Hormones and Behavior

Disruptions to maternal behaviors that emerge during the peripartum period have been shown to have lasting physiological and behavioral consequences for offspring. In addition to effects on offspring, disrupted maternal behaviors have been associated with peripartum mood and anxiety disorders. Therefore, it is critical for the wellbeing of both mother and offspring to identify upstream risk factors for the disruption of maternal behavior. We have previously found that pubertal stress leads to a blunted hypothalamic-pituitary-adrenal (HPA) axis response in peripartum humans and mice. Given that dysfunction of the HPA axis is associated with both PMADs and disrupted maternal behavior, we examined how pubertal stress influenced maternal behavior throughout peripartum in mice using a pup retrieval test. We found that pubertal stress led to faster pup retrieval, but a less predictable pattern of maternal behavior, as well as a blunted HPA axis response during pregnancy. We also examined whether maternal pubertal stress influenced offspring behavior in adolescence and adulthood. We found sex-specific differences in risk-taking behavior during adolescence that are no longer present in adulthood. Finally, we used in situ hybridization to examine gene expression during pregnancy in the medial preoptic area of the hypothalamus, a region implicated in maternal behavior. Following pubertal stress, we found cell-type specific changes in the expression of genes necessary for the expression of maternal behavior. Collectively, these findings contribute to our understanding of upstream risk factors for peripartum disruptions to maternal behavior and the lasting effects of pubertal stress on both mother and offspring.

Courtship is an essential component of reproductive success for many species and many courtship behaviors, such as vocalization, are energetically demanding. In order to successfully balance investment in courtship with feeding and foraging, individuals must be aware of their current energy balance, and hormonal signals of energetic state have been found to influence social signal effort across a variety of species. Ghrelin is one hormone that plays an important role in regulating energy balance by signaling hunger and promoting feeding. Previous studies have investigated the role of ghrelin in courtship, aggression, and mating behavior. In this study, we build on prior work by investigating the effects of ghrelin on ultrasonic vocalizations (USV) and other courtship behaviors of male mice. We expand on previous research by observing ghrelin's effects over longer interactions, allowing us to understand how ghrelin impacts the dynamics of USV production over time. Our results show that while males initially vocally court females at a high rate regardless of treatment, ghrelin reduces overall USV production by increasing the rate of decline of vocalization. Surprisingly, despite its effects on vocal courtship, we found no significant differences in the production or timing of other, non-vocal, courtship behaviors. This study deepens our understanding of the role of hormones traditionally associated with controlling hunger and feeding in regulating social behaviors.

Oxytocin (OT) and vasopressin (AVP) are neuropeptide hormones involved in regulating animal social behavior and a broad spectrum of physiological processes. Although their distributions are well documented in neuroendocrine regions of the forebrain and midbrain, their expression in the hindbrain remains poorly understood. Here, we used immunohistochemistry to quantify OT and AVP immunoreactive puncta within three auditory brainstem nuclei, the lateral superior olive (LSO), the medial superior olive (MSO), and the medial nucleus of the trapezoid body (MNTB) in six wild-caught rodent species differing in sociality. We also quantified the volume of these nuclei and examined variation in total brain volume across species and sociality. OT and AVP puncta count differed among species and social groups. Group-living species exhibited higher OT and AVP puncta counts than monogamous and solitary species in the LSO and MNTB. In the MSO, OT puncta counts did not differ among social groups, whereas AVP puncta counts were higher in group-living than in monogamous and solitary species. Total brain volume and the volumes of the MNTB and MSO differed among species, but not across social groups, whereas LSO volume did not differ among species or sociality. These findings revealed sociality-related variation in OT and AVP immunoreactive puncta within auditory brainstem circuits and suggest that neuropeptide signaling within early auditory brainstem pathways may contribute to the neural integration of social and auditory information.

Prenatal stress influences brain development; however, its long-term, region-specific effects on brain aging in males and females remain insufficiently characterized. This study examined the impact of unpredictable mild prenatal stress on behavior, cognition, and maternal care in C57BL/6J mice at middle (12 months) and old (18 months) ages. Stressed dams showed fragmented, unpredictable maternal behaviors, creating a stressful postnatal environment without impairing caregiving capacity. Both male and female offspring were born with lower birth weights and showed rapid postnatal growth, a trajectory associated with central insulin resistance and hippocampal signaling deficits. Sex-specific behavioral differences emerged with age. Middle-aged stressed males exhibited anhedonia, which progressed to hyperactivity, stereotypy, and persistent spatial memory deficits in old age. These outcomes corresponded with accelerated fronto-striatal decline, likely mediated by insulin resistance and increased rigidity of medial prefrontal cortex structures due to diminished local estrogenic activity. In contrast, middle-aged stressed females displayed hypoactivity and reduced anxiety, later developing anhedonia in old age while maintaining hippocampus-dependent memory. In females, this pattern supports a model in which a neuroestrogen - and growth factor-dependent feedback loop transiently preserves hippocampal plasticity but compromises dopaminergic function in reward circuits. This balance may deteriorate with reproductive senescence. Both sexes retained cognitive flexibility, indicating domain-specific rather than global cognitive impairment. These findings demonstrate that excessive prenatal glucocorticoid exposure and unpredictable postnatal care produce a combined hormonal and metabolic insult, resulting in sexually divergent trajectories of brain aging. The results underscore the necessity of incorporating sex as a biological variable in fetal programming research across the lifespan.

Male-biased cooperative behaviours that produce public goods (male services) are widespread in primates. Recent behavioural studies suggest that male services may function beyond paternal investment, either as displays of competitive ability or as honest signals eliciting female choice. Because these hypotheses make contrasting predictions about the physiological state of service providers, endocrine measures offer a complementary approach for distinguishing between them. We investigated whether long-term testosterone and cortisol concentrations, measured from hair samples, were associated with four male services in wild vervet monkeys: alarm calling, participation in between-group conflicts (BGCs), leading river crossings, and sentinelling. Testosterone and cortisol concentrations increased with male competitive status, measured as a combination of dominance rank and recent rank trajectory, particularly during the mating period, establishing the endocrine profile associated with competition. In contrast, most male services showed few relationships with hormone concentrations: participation in BGCs was associated with lower cortisol concentrations and, to a lesser extent, lower testosterone concentrations. Because BGC participation is the strongest predictor of male mating frequency in this population, these findings indicate that males contributing to BGCs present an endocrine profile distinct from that associated with competitive state and instead support the prediction that high-quality males, irrespective of their dominance rank, can perform costly cooperative behaviours while maintaining relatively low physiological costs. More broadly, our results provide physiological support for reputation-based partner choice as a mechanism contributing to the maintenance of male services in primates.

Stressors experienced during the postnatal period may increase vulnerability to mental health disorders, including postpartum depression and anxiety. In rodents, maternal separation (MS) has been shown to alter behaviours in dams, but these observations have been made almost exclusively in rats and thus robust mouse models of postpartum mental health disorders using this stressor remain limited. Here we first examined, in mice, the effects of MS on maternal caregiving and on anxiety- and depressive-like behaviours. As stress-induced inflammatory activation in the gut-brain axis has been associated with behavioural alterations in non-postpartum contexts, changes in pro-inflammatory cytokines and tight junction proteins in the brain and intestinal tract were also examined. Female C57BL/6N mice were assigned to a No Separation (NS) or a MS condition that consisted of 3-hour daily separation sessions from postnatal days (P) 2 to 14. Maternal care behaviours were assessed on P3 and P7, followed by anxiety- and depressive-like behaviours on P22 and P23, and the collection of the medial prefrontal cortex (mPFC) and colon on P24 to determine the expression of selected genes. Caregiving patterns in MS dams fluctuated throughout the early postnatal period. Although behaviours and gene expression outcomes remained unchanged by MS, grooming time in the splash test was correlated with the expression of different genes in the mPFC. These findings suggest that C57BL/6 mouse dams may be less sensitive to the actions of MS on behaviour and on brain and intestinal markers of inflammation and barrier permeability, at least when examined shortly after weaning.

Stressful experiences are a major risk factor for the development of neuropsychiatric disorders in vulnerable individuals. Identifying features that can distinguish stress-susceptible from resilient individuals remains a central goal in stress neurobiology. Due to the routine exclusion of female subjects from stress research or the use of male-defined criteria in behavioral characterization of subjects post-stress, female stress responses and vulnerability profiles remain poorly understood. This work aimed to gain a better understanding of sex-specific stress responses to social defeat stress. Here, we used a novel paired male-female social defeat paradigm and tracked subjects longitudinally in a ''two-hit'' design to evaluate responses to both acute social defeat stress (ASDS) and chronic social defeat stress (CSDS), and to determine how prior stress exposure influences subsequent vulnerability. We found that both ASDS and CSDS induces changes in social avoidance/approach behavior in males but not females, as measured by a classic social interaction ratio. Prior ASDS exposure enhanced susceptibility to subsequent CSDS most clearly in males, with females displaying specific changes in corner zone occupancy. Furthermore, we observed divergent anxiety profiles between males and females in a post-stress behavioral battery. Finally, females exhibited specific stress-related locomotor responses following ASDS. Together, these findings suggest that females may adopt distinct behavioral strategies following social defeat stress.

Social animals must identify, evaluate, and appropriately respond to other individuals, often relying on multiple sources of information to guide context-dependent behavior. While individual recognition is thought to be widespread and critical for many social interactions (e.g. territoriality, dominance hierarchies), convincing demonstrations across animals beyond class-level recognition remain rare. Further, the cues animals use to recognize individuals remains poorly understood, especially in natural environments where they are exposed to numerous cues which may require cue integration. Here, we examine how socially dominant males of the African cichlid fish, Astatotilapia burtoni, use individual recognition to modulate aggression and whether this process depends on the spatial context. Using naturalistic experimental setups, we exposed males to familiar and unfamiliar neighbors while systematically manipulating spatial location and presenting a neighbor either singly or simultaneously to simulate competing social cues. Additionally, we measured circulating testosterone to assess endocrine correlates of recognition and aggression. We found that focal males habituated to familiar neighbors only when they remained in a consistent territorial location, demonstrating that spatial context is important for recognition. Further, when familiar and unfamiliar neighbors were presented simultaneously, males preferentially aggressed toward unfamiliar rival and adjust their aggressive response to the perceived threat of their neighbors, indicating that identity-based threat assessment is maintained under competing social demands. Together, our results show that recognition is a flexible, multi-faceted process that depends on the integration of identity and contextual information to guide territorial decision-making under dynamic social conditions.

Objective: Women with premenstrual syndrome (PMS) experience affective lability, irritability, depressed mood, and anxiety during the late luteal phase of the menstrual cycle. Stress reactivity may contribute to the development of these symptoms, yet neural correlates remain unexplored. We examined neural, behavioral and endocrine stress responses across menstrual cycle phases in women with and without PMS. Methods: 26 women with PMS and 24 women without PMS participated in two fMRI sessions, during the mid-follicular (days 5 to 11) and late-luteal phases (days -7 to -1). Participants completed the Montreal Imaging Stress Task (MIST). Subjective stress ratings and salivary cortisol were collected at six time points before and after stress induction. Stress-related brain activation was assessed using whole-brain and region-of-interest analyses. Results: Subjective stress ratings increased as expected from before to after the MIST, with no group or phase differences. Salivary cortisol was significantly higher during the mid-follicular phase, with no group effect or significant pre-post MIST difference. While the stress task elicited activation patterns in stress-related regions, whole-brain analysis revealed no significant effects of group (PMS vs. no PMS) or menstrual cycle phase (follicular vs. luteal) on the neural stress response. Considering premenstrual symptom severity as a predictor revealed significant group-by-symptom severity interactions in the right inferior frontal gyrus and the right superior temporal gyrus. Conclusion: Using a within-subject repeated-measures design, we found neural responses to psychosocial stress to be stable across menstrual cycle phases. Individual differences in symptom severity may nevertheless be associated with differences in stress-related brain activation.

Menopause is a major neuroendocrine transition characterised by substantial changes in endocrine milieu, physiological, psychological, and psychosexual health. Although menopausal symptoms are common, their range and severity vary considerably between individuals, suggesting that menopause is a multifaceted process. Endocrine markers (luteinising, follicle-stimulating & anti-Mullerian hormone), together with perceived well-being, may contribute to this variability. Thus, the aim was to capture the complex impact of endocrine and well-being markers on psychosexual health and menopausal symptoms. Therefore, we first applied principal component analyses to identify individual endocrine and well-being profiles, to then assess their association with psychosexual health and menopausal symptoms in pre- and post-menopausal females. Post- compared to pre-menopausal females report reduced psychosexual health and greater urogenital and psychological menopausal symptom burden. Endocrine and well-being profiles interact with reproductive status: Post-menopausal females with lower subjective well-being and a stronger menopause-like endocrine milieu report decreased overall psychosexual health and more sexual related pain. Additionally, endocrine milieu interacted with reproductive status on urogenital symptoms: Post-menopausal females with a stronger menopause-like endocrine milieu report less urogenital symptoms. Together, these findings suggest that endocrine factors and subjective well-being jointly influence psychosexual health and menopausal symptoms after menopause. No association is seen before menopause. Therefore, females after menopause need to be considered separately in research and clinic. Multivariate analyses capture patterns that are not identified using individual biomarkers and conventional univariate approaches. Our findings highlight the value of integrative multivariate approaches for improving the assessment of menopausal health and characterising individual variability across the menopausal transition.

Sex-steroid hormones influence brain structure across aging, but their relationship to the cerebellum, a region implicated in cognition and vulnerable to age-related decline, remains poorly characterized, particularly longitudinally and across both sexes. We examined whether 17{beta}-estradiol, progesterone, and testosterone relate to cerebellar volume across two timepoints, and whether these relationships differ by sex. In a mixed-sex sample of aging adults (Baseline N = 137; Year 1 N = 93), free salivary hormones and cerebellar lobular volumes were quantified. Linear regression tested cross-sectional, predictive, and change-score hormone-volume associations, and formal hormone-by-sex interactions, in a priori primary and secondary cerebellar lobules of interest. Hormone-cerebellum relationships were consistently sex-differentiated. Estradiol change related to Crus I volume change in opposite directions in males and females, a dissociation extending across bilateral Crus I and Lobule VI, and Right Crus II. In females, greater increases in testosterone were associated with greater decline in Left Crus I and Right Lobule V volumes. In males, testosterone showed no significant associations in primary analyses, however, increases in estradiol were associated with larger volumes. Progesterone showed a male-specific cross-sectional association with Crus II. Several relationships ran opposite to the direction predicted by estradiols established neurotrophic role. Sex-steroid influences on the aging cerebellum are sex-differentiated, regionally specific, and may not be predicted exclusively by cortical or female-focused models. These findings establish the cerebellum as a potential site of sex-specific hormonal influence on brain aging and also further highlight the complexity of the impact of sex-steroid hormones on the aging brain.

Extensive work has established that exposure to a single acute stressor can have profound impacts on future reactivity to new stressors, including enhanced acquisition of new fear. The impact of stressor type on development of stress sensitization, however, remains unclear. We investigated whether fundamentally different acute stressors (shock, social defeat, or restraint stress) differ in ability to sensitize acquisition of a new, contextually distinct fear memory in adult male mice two weeks following stress exposure. Stressor subtype differentially sensitized new fear learning; specifically, shock and social defeat - but not restraint stress - led to enhanced recall of a new shock-paired fear memory. We also compared how stressor subtypes differentially engage the brain-periphery interactions that regulate stress responsivity. Notably, restraint stress, which did not lead to fear sensitization to foot shock, drove similar or even greater corticosterone release than other stressors, suggesting that the neuroendocrine response to the original stressor is dissociable from development of a behavioural fear sensitization response. Using the immediate-early gene FOS as a marker of neural activity, all conditions - including the context-only control condition - activated a similar number of neurons in the basolateral amygdala. In contrast, only stressful conditions activated the paraventricular nucleus of the hypothalamus, and restraint stress selectively spared activation of the dorsal hippocampus. These data collectively suggest that future responses to stress depend critically on the identity of previously experienced stressors, rather than simply on prior exposure to stress, establishing a powerful comparative model for investigating the specific mechanisms underlying stress-enhanced fear learning.

It is estimated that approximately fifty percent of the population will encounter at least one traumatic event during their lifetime; however, only six percent develop Posttraumatic Stress Disorder (PTSD), a trauma-related disorder characterized by persistent alterations in affect and cognition, including an exaggerated fear response. It is well established that females (9.7%) are more than twice as likely as males (3.6%) to be diagnosed with PTSD. Nevertheless, a significant challenge remains in understanding how the severity of traumas experienced in childhood versus adulthood influences PTSD development across sexes. To address this challenge effectively, the adoption of preclinical animal models that accurately reflect these key characteristics is crucial. The Stress Enhanced Fear Learning (SEFL) paradigm in rodents encapsulates some of these complexities associated with PTSD, such as persistent fear sensitization following exposure to acute trauma. This study investigates how stress severity and developmental timing affect the long-term maintenance of SEFL in male and female rats. Juvenile and adult rats were initially subjected to no stress (control, context only), low stress (1 footshock), moderate stress (3 footshocks), or high stress (15 footshocks), followed by an extinction session either one day (recent) or sixty days (remote) later. Subsequently, to evaluate SEFL in a new context, all subjects received a single footshock and were tested the following day. Shortly after stress induction, all groups displayed SEFL. Although the effects persisted for sixty days in adult males and juvenile females, even at the lowest stress level, they were significantly reduced in juvenile males and adult females. These findings offer novel insights into sex-related differences in the persistence of SEFL and introduce new considerations regarding how the timing of developmental stressors influences future threat encoding and fear responses.

Abstract The importance of hypothalamic kisspeptin (Kiss1) neurons in controlling the reproductive axis is well established, while a population of extra-hypothalamic Kiss1 neurons is found in the medial amygdala (MeA) of both males and females in rodents and is less well understood. The MeA is connected with the olfactory bulbs, the hypothalamus and cortical areas. MeA Kiss1 neurons have been implicated in sexual behaviour and modulation of the reproductive axis; however, little is known about their action potential firing properties, which would influence kisspeptin release in target brain regions, nor whether their physiological properties are sex- or estrous cycle-dependent. In this study, whole-cell patch-clamp recordings were made from Kiss1 neurons in brain slices containing the MeA of adult female (estrous and diestrous) and male mice. MeA Kiss1 (Kiss1MeA) neurons were sexually dimorphic, with greater numbers in male compared to female mice and a slower change in excitability in estrous females compared with males. However, combining a range of electrophysiological parameters using principal component analysis did not reveal a distinct sex- or estrous cycle-linked phenotype, suggesting that the properties of Kiss1MeA neurons- and therefore kisspeptin release- are broadly similar. Interestingly, Kiss1MeA neurons had unique electrophysiological properties compared with anteroventral periventricular (AVPV) hypothalamic Kiss1 (Kiss1AVPV) neurons in female mice; with their reduced excitability, achieving action potential firing frequencies greater than 10Hz required a larger current input, indicating that Kiss1MeA neurons require stronger synaptic input to achieve firing frequencies that drive kisspeptin release. These findings provide new information about the physiological properties of Kiss1MeA neurons, showing subtle sex differences and profound regional differences between the MeA and AVPV.

The success of modern antiretroviral therapy (ART) has increased the life expectancy of people living with HIV to levels approaching that of uninfected individuals. For women living with HIV (WLWH), this means that more will survive to undergo menopause and experience the consequences of decreased ovarian hormone levels, particularly estrogen (E2). The recent change in federal guidance for use of postmenopausal hormone therapy is increasing demand for both E2-alone and E2+progestogen formulations to control adverse symptoms of menopause. The consequences and efficacy of hormone therapy in WLWH are thus an important issue for WLWH and their healthcare providers. The role of E2 replacement in postmenopausal WLWH is a significant issue because of its potential effects on control the viral reservoir and its demonstrated beneficial metabolic effects in uninfected postmenopausal women. To address these questions, we employed a novel nonhuman primate model of postmenopausal WLWH undergoing E2 replacement. Reproductively competent female rhesus macaques were infected with simian immunodeficiency virus (SIV) and then subjected to a daily ART regimen. After complete suppression of plasma viremia, all animals were ovariectomized (OVX) and then implanted with Silastic capsules containing either cholesterol vehicle or sufficient E2 to restore pre-OVX plasma levels. Plasma and cell-associated viral dynamics, immune responses, body composition, systemic and tissue-specific metabolic parameters, cytokine profiles, and parameters of bone health were followed longitudinally from baseline through 34 weeks of E2 deficiency or replacement. We found that E2 status did not significantly affect plasma or tissue viral dynamics or overall metabolic homeostasis. However, E2 replacement exerted beneficial effects on several aspects of bone health in spite of a chronic inflammatory state that persisted following effective ART suppression of the SIV reservoir. Our findings suggest that hormone therapy, specifically E2 replacement, offers benefit to WLWH, particularly with respect to bone loss.

Female-female competition is increasingly recognized as a key driver of female ornamentation, including birdsong, which often functions in intrasexual competition. However, the specific resources females use elaborate traits to compete for remain unclear. In addition, few studies have simultaneously investigated the use of multiple competitive traits in females, despite growing independent interest in these traits (e.g., female song and aggression). We investigated the competitive contexts of female song, aggression and calling behavior in northern house wrens (Troglodytes aedon) to determine which resources females compete for across the breeding season. We simulated conspecific territorial intrusions using female song at three breeding stages representing different contexts: arrival (mate and territory acquisition), nest building (nest site and breeding status defense), and egg laying (brood defense). We tested whether female song and physical aggression varied as reproductive resources shifted across the breeding cycle. Females were significantly more aggressive during nest building, showing 5.8 times greater odds of a higher-intensity aggressive response during nest building compared to arrival. Female song output was similar across early stages but declined during egg laying, though this was not statistically significant after correction for multiple comparisons and individuals varied substantially in overall singing propensity. Non-song vocalizations varied by call type and breeding stage. Calls associated with aggression occurred most frequently during nest building, consistent with peak physical aggression responses. Together, these results identify nest building as the stage of highest female aggression, consistent with heightened competition over nest cavities and associated breeding status in this cavity-nesting species. In contrast, female song occurred across all stages and appears to function in multiple competitive contexts. This study provides evidence for context and mode-specific female signaling in a temperate songbird and highlights that females strategically use aggression, calls, and song to mediate social conflict across breeding contexts.

The phenotype of a focal individual can be affected not only by the individuals own genes (direct genetic effects, DGE) but also by genes of other individuals it interacts with (indirect genetic effects, IGE). Better understanding IGE can help better understand the impact and mechanisms of social effects. Here, we investigated, in laboratory mice, the modulation of IGE by genetic background of the focal individual (social epistasis) and by sex. We focused on IGE arising from Epha4, a gene that has been associated with the individuals own stress-related and social behaviours (i.e. DGE) and the stress-coping behaviour and wound healing of the other mice in the cage (i.e. IGE). Among four different genetic backgrounds for focal mice, significant IGE from Epha4 were detected in CBA females only. A formal model selection analysis was consistent with the modulation of IGE by the similarity of the genetic backgrounds of the focal mouse and its Epha4 cage mate, as well as by sex. Observations of fighting in cages of males with dissimilar genetic backgrounds suggested aggression might underpin these modulatory effects, which prompted to us to expand the conceptual framework describing the mechanisms of social epistasis. Thus, our results strengthen the emerging view that IGE are not fixed properties of social genotypes but can depend on the genetic and sex context of interacting individuals, revealing an underexplored layer of their genetic architecture.

Adverse childhood experiences like social isolation (SI) contribute to long term negative health outcomes and the development of severe psychiatric disorder. Adolescence is a unique period of coordinated social and motivational system development driven by dopamine (DA) signaling. Microglia, immune cells of the brain, may play a unique role in regulating SI-induced DA system changes and associated behavioral dysfunction. Male microglia refine dopamine D1 receptors (D1rs) in the nucleus accumbens (NAc) of adolescent male rats shaping play behavior. Here we characterized the molecular developmental impacts of postweaning SI from P21-P38, with a resocialization period to P54. We tested the role of microglial engulfment of D1rs in mediating behavioral consequences of SI using neutrophil inhibitory factor (NIF) to block complement-mediated engulfment required for D1r pruning. We found sex specific impacts of SI on brain development and the DA system. In SI males, microglia engulf more NAc D1rs than group housed (GH) controls. Within GH animals, NAc D1r density is positively correlated to play and allogrooming. In SI animals, NAc D1r density is negatively correlated to biting behavior, and is not correlated to play or allogrooming. Pharmacologically inhibiting microglial engulfment of D1r via bilateral NAc NIF injection prevents observed D1r:behavior correlations in GH and SI animals. NIF treatment interacts with SI, exaggerating aggressive-like behavior, showing a role for microglia in regulating aggressive-like behavior via complement pruning in adolescence. Microglia may play a unique role in regulating behavior that drive negative health outcomes in the face of developmental stress, including SI.

Social relationships can buffer individuals against environmental challenges, reducing the physiological costs of disturbance. Assessing how social and environmental conditions jointly shape physiological stress is critical for predicting individual responses to disturbance, particularly in managed populations. We evaluated whether social and environmental stressors act additively or whether social context modifies physiological responses to environmental challenges. We combined behavioural data and faecal glucocorticoid metabolite samples from a small, intensively monitored population of African elephants (Loxodonta africana) in a fenced reserve. Using a Bayesian framework, we tested how social factors interacted with variation in the biophysical environment, including natural environmental and anthropogenic disturbances, to predict glucocorticoid concentrations. Natural environmental variables, including weather, water availability, and season, did not predict glucocorticoid concentrations. In contrast, helicopter use, a common management intervention, was associated with higher glucocorticoid concentrations. Social effects were context dependent. Following disturbance, low-ranking individuals showed higher glucocorticoid concentrations than high-ranking individuals, whereas this pattern reversed under low-disturbance conditions. Individuals with more social connections had lower glucocorticoid concentrations, but this effect was evident only under non-disturbance conditions. Measures of betweenness centrality did not predict glucocorticoid levels. These results demonstrate that social factors mediate physiological responses to anthropogenic disturbance and that management actions can impose uneven physiological costs across individuals. Quantifying interactions between social factors and the biophysical environment may improve conservation and management strategies for social species. Integrating physiological responses to interactions between social factors and the biophysical environment can guide conservation strategies and improve management interventions in social species.

Early-life adversity is associated with highly variable developmental outcomes, but identifying sources of this heterogeneity is difficult because variation in outcome is typically accompanied by variation in exposure. Animal models provide experimental leverage by standardizing features of the early environment while allowing variation in developmental experience and outcome to remain observable. Using a graded limited bedding and nesting model spanning normative rearing, moderate restriction, and severe scarcity, we asked what distinguishes social outcomes among animals exposed to the same resource restriction. Severe scarcity increased adverse maternal handling while leaving organized nurturing behaviors intact. Following the P8-P12 rearing manipulation, pups were tested outside the home cage in a P13 social approach assay. Severe scarcity reduced the proportion of pups that approached the dam, but outcomes varied substantially among scarcity litters. Greater typical maternal pup transport predicted greater approach, whereas a greater proportion of rough transport predicted poorer approach. Transport composition did not differ across rearing conditions, but its relationship with social behavior did. Amygdala intercalated-cell recruitment also covaried with social approach under severe scarcity despite limited condition-level differences in regional c-Fos. Plasma corticosterone differed across rearing conditions but did not covary detectably with the principal caregiving, behavioral, or neural measures. Maternal transport and intercalated-cell recruitment were not robustly associated, identifying separable experiential and neural correlates of behavioral variation. These findings show that standardizing an environmental constraint does not produce uniform developmental experience or outcome, and that caregiving experiences preserved across rearing conditions can distinguish social outcomes under severe scarcity.