An analysis of risk factors for spontaneously occurring type 2 diabetes mellitus in rhesus macaques (Macaca mulatta).

BACKGROUND: Type 2 Diabetes Mellitus (T2D) is a chronic disease with a high prevalence worldwide. Human literature suggests factors beyond well-known risk factors (e.g., age, body mass index) for T2D: cytomegalovirus serostatus, season of birth, maternal age, birth weight, and depression. Nothing is known, however, about whether these variables are influential in primate models of T2D. METHODS: Using a retrospective methodology, we identified 22 cases of spontaneously occurring T2D among rhesus monkeys at our facility. A control sample of n = 1199 was identified. RESULTS: Animals born to mothers that were ≤5.5 years of age, and animals that showed heightened Activity and Emotionality in response to brief separation in infancy, had a greater risk for development of T2D in adulthood. CONCLUSIONS: Knowledge of additional risk factors for T2D could help colony managers better identify at-risk animals and enable diabetes researchers to select animals that might be more responsive to their manipulations.

Repeatability of measures of behavioral organization over two years in captive infant rhesus macaques, Macaca mulatta.

Individual differences of infant temperament have been associated with future health outcomes that provide explanatory power beyond adult personality. Despite the importance of such a metric, our developmental understanding of personality-like traits is poor. Therefore, we examined whether young primates show consistency in personality traits throughout development. We replicated a Biobehavioral Assessment (BBA) at three time periods: 3-4 months, 1 year, and 2 years of age in 47 rhesus macaque (Macaca mulatta) subjects from large mixed-sex outdoor social housing units at the California National Primate Research Center. We report results for tests focused on responses and adaptation to the temporary separation and relocation, responses to a threatening stimulus, and ratings of overall temperament. We found consistently repeatable associations in measures of Emotionality; these associations were stronger in males, but also present in females, and broadly consistent between Years 1 and 2. We also explored whether behavioral responses to this experimental relocation might be influenced by their experience being relocated for other reasons (i.e., hospitalizations) as individuals' responses might be influenced by similar experiences to the BBA procedure. Only locomotion, during one of the assessments, was associated with past hospitalization events. Overall, repeatability in Emotionality-associated behaviors was evident across the 2 years, in both sexes. We did, however, find evidence of the emergence of sex differences via differentiated expression of behavioral responses during the BBA. We emphasize that there is likely contextual nuance in the use of these BBA factor-associated behaviors. Further research is required to determine whether and how shifts occur in underlying factor structure and the expression of associated behaviors.

The Type I interferon antiviral gene program is impaired by lockdown and preserved by caregiving.

Previous research has linked perceived social isolation (loneliness) to reduced antiviral immunity, but the immunologic effects of the objective social isolation imposed by pandemic "shelter in place" (SIP) policies is unknown. We assessed the immunologic impact of SIP by relocating 21 adult male rhesus macaques from 2,000-m2 field cage communities of 70 to 132 other macaques to 2 wk of individual housing in indoor shelters. SIP was associated with 30% to 50% reductions in all circulating immune cell populations (lymphocytes, monocytes, and granulocytes), down-regulation of Type I interferon (IFN) antiviral gene expression, and a relative up-regulation of CD16- classical monocytes. These effects emerged within the first 48 h of SIP, persisted for at least 2 wk, and abated within 4 wk of return to social housing. A subsequent round of SIP in the presence of a novel juvenile macaque showed comparable reductions in circulating immune cell populations but reversal of Type I IFN reductions and classical monocyte increases observed during individual SIP. Analyses of lymph node tissues showed parallel up-regulation of Type I IFN genes and enhanced control of viral gene expression during juvenile-partnered SIP compared to isolated SIP. These results identify a significant adverse effect of SIP social isolation on antiviral immune regulation in both circulating immune cells and lymphoid tissues, and they suggest a potential behavioral strategy for ameliorating gene regulatory impacts (but not immune cell declines) by promoting prosocial engagement during SIP.

Paternal age in rhesus macaques is positively associated with germline mutation accumulation but not with measures of offspring sociability.

Mutation is the ultimate source of all genetic novelty and the cause of heritable genetic disorders. Mutational burden has been linked to complex disease, including neurodevelopmental disorders such as schizophrenia and autism. The rate of mutation is a fundamental genomic parameter and direct estimates of this parameter have been enabled by accurate comparisons of whole-genome sequences between parents and offspring. Studies in humans have revealed that the paternal age at conception explains most of the variation in mutation rate: Each additional year of paternal age in humans leads to approximately 1.5 additional inherited mutations. Here, we present an estimate of the de novo mutation rate in the rhesus macaque (Macaca mulatta) using whole-genome sequence data from 32 individuals in four large pedigrees. We estimated an average mutation rate of 0.58 × 10-8 per base pair per generation (at an average parental age of 7.5 yr), much lower than found in direct estimates from great apes. As in humans, older macaque fathers transmit more mutations to their offspring, increasing the per generation mutation rate by 4.27 × 10-10 per base pair per year. We found that the rate of mutation accumulation after puberty is similar between macaques and humans, but that a smaller number of mutations accumulate before puberty in macaques. We additionally investigated the role of paternal age on offspring sociability, a proxy for normal neurodevelopment, by studying 203 male macaques in large social groups.

Variation in infant rhesus monkeys' (Macaca mulatta) neutrophil-to-lymphocyte ratio is associated with environmental conditions, emotionality, and cortisol concentrations, and predicts disease-related outcomes.

The neutrophil-to-lymphocyte ratio (NLR) is a predictor of morbidity for a variety of medical conditions, but little is known about how variation in NLR arises. We examined variation in this measure in a sample of 4577 infant rhesus monkeys (54.8 % female), who participated in the BioBehavioral Assessment program at the California National Primate Research Center at 3-4 months of age. Lower values for NLR were seen for animals reared indoors, for animals that were raised to be free of specific pathogens, and for males. In addition lower NLR was associated with higher stress values of cortisol and with greater emotionality in response to an acute stressor. Finally, lower NLR in infancy was associated with greater risk for developing airways hyperresponsiveness (a hallmark of asthma); with display of diarrhea up to 3.97 years later; and with greater viral load when infected with the simian immunodeficiency virus at a mean of 6.1 years of age. Infant NLR was a better predictor of viral load than was a contemporaneously obtained measure of NLR. Infant and adult values of NLR were only modestly correlated; one reason may be that the infant measure was obtained during stressful conditions and the adult measure was obtained under baseline conditions. We propose that NLR is an integrated outcome measure reflecting organization and interaction of stress-response and immune systems. As such, assessment of NLR under conditions of stress may be a particularly useful marker of individual differences in morbidity, especially for conditions in which stress plays an important role, as in asthma, diarrhea/colitis, and AIDS.

Hair and plasma cortisol throughout the first 3 years of development in infant rhesus macaques, Macaca mulatta.

Cortisol expression has been demonstrated to have variation across development in rhesus macaques (Macaca mulatta). There exists contradictory evidence for the nature of this change, and age at which it occurs, across biological sample types. Consequently, we lack a cohesive understanding for cortisol concentrations across the development of a major human health translational model. We examined hair cortisol concentrations over the first 3 years of life for 49 mother-reared infant macaques from mixed-sex outdoor units at the California National Primate Research Center. For 48 of these subjects at infancy, 1 year, and 2 years, we obtained plasma cortisol samples for response to a stressor, adjustment to prolonged stress, and response to dexamethasone injection. Hair cortisol concentrations decreased dramatically between 3 and 10 months, followed by relative stability up to the final sampling event at around 34 months of age. Plasma cortisol showed within-year consistency, and consistency between infancy and year 1. We document variability in the infant plasma cortisol samples, especially in percent change between samples 1 and 2. Our plasma cortisol results indicate that infants possess the physiological capacity to effectively inhibit the release of cortisol when stimulated, as effectively as later responses in juveniles. Age-related changes in hair cortisol parallel findings indicating a large decline in the weeks following postparturation.

Infant inhibited temperament in primates predicts adult behavior, is heritable, and is associated with anxiety-relevant genetic variation.

An anxious or inhibited temperament (IT) early in life is a major risk factor for the later development of stress-related psychopathology. Starting in infancy, nonhuman primates, like humans, begin to reveal their temperament when exposed to novel situations. Here, in Study 1 we demonstrate this infant IT predicts adult behavior. Specifically, in over 600 monkeys, we found that individuals scored as inhibited during infancy were more likely to refuse treats offered by potentially-threatening human experimenters as adults. In Study 2, using a sample of over 4000 monkeys from a large multi-generational family pedigree, we demonstrate that infant IT is partially heritable. The data revealed infant IT to reflect a co-inherited substrate that manifests across multiple latent variables. Finally, in Study 3 we performed whole-genome sequencing in 106 monkeys to identify IT-associated single-nucleotide variations (SNVs). Results demonstrated a genome-wide significant SNV near CTNNA2, suggesting a molecular target worthy of additional investigation. Moreover, we observed lower p values in genes implicated in human association studies of neuroticism and depression. Together, these data demonstrate the utility of our model of infant inhibited temperament in the rhesus monkey to facilitate discovery of genes that are relevant to the long-term inherited risk to develop anxiety and depressive disorders.

Determination of dexamethasone dose for cortisol suppression in adult common marmosets (Callithrix jacchus).

We conducted a dose-response study of dexamethasone to investigate an optimal dexamethasone suppression test for common marmosets. Twelve marmosets received 0.1, 0.5, or 1.0 mg/kg dexamethasone. Doses of 0.5 and 1.0 mg/kg both suppressed endogenous cortisol for at least 18 h with greater individual variability in the lower 0.5 mg/kg dose.

The relationship of maternal rank, 5-HTTLPR genotype, and MAOA-LPR genotype to temperament in infant rhesus monkeys (Macaca mulatta).

Temperament is a construct whose manifestations are quantifiable from an early age, and whose origins have been proposed as "biological." Our goal was to determine whether maternal rank and infant genotype are associated with five measures of temperament in 3- to 4-month old rhesus monkeys (Macaca mulatta), all of whom were born and reared by their mothers in large, outdoor, half-acre cages. Maternal rank was defined as the proportion of animals outranked by each female, and the two genes of interest to us were monoamine oxidase and serotonin transporter, both of which are polymorphic in their promoter regions (MAOA-LPR and 5-HTTLPR, respectively), with one allele of each gene considered a "plasticity" allele, conferring increased sensitivity to environmental events. Our large sample size (n = 2014-3140) enabled us to examine the effects of individual genotypes rather than combining genotypes as is often done. Rank was positively associated with Confident temperament, but only for animals with the 5-repeat allele for MAOA-LPR. Rank had no other effect on temperament. In contrast, genotype had many different effects, with 5-HTTLPR associated with behavioral inhibition, and MAOA-LPR associated with ratings-based measures of temperament. We also examined the joint effect of the two genotypes and found some evidence for a dose-response: animals with the plasticity alleles for both genes were more likely to be behaviorally inhibited. Our results suggest phenotypic differences between animals possessing alleles for MAOA-LPR that show functional equivalence based on in vitro tests, and our data for 5-HTTLPR revealed differences between short/short homozygotes and long/short heterozygotes, strongly suggesting that combining genotypes for statistical analysis should be avoided if possible. Our analysis also provides evidence of sex differences in temperament, and, to our knowledge, the only evidence of differences in temperament based on specific pathogen-free status. We suggest several directions for future research.

Rhesus monkey sociality is stable across time and linked to variation in the initiation but not receipt of prosocial behavior.

Rhesus monkeys and humans are highly social primates, yet both species exhibit pronounced variation in social functioning, spanning a spectrum of sociality. Naturally occurring low sociality in rhesus monkeys may be a promising construct by which to model social impairments relevant to human autism spectrum disorder (ASD), particularly if low sociality is found to be stable across time and associated with diminished social motivation. Thus, to better characterize variation in sociality and social communication profiles, we performed quantitative social behavior assessments on N = 95 male rhesus macaques (Macaca mulatta) housed in large, outdoor groups. In Study 1, we determined the social classification of our subjects by rank-ordering their total frequency of nonsocial behavior. Monkeys with the greatest frequency of nonsocial behavior were classified as low-social (n = 20) and monkeys with the lowest frequency of nonsocial behavior were classified as high-social (n = 21). To assess group differences in social communication profiles, in Study 2, we quantified the rates of transient social communication signals, and whether these social signals were initiated by or directed towards the focal subject. Finally, in Study 3, we assessed the within-individual stability of sociality in a subset of monkeys (n = 11 low-social, n = 11 high-social) two years following our initial observations. Nonsocial behavior frequency significantly correlated across the two timepoints (Studies 1 and 3). Likewise, low-social versus high-social classification accurately predicted classification two years later. Low-social monkeys initiated less prosocial behavior than high-social monkeys, but groups did not differ in receipt of prosocial behavior, nor did they differ in threat behavior. These findings indicate that sociality is a stable, trait-like characteristic and that low sociality is linked to diminished initiation of prosocial behavior in rhesus macaques. This evidence also suggests that low sociality may be a useful construct for gaining mechanistic insight into the social motivational deficits often observed in people with ASD.

Structural differences in the hippocampus and amygdala of behaviorally inhibited macaque monkeys.

Behavioral inhibition is a temperamental disposition to react warily when confronted by unfamiliar people, objects, or events. Behaviorally inhibited children are at greater risk of developing anxiety disorders later in life. Previous studies reported that individuals with a history of childhood behavioral inhibition exhibit abnormal activity in the hippocampus and amygdala. However, few studies have investigated the structural differences that may underlie these functional abnormalities. In this exploratory study, we evaluated rhesus monkeys exhibiting a phenotype consistent with human behavioral inhibition. We performed quantitative neuroanatomical analyses that cannot be performed in humans including estimates of the volume and neuron number of distinct hippocampal regions and amygdala nuclei in behaviorally inhibited and control rhesus monkeys. Behaviorally inhibited monkeys had larger volumes of the rostral third of the hippocampal field CA3, smaller volumes of the rostral third of CA2, and smaller volumes of the accessory basal nucleus of the amygdala. Furthermore, behaviorally inhibited monkeys had fewer neurons in the rostral third of CA2. These structural differences may contribute to the functional abnormalities in the hippocampus and amygdala of behaviorally inhibited individuals. These structural findings in monkeys are consistent with a reduced modulation of amygdala activity via prefrontal cortex projections to the accessory basal nucleus. Given the putative roles of the amygdala in affective processing, CA3 in associative learning and CA2 in social memory, increased amygdala and CA3 activity, and diminished CA2 structure and function, may be associated with increased social anxiety and the heritability of behavioral inhibition. The findings from this exploratory study compel follow-up investigations with larger sample sizes and additional analyses to provide greater insight and more definitive answers regarding the neurobiological bases of behavioral inhibition.

The factor structure of the macaque social responsiveness scale-revised predicts social behavior and personality dimensions.

Most primate species are highly social. Yet, within species, pronounced individual differences in social functioning are evident. In humans, the Social Responsiveness Scale (SRS) measures variation in social functioning. The SRS provides a quantitative measure of social functioning in natural social settings and can be used as a screening tool for autistic traits. The SRS was previously adapted for use in chimpanzees and recently refined for rhesus macaques, resulting in the macaque Social Responsiveness Scale-Revised (mSRS-R). Here, we performed an exploratory factor analysis on the mSRS-R in a large sample of male rhesus macaques (N = 233). We investigated the relationships of the resulting mSRS-R factors to quantitative social behavior (alone, proximity, contact, groom, and play) and to previously-established personality dimensions (Sociability, Confidence, Irritability, and Equability). Factor analysis yielded three mSRS-R factors: Poor Social Motivation, Poor Social Attractiveness, and Inappropriate Behavior. mSRS-R factors mapped closely to social behavior and personality dimensions in rhesus macaques, providing support for this instrument's convergent and discriminant validity. Animals with higher Poor Social Motivation were more likely to be observed alone and less likely to be observed in contact and grooming with conspecifics. Animals with higher Poor Social Attractiveness were less likely to be observed playing but more likely to be observed grooming with conspecifics. Inappropriate Behavior did not predict any behavioral measure. Finally, animals with higher Poor Social Motivation and higher Poor Social Attractiveness had less sociable personalities, whereas animals with more Inappropriate Behavior were more confident and more irritable. These findings suggest that the mSRS-R is a promising, psychometrically robust tool that can be deployed to better understand the psychological factors contributing to individual differences in macaque social functioning and, with relevant species-specific modification, the SRS may hold promise for investigating variation in social functioning across diverse primate taxa.

Stress-induced plasma cortisol concentrations in infancy are associated with later parenting behaviors in female rhesus macaques (Macaca mulatta).

Few studies have longitudinally assessed the relationship between infant stress reactivity and future parenting style. Studies show that stress-induced plasma cortisol concentrations are stable over development and that they can be utilized as a marker for stress reactivity. This study investigates the relationship between stress-induced plasma cortisol concentrations in infancy and later parenting behavior in a translational nonhuman primate model. We hypothesized that higher stress-induced cortisol levels in infancy would predict impairments in maternal behaviors in adulthood. Subjects were rhesus macaque females (N = 122; Macaca mulatta), assessed as infants and again as mothers. At 3-4 months of age, subjects underwent a standardized BioBehavioral Assessment during which blood samples were obtained and they were assessed for behaviorally inhibition. Approximately 7 years later, subjects were observed as they interacted with their own offspring for four 300-s sessions. Typical rhesus monkey mother-offspring behaviors were recorded, including approaches and leaves and maternal cradling. Results showed that subjects' stress-induced cortisol concentrations and whether they exhibited behavioral inhibition as infants predicted later maternal behavior, with high cortisol concentrations and behavioral inhibition predicting high rates of offspring approaches and leaves and low rates of maternal cradling. Results also showed that higher stress-induced cortisol concentrations in infancy predicted higher scores on the Brown Index, an indication that the subjects' offspring, rather than the subject themselves, initiated changes in proximity. Taken together, these results suggest that individuals that exhibit higher stress-induced cortisol concentrations and behavioral inhibition at 3-4 months of age are at risk for engaging in less sensitive parenting behaviors as adults. To the extent that these findings generalize to humans, they suggest an important link between stress-induced cortisol concentrations and behavioral inhibition in infancy and behavior later in life, such that early-life stress reactivity can serve as a marker for later parenting behavior.

Ozone-induced enhancement of airway hyperreactivity in rhesus macaques: Effects of antioxidant treatment.

BACKGROUND: Ozone (O3) inhalation elicits airway inflammation and impairs treatment responsiveness in asthmatic patients. The underlying immune mechanisms have been difficult to study because of the lack of relevant experimental models. Rhesus macaques spontaneously have asthma and have a similar immune system to human subjects. OBJECTIVES: We sought to investigate mucosal immune changes after O3 inhalation in a clinically relevant nonhuman primate asthma model and to study the effects of an antioxidant synthetic lignan (synthetic secoisolariciresinol diglucoside [LGM2605]). METHODS: A cohort of macaques (n = 17) previously characterized with airway hyperreactivity (AHR) to methacholine was assessed (day 1). Macaques were treated (orally) with LGM2605 (25 mg/kg) or placebo twice per day for 7 days, exposed to 0.3 ppm O3 or air for 6 hours (on day 7), and studied 12 hours later (day 8). Lung function, blood and bronchoalveolar lavage (BAL) fluid immune cell profile, and bronchial brushing and blood cell mRNA expression were assessed. RESULTS: O3 induced significant BAL fluid neutrophilia and eosinophilia and increased AHR and expression of IL6 and IL25 mRNA in the airway epithelium together with increased BAL fluid group 2 innate lymphoid cell (ILC2s), CD1c+ myeloid dendritic cell, and CD4+ T-cell counts and diminished surfactant protein D expression. Although LGM2605 attenuated some of the immune and inflammatory changes, it completely abolished O3-induced AHR. CONCLUSION: ILC2s, CD1c+ myeloid dendritic cells, and CD4+ T cells are selectively involved in O3-induced asthma exacerbation. The inflammatory changes were partially prevented by antioxidant pretreatment with LGM2605, which had an unexpectedly disproportionate protective effect on AHR.

A new look at neurobehavioral development in rhesus monkey neonates (Macaca mulatta).

The Brazelton Neonatal Behavioral Assessment Scale (NBAS) evaluates a newborn infant's autonomic, motor, state, temperament, and social-attentional systems, which can help to identify infants at risk of developmental problems. Given the prevalence of rhesus monkeys being used as an animal model for human development, here we aimed to validate a standardized test battery modeled after the NBAS for use with nonhuman primates called the Infant Behavioral Assessment Scale (IBAS), employing exploratory structural equation modeling using a large sample of rhesus macaque neonates (n = 1,056). Furthermore, we examined the repeated assessments of the common factors within the same infants to describe any changes in performance over time, taking into account two independent variables (infant sex and rearing condition) that can potentially affect developmental outcomes. Results revealed three factors (Orientation, State Control, and Motor Activity) that all increased over the 1st month of life. While infant sex did not have an effect on any factor, nursery-rearing led to higher scores on Orientation but lower scores on State Control and Motor Activity. These results validate the IBAS as a reliable and valuable research tool for use with rhesus macaque infants and suggest that differences in rearing conditions can affect developmental trajectories and potentially pre-expose infants to heightened levels of cognitive and emotional deficiencies.

Behavioral effects of postnatal ketamine exposure in rhesus macaque infants are dependent on MAOA-LPR genotype.

Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist widely used in pediatric anesthetic and therapeutic practices and veterinary medicine. Previous evidence suggests that exposure to ketamine during sensitive periods of development results in neural apoptosis and atypical behavior. Since monoamine neurotransmitters play important roles in prenatal and early postnatal neural development, and since previous work suggests ketamine can inhibit monoamine transporters, we hypothesized that there would be behavioral consequences of prenatal and early postnatal exposure to ketamine moderated by genotype of the promoter in the monoamine oxidase-A (MAOA) gene. From a large sample of animals (N = 408), we compared groups of rhesus monkeys that had experienced a single exposure to ketamine during prenatal development, an exposure during prenatal development and one postnatal exposure, a postnatal exposure with no prenatal exposure, and no exposures. Animals were classified by putative activity levels for the MAOA genotype and were tested between 3 and 4 months of age on a battery of behavioral tests. Results suggested that animals exposed to ketamine postnatally, at a dose typically used for sedative effects that also had the low-activity variant of MAOA performed poorly on a visual memory test compared to animals with the high-activity variant of the MAOA gene.

Coping style and cortisol levels in infancy predict hair cortisol following new group formation in captive rhesus macaques (Macaca mulatta).

Social instability in primate groups has been used as a model to understand how social stress affects human populations. While it is well established that individual cercopithecines have different temperaments or personalities, little is known about how temperament mediates the experience of social instability in large, naturalistic groups. Here, we report findings from a study tracking a newly formed group of captive rhesus macaques (Macaca mulatta). We examine whether inter-individual differences in temperament during infancy affect physiological responses to new group formation years later, measured through hair cortisol 9 months after the group was formed. Our results show that early life measures of temperament characteristics predict later-life hypothalamic-pituitary-adrenal activity following new group formation, though not always in the directions we predicted. Individuals with higher blood cortisol concentrations in response to a novel stressor and lower blood cortisol concentrations following a Dexamethasone Suppression Test in infancy had lower hair cortisol values following new group formation later in life. Individuals characterized in infancy as more emotional or more active exhibited lower hair cortisol profiles 9 months after group formation. We suggest that these two temperament characteristics, emotionality and activity, may represent two different mechanisms leading to low hair cortisol values. That is, the physiological measure of low hair cortisol may have two different meanings depending on temperament characteristics of the individual. Our results demonstrate that temperament and physiological responsiveness measures in infancy can predict individual responses to a new group formation years later.

Personality, environmental stressors, and diarrhea in Rhesus macaques: An interactionist perspective.

Previous research has repeatedly shown both personality and psychological stress to predict gastrointestinal disorders and chronic diarrhea in humans. The goal of the present research was to evaluate the role of personality, as well as psychological stressors (i.e., housing relocations and rearing environment), in predicting chronic diarrhea in captive Rhesus macaques, with particular attention to how personality regulated the impact of such stressors. Subjects were 1,930 R. macaques at the California National Primate Research Center reared in a variety of environments. All subjects took part in an extensive personality evaluation at approximately 90-120 days of age. Data were analyzed using generalized linear models to determine how personality, rearing condition, housing relocations, and personality by environment interactions, predicted both diarrhea risk (an animal's risk for having diarrhea at least once) and chronic diarrhea (how many repeated bouts of diarrhea an animal had after their initial bout). Much like the human literature, we found that certain personality types (i.e., nervous, gentle, vigilant, and not confident) were more likely to have chronic diarrhea, and that certain stressful environments (i.e., repeated housing relocations) increased diarrhea risk. We further found multiple interactions between personality and environment, supporting the "interactionist" perspective on personality and health. We conclude that while certain stressful environments increase risk for chronic diarrhea, the relative impact of these stressors is highly dependent on an animal's personality.

Rhesus macaque personality, dominance, behavior, and health.

Previous studies of nonhuman primates have found relationships between health and individual differences in personality, behavior, and social status. However, despite knowing these factors are intercorrelated, many studies focus only on a single measure, for example, rank. Consequently, it is difficult to determine the degree to which these individual differences are independently associated with health. The present study sought to untangle the associations between health and these individual differences in rhesus macaques (Macaca mulatta). We studied 85 socially housed macaques at the Oregon and California National Primate Research Centers, and used veterinary records to determine the number of injuries and illnesses for each macaque. We measured personality using 12 items from a well-established primate personality questionnaire, performed focal observations of behaviors, and calculated dominance status from directional supplant data. All twelve personality questionnaire items were reliable and were used to represent five of the six personality dimensions identified in rhesus macaques-Dominance, Confidence, Openness, Anxiety, and Friendliness (also known as Sociability). Following this, we fit generalized linear mixed effects models to understand how these factors were associated with an animal's history of injury and history of illness. In the models, age was an offset, facility was a random effect, and the five personality dimensions, behavior, sex, and dominance status were fixed effects. Number of injuries and illnesses were each best represented by a negative binomial distribution. For the injury models, including the effects did improve model fit. This model revealed that more confident and more anxious macaques experienced fewer injuries. For the illness models, including the fixed effects did not significantly improve model fit over a model without the fixed effects. Future studies may seek to assess mechanisms underlying these associations.