertain timing and etiology. Newly determined Retzius periodicities for enamel formation in this taxon enable a reconstruction of the temporal patterning of childhood stress. METHODS: Using high resolution casts of 31 isolated anterior teeth from H. naledi, 82 enamel defects (linear enamel hypoplasia [LEH]) were identified. Seventeen teeth are assigned to three individuals. Perikymata in the occlusal wall of enamel furrows and between the onsets of successive LEH were visualized with scanning electron microscopy and counted. Defects were measured with an optical scanner. Conversion of perikymata counts to estimates of LEH duration and inter-LEH interval draws upon Retzius periodicities of 9 and 11 days. RESULTS: Anterior teeth record more than a year of developmental distress, expressed as two asymmetric intervals centered on 4.5 and 7.5 months bounded by three LEH. Durations, also, show bimodal distributions, lasting 3 or 12 weeks. Short duration LEH are more severe than long duration. Relative incisor/canine rates of formation are indistinguishable from modern humans. DISCUSSION: We invoke a disease and dearth model, with short episodes of distress reflecting onset of disease in young infants, lasting about 3 weeks, followed by a season of undernutrition, possibly intensified by secondary plant compounds, spanning about 12 weeks, inferably coincident with austral winter.

Oral disease is linked to low nestling condition and brood size in a raptor species living in a highly modified environment.

Anthropogenic stressors can favor the occurrence of noninfectious disease that can be worsened by the impact of opportunistic pathogens, making the epizootiology of environmental diseases difficult to unravel. The incidence and impact of oral lesions in nestlings of a facultative scavenger species, the black kite Milvus migrans, were examined over seven breeding seasons in the highly degraded environment close to Madrid, Spain. We found an overall prevalence of 31% of nestlings with oral lesions, with no clear spatial pattern in nests with affected and unaffected individuals. The occurrence and number of oral lesions were negatively associated with nestling body condition and brood size. Broods, where all siblings had oral lesions, were smaller than those where some or all siblings were apparently healthy, suggesting that oral disease could be causing nestling mortality and, consequently, brood size reduction. In turn, nestling body condition was negatively affected by lesion occurrence, brood size, and laying date. Although these relationships were bidirectional, piecewise structural equation modeling analyses showed a greater negative effect of body condition on lesion occurrence than vice versa, indicating that nestlings in poorer body condition were more likely to develop oral lesions (which could contribute to aggravate their state of deterioration) than those in better condition. Nestlings from small broods were also more likely to have oral disease (directly or indirectly through their lower body condition) than nestlings from large broods. Nestlings that hatched last in the broods showed greater development stress than those that hatched first. Anthropogenic stressors could trigger poor body condition, and contribute to microbiota dysbiosis-related diseases. Although further research is needed to determine the consequences for the long-term fitness of individuals, actions should be taken to mitigate adverse conditions that may favor the appearance of environmental diseases associated with peri-urban areas, given their rapid expansion over natural areas.

Emotional and sensory dysregulation as a possible missing link in attention deficit hyperactivity disorder: A review.

Attention Deficit Hyperactivity Disorder (ADHD) is a common developmental disorder affecting 5-7% of adults and children. We surveyed the literature to examine ADHD through three pillars: developmental characteristics, symptomatology, and treatment strategies. Firstly, in terms of developmental characterstics, early life stress may increase the risk of developing ADHD symptoms according to animal models' research. Secondly, the current core symptoms of ADHD are comprised of inattention, hyperactivity, and impulsivity. However, the up-to-date literature indicates individuals with ADHD experience emotional and sensory dysregulation as well, which early-life stress may also increase the risk of. Finally, we discuss the therapeutic benefits of methylphenidate on both the current core ADHD symptoms and the sensory and emotional dysregulation found in those with ADHD. In summation, we surveyed the recent literature to analyze (i) the potential role of early-life stress in ADHD development, (ii) the involvement of emotional and sensory dysregulation in ADHD symptomatology and finally, (iii) the therapeutic intervention with methylphenidate, aiming to reduce the potential effect of early life stress in ADHD, and mainly emotional and sensory dysregulation. The apparent but currently less recognized additional symptoms of emotional and sensory dysregulation in ADHD call for further investigation of these possible causes and thus increasing treatments efficacy in individuals with ADHD.

Enduring effects of early-life adversity on reward processes: A systematic review and meta-analysis of animal studies.

Two-thirds of individuals experience adversity during childhood such as neglect, abuse or highly-stressful events. Early-life adversity (ELA) increases the life-long risk of developing mood and substance use disorders. Reward-related deficits has emerged as a key endophenotype of such psychiatric disorders. Animal models are invaluable for studying how ELA leads to reward deficits. However, the existing literature is heterogenous with difficult to reconcile findings. To create an overview, we conducted a systematic review containing multiple meta-analyses regarding the effects of ELA on reward processes overall and on specific aspects of reward processing in animal models. A comprehensive search identified 120 studies. Most studies omitted key details resulting in unclear risk of bias. Overall meta-analysis showed that ELA significantly reduced reward behaviors (SMD: -0.42 [-0.60; -0.24]). The magnitude of ELA effects significantly increased with longer exposure. When reward domains were analyzed separately, ELA only significantly dampened reward responsiveness (SMD: -0.525[-0.786; -0.264]) and social reward processing (SMD: -0.374 [-0.663; -0.084]), suggesting that ELA might lead to deficits in specific reward domains.

Effects of developmental and adult environments on ageing.

Developmental and adult environments can interact in complex ways to influence the fitness of individuals. Most studies investigating effects of the environment on fitness focus on environments experienced and traits expressed at a single point in an organism's life. However, environments vary with time, so the effects of the environments that organisms experience at different ages may interact to affect how traits change throughout life. Here, we test whether thermal stress experienced during development leads individuals to cope better with thermal stress as adults. We manipulated temperature during both development and adulthood and measured a range of life-history traits, including senescence, in male and female seed beetles (Callosobruchus maculatus). We found that thermal stress during development reduced adult reproductive performance of females. In contrast, life span and age-dependent mortality were affected more by adult than developmental environments, with high adult temperatures decreasing longevity and increasing age-dependent mortality. Aside from an interaction between developmental and adult environments to affect age-dependent changes in male weight, we did not find any evidence of a beneficial acclimation response to developmental thermal stress. Overall, our results show that effects of developmental and adult environments can be both sex and trait specific, and that a full understanding of how environments interact to affect fitness and ageing requires the integrated study of conditions experienced during different stages of ontogeny.

Infectious disease and cognition in wild populations.

Infectious disease is linked to impaired cognition across a breadth of host taxa and cognitive abilities, potentially contributing to variation in cognitive performance within and among populations. Impaired cognitive performance can stem from direct damage by the parasite, the host immune response, or lost opportunities for learning. Moreover, cognitive impairment could be compounded by factors that simultaneously increase infection risk and impair cognition directly, such as stress and malnutrition. As highlighted in this review, however, answers to fundamental questions remain unresolved, including the frequency, duration, and fitness consequences of infection-linked cognitive impairment in wild animal populations, the cognitive abilities most likely to be affected, and the potential for adaptive evolution of cognition in response to accelerating emergence of infectious disease.

Heightened among-individual variation in life history but not morphology is related to developmental temperature in reptiles.

Increases in phenotypic variation under extreme (e.g. novel or stressful) environmental conditions are emerging as a crucial process through which evolutionary adaptation can occur. Lack of prior stabilizing selection, as well as potential instability of developmental processes in these environments, may lead to a release of phenotypic variation that can have important evolutionary consequences. Although such patterns have been shown in model study organisms, we know little about the generality of trait variance across environments for non-model organisms. Here, we test whether extreme developmental temperatures increase the phenotypic variation across diverse reptile taxa. We find that the among-individual variation in a key life-history trait (post-hatching growth) increases at extreme cold and hot temperatures. However, variations in two measures of hatchling morphology and in hatchling performance were not related to developmental temperature. Although extreme developmental temperatures may increase the variation in growth, our results suggest that plastic responses to stressful incubation conditions do not generally make more extreme phenotypes available to selection. We discuss the reasons for the general lack of increased variability at extreme incubation temperatures and the implications this has for local adaptation in hatchling morphology and physiology.

Developmental conditions have intergenerational effects on corticosterone levels in a passerine.

The developmental environment can have powerful, canalizing effects that last throughout an animal's life and even across generations. Intergenerational effects of early-life conditions may affect offspring phenotype through changes in the hypothalamic-pituitary-adrenal axis (HPA). However, such effects remain largely untested in altricial birds. Here, we tested the impact of maternal and paternal developmental conditions on offspring physiology and morphology in the zebra finch (Taeniopygia guttata). Specifically, we exposed one generation (F1) to elevated corticosterone (CORT) during development and quantified the impact on offspring (F2) phenotype. We predicted that intergenerational effects would be apparent through effects of parental developmental treatment on offspring body mass, growth, body condition, body composition, and CORT levels. We found an intergenerational impact on CORT levels, such that F2 birds reared by CORT-treated fathers had higher baseline CORT than F2 birds reared by control fathers. This result shows the potential for intergenerational effects on endocrine function, resulting from developmental conditions. We found no effect of parental treatment on F2 body mass, size, or body condition, but we found that the body mass and tarsus length for offspring and parent were correlated. Our study demonstrates the subtle effects of developmental conditions across generations and highlights the importance of distinguishing between maternal and paternal effects when studying intergenerational effects, especially for species with biparental care.

Impact of preweaning stress on long-term neurobehavioral outcomes in Sprague-Dawley rats: Differential effects of barren cage rearing, pup isolation, and the combination.

Two developmental stressors were compared in preweaning rats exposed to either one stressor or both. Stressors were barren cage rearing or maternal separation (pup isolation). 40 gravid Sprague-Dawley CD/IGS rats were randomly assigned to two cage conditions: standard (Std) cage or barren cage (Bar), 20 litters/condition throughout gestation and lactation. After delivery, litters were randomly culled to 4 males and 4 females. The second stressor was maternal separation: Two male/female pairs per litter were isolated from their dam 4 h/day (Iso) and two pairs were not (Norm). Hence, there were 4 conditions: Std-Norm, Std-Iso, Bar-Norm, and Bar-Iso. One pair/litter/stress condition received the following: elevated zero-maze (EZM), open-field, swim channel, Cincinnati water maze, conditioned fear, and open-field with methamphetamine challenge. The second pair/litter/condition received the light-dark test, swim channel, Morris water maze, forced swim, and EZM with diazepam challenge. Barren rearing reduced EZM time-in-open, whereas isolation rearing reduced open-field activity in males and increased it in females. Effects on straight channel swimming were minor. In the Cincinnati water maze test of egocentric learning, isolation rearing increased errors whereas barren cage housing reduced errors in combination with normal rearing. Barren cage with maternal separation (pup isolation) increased Cincinnati water maze escape latency but not errors. Barren cage housing reduced hyperactivity in response to methamphetamine. Isolation rearing increased time in open in the EZM after diazepam challenge. Trends were seen in the Morris water maze. These suggested that barren cage and isolation rearing in combination reduced latency on acquisition on days 1 and 2 in males, whereas females had increased latency on days 2 and 3. Combined exposure to two developmental stressors did not induce additive or synergistic effects, however the data show that these stressors had long-term effects with some evidence that the combination of both caused effects when either stressor alone did not, but synergism was not observed.

Does fluctuating asymmetry of wing traits capture relative environmental stress in a lepidopteran?

Fluctuating asymmetry (FA) is hypothesized to be a useful predictor of population canalization, especially for organisms at risk from environmental change.Identification of traits that meet statistical criteria as FA measures remains a challenge.Here, a laboratory experiment subjected immature butterflies (Vanessa cardui) to diet and temperature conditions of varying stress levels. Variation in dietary macronutrient ratio (protein: carbohydrate) and rearing temperature (optimal: 25°C; elevated: 32°C) was introduced as stressors. Temperature and nutrition are key variables influencing ectotherm growth and fitness and so are likely to be important stressors that influence FA.Individuals subjected to stressful conditions were predicted to show elevated FA of three wing size traits, as well as increased mortality and decreased adult body size.Trait FA did not vary across treatments. Instead, treatment levels impacted viability: The combined incidence of pupal death and expression of significant wing malformations increased in treatment levels designated as stressful. Variation in adult dry mass also reflected predicted stress levels. Results suggest that individuals predicted to display increased FA either died or displayed gross developmental aberrations.This experiment illustrates important constraints on the investigation of FA, including selection of appropriate traits and identification of appropriate levels of stressors to avoid elevated mortality. The latter concern brings into question the utility of FA as an indicator of stress in vulnerable, natural populations, where stress levels cannot be controlled, and mortality and fitness effects are often not quantifiable.

Enduring neuroimmunological consequences of developmental experiences: From vulnerability to resilience.

The immune system is crucial for normal neuronal development and function (neuroimmune system). Both immune and neuronal systems undergo significant postnatal development and are sensitive to developmental programming by environmental experiences. Negative experiences from infection to psychological stress at a range of different time points (in utero to adolescence) can permanently alter the function of the neuroimmune system: given its prominent role in normal brain development and function this dysregulation may increase vulnerability to psychiatric illness. In contrast, positive experiences such as exercise and environmental enrichment are protective and can promote resilience, even restoring the detrimental effects of negative experiences on the neuroimmune system. This suggests the neuroimmune system is a viable therapeutic target for treatment and prevention of psychiatric illnesses, especially those related to stress. In this review we will summarise the main cells, molecules and functions of the immune system in general and with specific reference to central nervous system development and function. We will then discuss the effects of negative and positive environmental experiences, especially during development, in programming the long-term functioning of the neuroimmune system. Finally, we will review the sparse but growing literature on sex differences in neuroimmune development and response to environmental experiences.

Social Isolation Stress in Adolescence, but not Adulthood, Produces Hypersocial Behavior in Adult Male and Female C57BL/6J Mice.

Chronic stress during the developmental period of adolescence increases susceptibility to many neuropsychiatric diseases in adulthood, including anxiety, affective, and alcohol/substance use disorders. Preclinical rodent models of adolescent stress have produced varying results that are species, strain, sex, and laboratory-dependent. However, adolescent social isolation is a potent stressor in humans that has been reliably modeled in male rats, increasing adult anxiety-like and alcohol drinking behaviors, among others. In this study, we examined the generalizability and sex-dependence of this model in C57BL/6J mice, the most commonly used rodent strain in neuroscience research. We also performed a parallel study using social isolation in adulthood to understand the impact of adult social isolation on basal behavioral phenotypes. We found that 6 weeks of social isolation with minimal handling in adolescence through early adulthood [postnatal day (PD) 28-70] produced a hypersocial phenotype in both male and female mice and an anxiolytic phenotype in the elevated plus-maze in female mice. However, it had no effects in other assays for avoidance behavior or on fear conditioning, alcohol drinking, reward or aversion sensitivity, or novel object exploration in either sex. In contrast, 6 weeks of social isolation in adulthood beginning at PD77 produced an anxiogenic phenotype in the light/dark box but had no effects on any other assays. Altogether, our results suggest that: (1) adolescence is a critical period for social stress in C57BL/6J mice, producing aberrant social behavior in a sex-independent manner; and (2) chronic individual housing in adulthood does not alter basal behavioral phenotypes that may confound interpretation of behavior following other laboratory manipulations.

Heat stress during development affects immunocompetence in workers, queens and drones of Africanized honey bees (Apis mellifera L.) (Hymenoptera: Apidae).

Though social insects generally seem to have a reduced individual immunoresponse compared to solitary species, the impact of heat stress on that response has not been studied. In the honey bee, the effect of heat stress on reproductives (queens and males/drones) may also vary compared to workers, but this is currently unknown. Here, we quantified the activity of an enzyme linked to the immune response in insects and known to be affected by heat stress in solitary species: phenoloxidase (PO), in workers, queens and drones of Africanized honey bees (AHBs) experimentally subjected to elevated temperatures during the pupal stage. Additionally, we evaluated this marker in individuals experimentally infected with the entomopathogenic fungus Metarhizium anisopliae. Differences in PO activity were found between sexes and castes, with PO activity generally higher in workers and lower in reproductives. Such differences are associated with the likelihood of exposure to infection and the role of different individuals in the colony. Contrary to our expectation, heat stress did not cause an increase in PO activity equally in all classes of individual. Heat stress during the pupal stage significantly decreased the PO activity of AHB queens, but not that of workers or drones, which more frequently engage in extranidal activity. Experimental infection with Metarhizium anisopliae reduced PO activity in queens and workers, but increased it in drones. Notably, heat stressed workers lived significantly shorter after infection despite exhibiting greater PO activity than queens or drones. We suggest that this discrepancy may be related to trade-offs among immune response cascades in honey bees such as between heat shock proteins and defensin peptides used in microbial defence. Our results provide evidence for complex relationships among humoral immune responses in AHBs and suggest that heat stress could result in a reduced life expectancy of individuals.

Chronic stress, structural exposures and neurobiological mechanisms: A stimulation, discrepancy and deprivation model of psychosis.

Chronic stress exposure has been established as a key vulnerability factor for developing psychotic disorders, including schizophrenia. A structural, or systems level perspective, has often been lacking in conceptualizations of chronic stress for psychotic disorders. The current review thus identified three subtypes of structural exposures. Stimulation exposures included urban environments, population density and crime exposure, with intermediary mechanisms of lack of safety and high attentional demands. Underlying neural mechanisms included threat neural circuits. Discrepancy exposures included environmental ethnic density, income inequality, and social fragmentation, with intermediary mechanisms of lack of belonging and social exclusion, and neural mechanisms including the oxytocin system. Deprivation exposures included environments lacking socioeconomic, educational, or material resources, with intermediary mechanisms of lack of needed environmental enrichment, and underlying neural mechanisms of over-pruning and protracted PFC development. Delineating stressor etiology at the systems level is a necessary step in reducing barriers to effective interventions and health policy.