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1.  The Development of the Hypothalamic–Pituitary–Adrenal Axis in Rhesus Monkeys: Effects of Age, Sex, and Early Experience 
Developmental psychobiology  2012;56(1):86-95.
We investigated the development of the HPA axis in group-living rhesus monkeys. Forty-three infants were studied from birth through their third year of life; 22 infants were physically abused by their mothers, while 21 infants were not abused. Plasma cortisol levels in basal conditions and in response to a novel environment test were assessed at 6-month intervals. Both basal and stress cortisol increased steadily from 6 to 24 months of age and then dropped. Across all ages, stress cortisol levels were significantly higher than the basal levels. The cortisol responses to stress at 30 and 36 months of age were significantly lower than the responses at all other ages. At most ages there was an inverse relationship between basal and stress cortisol levels. Individual differences in basal cortisol levels were generally stable in the first 2 years and more variable in the third year while the opposite for true for cortisol responses to stress. At the end of the first year, but not later in life, abused infants had higher cortisol levels than controls across the basal and stress conditions. Rates of social interactions with the mother and other group members were positively correlated with basal cortisol levels early in life, and with cortisol responses to stress later in life. Altogether, these results indicate that there are strong individual differences in HPA function, that there is a relationship between basal activity and stress reactivity, and that early abuse has the short-term effect of increasing both basal activity and stress reactivity.
doi:10.1002/dev.21093
PMCID: PMC4005596  PMID: 23192465
stress; HPA axis; development; early experience; individual differences; rhesus monkeys
2.  Is male rhesus macaque red color ornamentation attractive to females? 
Behavioral ecology and sociobiology  2014;68(7):1215-1224.
Male sexually-selected traits can evolve through different mechanisms: conspicuous and colorful ornaments usually evolve through inter-sexual selection, while weapons usually evolve through intra-sexual selection. Male ornaments are rare among mammals in comparison to birds, leading to the notion that female mate choice generally plays little role in trait evolution in this taxon. Supporting this view, when ornaments are present in mammals they typically indicate social status and are products of male-male competition. This general mammalian pattern, however, may not apply to rhesus macaques (Macaca mulatta). Males of this species display conspicuous skin coloration, but this expression is not correlated to dominance rank, and is therefore unlikely to have evolved due to male-male competition. Here, we investigate whether male color expression influences female proceptivity towards males in the Cayo Santiago free-ranging rhesus macaque population. We collected face images of 24 adult males varying in dominance rank and age at the peak of the mating season, and modeled these to rhesus macaque visual perception. We also recorded female socio-sexual behaviors towards these males. Results show that dark red males received more sexual solicitations, by more females, than pale pink ones. Together with previous results, our study suggests that male color ornaments are more likely to be a product of inter- rather than intra-sexual selection. This may especially be the case in rhesus macaques due to the particular characteristics of male-male competition in this species.
doi:10.1007/s00265-014-1732-9
PMCID: PMC4167843  PMID: 25246728
Ornaments; sexual selection; female mate choice; sexual skin; color; anthropoid primates
3.  Effect of mating activity and dominance rank on male masturbation among free-ranging male rhesus macaques 
Ethology : formerly Zeitschrift fur Tierpsychologie  2013;119(11):10.1111/eth.12146.
The adaptive function of male masturbation is still poorly understood, despite its high prevalence in humans and other animals. In non-human primates, male masturbation is most frequent among anthropoid monkeys and apes living in multimale-multifemale groups with a promiscuous mating system. In these species, male masturbation may be a non-functional by-product of high sexual arousal or be adaptive by providing advantages in terms of sperm competition or by decreasing the risk of sexually transmitted infections. We investigated the possible functional significance of male masturbation using behavioral data collected on 21 free-ranging male rhesus macaques (Macaca mulatta) at the peak of the mating season. We found some evidence that masturbation is linked to low mating opportunities: regardless of rank, males were most likely to be observed masturbating on days in which they were not observed mating, and lower-ranking males mated less and tended to masturbate more frequently than higher-ranking males. These results echo the findings obtained for two other species of macaques, but contrast those obtained in red colobus monkeys (Procolobus badius) and Cape ground squirrels (Xerus inauris). Interestingly, however, male masturbation events ended with ejaculation in only 15% of the observed masturbation time, suggesting that new hypotheses are needed to explain masturbation in this species. More studies are needed to establish whether male masturbation is adaptive and whether it serves similar or different functions in different sexually promiscuous species.
doi:10.1111/eth.12146
PMCID: PMC3810986  PMID: 24187414
Masturbation; auto-erotism; male-male competition; sexually-transmitted disease; sexual arousal; mating success; dominance rank; rhesus macaques
4.  Signaling in multiple modalities in male rhesus macaques: sex skin coloration and barks in relation to androgen levels, social status, and mating behavior 
Behavioral ecology and sociobiology  2013;67(9):1457-1469.
The past decade has seen an increasing shift in animal communication towards more studies that incorporate aspects of signaling in multiple modalities. Although nonhuman primates are an excellent group for studying the extent to which different aspects of condition may be signaled in different modalities, and how such information may be integrated during mate choice, very few studies of primate species have incorporated such analyses. Here, we present data from free-ranging male rhesus macaques on sex skin coloration (modeled to receiver perception), bark vocal signals, androgen levels, morphometric variables, dominance status, and female mate choice. We show that, consistent with data on females, most intra- and interindividual variation in sex skin appearance occurs in luminance rather than color. Sex skin luminance was significantly correlated across different skin regions. Sex skin luminance did not correlate with the majority of bark parameters, suggesting the potential for the two signals to convey different information. Sex skin appearance was not related to androgen levels although we found some evidence for links between androgen levels and bark parameters, several of which were also related to morphometric variables. We found no evidence that either signal was related to male dominance rank or used in female mate choice, though more direct measures of female proceptive behavior are needed. Overall, the function of male sex skin coloration in this species remains unclear. Our study is among the first nonhuman primate studies to incorporate measurements of multiple signals in multiple modalities, and we encourage other authors to incorporate such analyses into their work.
doi:10.1007/s00265-013-1521-x
PMCID: PMC4084859  PMID: 25013266
Coloration; Luminance; Vocal signals; Multimodal; Primate; Rhesus macaques
5.  When Violence Pays: A Cost-Benefit Analysis of Aggressive Behavior in Animals and Humans 
An optimization analysis of human behavior from a comparative perspective can improve our understanding of the adaptiveness of human nature. Intra-specific competition for resources provides the main selective pressure for the evolution of violent aggression toward conspecifics, and variation in the fitness benefits and costs of aggression can account for inter-specific and inter-individual differences in aggressiveness. When aggression reflects competition for resources, its benefits vary in relation to the characteristics of the resources (their intrinsic value, abundance, spatial distribution, and controllability) while its costs vary in relation to the characteristics of organisms and how they fight (which, in turn, affects the extent to which aggression entails risk of physical injury or death, energetic depletion, exposure to predation, psychological and physiological stress, or damage to social relationships). Humans are a highly aggressive species in comparison to other animals, probably as a result of an unusually high benefit-to-cost ratio for intra-specific aggression. This conclusion is supported by frequent and widespread occurrence of male-male coalitionary killing and by male-female sexual coercion. Sex differences in violent aggression in humans and other species probably evolved by sexual selection and reflect different optimal competitive strategies for males and females.
PMCID: PMC3859192  PMID: 23864299
aggression; evolution; optimization; competition; violence
6.  Mu-opioid receptor (OPRM1) variation, oxytocin levels and maternal attachment in free-ranging rhesus macaques 
Behavioral neuroscience  2011;125(2):131-136.
Understanding the genetic and neuroendocrine basis of the mother-infant bond is critical to understanding mammalian affiliation and attachment. Functionally similar non-synonymous mu-opioid receptor (OPRM1) SNPs have arisen and been maintained in humans (A118G) and rhesus macaques (C77G). In rhesus macaques, variation in OPRM1 predicts individual differences in infant affiliation for mothers. Specifically, infants carrying the G allele show increased distress on separation from their mothers, and spend more time with them upon reunion, than individuals homozygous for the C allele. In humans, individuals possessing the G allele report higher perceptions of emotional pain on receiving rejection by social partners. We studied maternal behavior over the course of a year among free-ranging female rhesus macaques on Cayo Santiago, Puerto Rico. We then trapped females and collected blood samples, from which we assessed OPRM1 genotype; we also collected CSF samples from which we measured oxytocin (OT) levels. We show that females possessing the G allele restrain their infants more (i.e. prevent infants from separating from them by pulling them back) than females homozygous for the C allele. Females possessing the G allele also show higher OT levels when lactating, and lower OT levels when neither lactating nor pregnant, than females homozygous for the C allele. This is the first study to demonstrate an association between OPRM1 genotype and maternal attachment for infants, and is one of the first studies of any free-ranging primate population to link functional genetic variation to behavior via potentially related neuroendocrine mechanisms.
doi:10.1037/a0022695
PMCID: PMC4018727  PMID: 21463018
mother-infant bond; opioids; oxytocin; functional genetics; attachment
7.  Effects of reproductive condition and dominance rank on cortisol responsiveness to stress in free-ranging female rhesus macaques 
American journal of primatology  2010;72(7):559-565.
The hypothalamic-pituitary-adrenal (HPA) axis modulates individuals’ physiological responses to social stress, which is an inevitable aspect of the daily lives of group-living animals. Previous nonhuman primate studies have reported that sex, age, rank and reproductive condition influence cortisol levels under stressful conditions. In this study we investigated cortisol responses to stress among 70 multiparous, free-ranging female rhesus macaques (Macaca mulatta) on the island of Cayo Santiago, PR. Plasma cortisol samples were collected in two consecutive years under similar conditions. Twenty-two females were sampled both years, and most of those females were lactating in only one of the years. Individual differences in cortisol levels were stable across years, even though reproductive condition changed for most individuals. No relationship was found between age or social rank and cortisol levels. Of the females that changed reproductive conditions, cortisol levels were higher when they were lactating than when they were cycling, and the amount of change in cortisol from cycling to lactating was greatest for low-ranking individuals. Heightened reactivity to stress during lactation may be the result of concerns about infant safety, and such concerns may be higher among low-ranking mothers than among higher ranking mothers. Psychosocial stress and hyperactivation of the HPA axis during lactation can suppress immune function and increase vulnerability to infectious diseases, thus explaining why adult females in the free-ranging rhesus macaque population on Cayo Santiago have a higher probability of mortality during the birth season than during the mating season.
doi:10.1002/ajp.20793
PMCID: PMC4013499  PMID: 20039328
reproductive condition; cortisol; rank; rhesus macaques
8.  Measuring salivary analytes from free-ranging monkeys 
Physiology & behavior  2010;101(5):601-607.
Studies of large free-ranging mammals have been revolutionized by non-invasive methods for assessing physiology, which usually involve the measurement of fecal or urinary biomarkers. However, such techniques are limited by numerous factors. To expand the range of physiological variables measurable non-invasively from free-ranging primates, we developed techniques for sampling monkey saliva by offering monkeys ropes with oral swabs sewn on the ends. We evaluated different attractants for encouraging individuals to offer samples, and proportions of individuals in different age/sex categories willing to give samples. We tested the saliva samples we obtained in three commercially available assays: cortisol, Salivary Alpha Amylase, and Secretory Immunoglobulin A. We show that habituated free-ranging rhesus macaques will give saliva samples voluntarily without training, with 100% of infants, and over 50% of adults willing to chew on collection devices. Our field methods are robust even for analytes that show poor recovery from cotton, and/or that have concentrations dependent on salivary flow rate. We validated the cortisol and SAA assays for use in rhesus macaques by showing aspects of analytical validation, such as that samples dilute linearly and in parallel to assay standards. We also found that values measured correlated with biologically meaningful characteristics of sampled individuals (age and dominance rank). The SIgA assay tested did not react to samples. Given the wide range of analytes measurable in saliva but not in feces or urine, our methods considerably improve our ability to study physiological aspects of the behavior and ecology of free-ranging primates, and are also potentially adaptable to other mammalian taxa.
doi:10.1016/j.physbeh.2010.09.003
PMCID: PMC3959823  PMID: 20837036
field methods; laboratory methods; enzyme-immuno-assay; immune function; cortisol; alpha amylase; secretory immunoglobulin A; saliva; mammalian
9.  Effects of sex and early maternal abuse on adrenocorticotropin hormone and cortisol responses to the corticotropin-releasing hormone challenge during the first 3 years of life in group-living rhesus monkeys 
In this study we investigated the development of the hypothalamic–pituitary–adrenal (HPA) axis in 21 group-living rhesus monkeys infants that were physically abused by their mothers in the first few months of life and in 21 nonabused controls. Cortisol and adrenocorticotropin hormone (ACTH) responses to a corticotropin-releasing hormone (CRH) challenge were assessed at 6-month intervals during the subjects’ first 3 years of life. Abused infants exhibited greater cortisol responses to CRH than controls across the 3 years. Abused infants also exhibited blunted ACTH secretion in response to CRH, especially at 6 months of age. Although there were no significant sex differences in abuse experienced early in life, females showed a greater cortisol response to CRH than males at all ages. There were no significant sex differences in the ACTH response to CRH, or significant interactions between sex and abuse in the ACTH or cortisol response. Our findings suggest that early parental maltreatment results in greater adrenocortical, and possibly also pituitary, responsiveness to challenges later in life. These long-term alterations in neuroendocrine function may be one the mechanisms through which infant abuse results in later psychopathologies. Our study also suggests that there are developmental sex differences in adrenal function that occur irrespective of early stressful experience. The results of this study can enhance our understanding of the long-term effects of child maltreatment as well as our knowledge of the development of the HPA axis in human and nonhuman primates.
doi:10.1017/S0954579409990253
PMCID: PMC3954978  PMID: 20102646
10.  Mother–infant interactions in free-ranging rhesus macaques: Relationships between physiological and behavioral variables 
Physiology & behavior  2008;96(0):613-619.
Studies of mother–infant relationships in nonhuman primates have increasingly attempted to understand the neuroendocrine bases of interindividual variation in mothering styles and the mechanisms through which early exposure to variable mothering styles affects infant behavioral development. In this study of free-ranging rhesus macaques on Cayo Santiago, Puerto Rico, we aimed to: 1) compare lactating and nonlactating females to investigate whether lactation is associated with changes in plasma cortisol, prolactin and oxytocin, as well as changes in CSF levels of serotonin and dopamine metabolites (5-HIAA and HVA); 2) examine the extent to which interindividual variation in maternal physiology is associated with variation in maternal behavior; 3) examine the extent to which interindividual variation in infant physiology and behavior is accounted for by variation in maternal physiology and behavior. Lactating females had higher plasma concentrations of cortisol, prolactin, and oxytocin but lower CSF concentrations of HVA than nonlactating females. Variation in maternal rejection behavior was positively correlated with variation in maternal plasma cortisol levels and in CSF 5-HIAA levels while variation in the time spent nursing and grooming was associated with maternal plasma oxytocin levels. Infants who were protected more by their mothers had higher cortisol levels than those who were protected less, while infants who were rejected more had lower CSF 5-HIAA than infants who were rejected less. Since exposure to high levels of maternal protectiveness and rejection is known to affect the offspring’s behavior and responsiveness to the environment later in life, our results are consistent with the hypothesis that these effects are mediated by long-term changes in the activity of the offspring’s HPA axis and brain serotonergic system.
doi:10.1016/j.physbeh.2008.12.016
PMCID: PMC3955190  PMID: 19150451
Maternal behavior; Infant behavior; Cortisol; Monoamine neurotransmitters; Oxytocin; Prolactin; Rhesus monkeys
11.  The endocrinology of male rhesus macaque social and reproductive status: a test of the challenge and social stress hypotheses 
Social status primarily determines male mammalian reproductive success, and hypotheses on the endocrinology of dominance have stimulated unprecedented investigation of its costs and benefits. Under the challenge hypothesis, male testosterone levels rise according to competitive need, while the social stress hypothesis predicts glucocorticoid (GC) rises in high ranking individuals during social unrest. Periods of social instability in group-living primates, primarily in baboons, provide evidence for both hypotheses, but data on social instability in seasonally-breeding species with marked social despotism but lower reproductive skew are lacking. We tested these hypotheses in seasonally-breeding rhesus macaques on Cayo Santiago, Puerto Rico. We documented male fecal GC and androgen levels over a 10 month period in relation to rank, age, natal status and group tenure length, including during a socially unstable period in which coalitions of lower-ranked males attacked higher-ranked males. Androgen but not GC levels rose during the mating season; older males had lower birth season levels but underwent a greater inter-season rise than younger males. Neither endocrine measure was related to rank except during social instability, when higher ranked individuals had higher and more variable levels of both. High ranking male targets had the highest GC levels of all males when targeted, and also had high and variable GC and androgen levels across the instability period. Our results provide evidence for both the challenge and social stress hypotheses.
doi:10.1007/s00265-012-1420-6
PMCID: PMC3950204  PMID: 24634561
challenge hypothesis; social stress; male-male competition; social status; dominance
12.  Chronic stress, allostatic load, and aging in nonhuman primates 
Development and psychopathology  2011;23(4):1187-1195.
Allostatic load is the “wear and tear” of the body resulting from the repeated activation of compensatory physiological mechanisms in response to chronic stress. Allostatic load can significantly affect the aging process and result in reduced longevity, accelerated aging, and impaired health. Although low socioeconomic status is associated with high allostatic load during aging, the effects of status-related psychosocial stress on allostatic load are often confounded by lifestyle variables. Chronic psychosocial stress associated with low dominance rank in nonhuman primates represents an excellent animal model with which to investigate allostatic load and aging in humans. Research conducted with free-ranging rhesus monkeys suggests that female reproduction can also be a source of stress and allostatic load. Female reproduction is associated with increased risk of mortality and hyperactivation of the hypothalamic–pituitary–adrenal axis. Reproduction is especially stressful and costly for aging females of low rank. Although many indicators of body condition and neuroendocrine and immune function are influenced by aging, there are marked and stable individual differences among aging females in body condition, plasma cortisol responses to stress, and cytokine responses to stress. These differences are consistent with the hypothesis that there are strong differences in chronic stress among individuals, and that allostatic load resulting from chronic stress affects health during aging. Comparisons between captive and free-ranging rhesus monkey populations may allow us to understand how differences in environmental stress and allostatic load affect rates of aging, and how these in turn translate into differences in longevity and health.
doi:10.1017/S0954579411000551
PMCID: PMC3942660  PMID: 22018089
13.  A greater decline in female facial attractiveness during middle age reflects women’s loss of reproductive value 
Facial attractiveness represents an important component of an individual’s overall attractiveness as a potential mating partner. Perceptions of facial attractiveness are expected to vary with age-related changes in health, reproductive value, and power. In this study, we investigated perceptions of facial attractiveness, power, and personality in two groups of women of pre- and post-menopausal ages (35–50 years and 51–65 years, respectively) and two corresponding groups of men. We tested three hypotheses: (1) that perceived facial attractiveness would be lower for older than for younger men and women; (2) that the age-related reduction in facial attractiveness would be greater for women than for men; and (3) that for men, there would be a larger increase in perceived power at older ages. Eighty facial stimuli were rated by 60 (30 male, 30 female) middle-aged women and men using online surveys. Our three main hypotheses were supported by the data. Consistent with sex differences in mating strategies, the greater age-related decline in female facial attractiveness was driven by male respondents, while the greater age-related increase in male perceived power was driven by female respondents. In addition, we found evidence that some personality ratings were correlated with perceived attractiveness and power ratings. The results of this study are consistent with evolutionary theory and with previous research showing that faces can provide important information about characteristics that men and women value in a potential mating partner such as their health, reproductive value, and power or possession of resources.
doi:10.3389/fpsyg.2014.00179
PMCID: PMC3938111  PMID: 24592253
facial attractiveness; middle age; sex differences; reproductive value; power; personality
14.  Relationship Status and Relationship Instability, but Not Dominance, Predict Individual Differences in Baseline Cortisol Levels 
PLoS ONE  2013;8(12):e84003.
We investigated variation in baseline cortisol levels in relation to relationship status (single or in a relationship), relationship characteristics (length, stability, presence or absence of clear dominance), or individual attributes (dominant or subordinate status, relative physical attractiveness, relationship worries). Study participants were 77 men and 75 women aged between 18 and 38 years. Individuals in romantic relationships had lower cortisol levels than singles. Individuals of African ethnicity, however, showed the opposite pattern. Individuals who perceived their relationship to be highly unstable had higher cortisol levels. Aside from African-Americans, married individuals reported the lowest relationship instability and the lowest cortisol levels, followed by individuals in long-term relationships, and by individuals in short-term relationships. The presence or absence of clear dominance in the relationship, dominance status, or relationship worries did not affect cortisol levels. Therefore relationship status and relationship instability were better predictors of variation in cortisol (presumably through stress-related mechanisms) than individual attributes.
doi:10.1371/journal.pone.0084003
PMCID: PMC3865306  PMID: 24358324
15.  Plasma cortisol responses to stress in lactating and nonlactating female rhesus macaques 
Hormones and behavior  2007;53(1):10.1016/j.yhbeh.2007.09.013.
Lactating female rats without their pups exhibit lower HPA responsiveness to stress than nonlactating females. However, responsiveness to stress is similar when lactating females are tested with their pups and the stressor involves a potential threat to the offspring. This study constitutes the first comparison of stress responsiveness in lactating and nonlactating female nonhuman primates. Subjects were 53 multiparous female free-ranging rhesus macaques. Approximately half of the females were lactating and half were nonpregnant/nonlactating. Blood samples were obtained after capture and after overnight housing in an individual cage. Lactating females were tested with their infants. Lactating females had significantly higher plasma cortisol levels than nonlactating females on both days. Having or not having an infant was also a better predictor of plasma cortisol levels among all females than their age, dominance rank, group of origin, time of day at which the sample was obtained, and time elapsed since beginning of the sampling procedure or since anesthesia. Plasma cortisol levels of lactating females were not significantly correlated with post-partum stage or with the cortisol levels of their infants. Capture, handling, and individual housing in a cage are powerful psychological stressors for free-ranging primates. We suggest that the higher plasma cortisol levels exhibited by lactating females reflect greater responsiveness to stress associated with perception of risks to infants. Hyporesponsiveness to stress may not be a general characteristic of lactation in all mammalian species, but a short-term effect of infant suckling that is most apparent with stressors unrelated to the offspring.
doi:10.1016/j.yhbeh.2007.09.013
PMCID: PMC3859185  PMID: 17963759
Responsiveness to stress; Cortisol; Lactation; Infants; Humans; Nonhuman primates
16.  Effects of Early Traumatic Experience on Vocal Expression of Emotion in Young Female Rhesus Macaques 
Developmental psychobiology  2010;52(8):10.1002/dev.20475.
The present study used a cross-fostering procedure to investigate the effects of early traumatic experience on vocal expressions of emotions in rhesus macaques (Macaca mulatta). The subjects of the study were 12 juvenile females: six were born to abusive mothers and reared by nonabusive controls, and six were born to controls and reared by abusive mothers. The cross-fostering took place within 24–48 hours after birth. Vocalizations were recorded from the subjects in their social groups during their first two years of life. Abusive mothers maltreated their adopted daughters in the first 2–3 months after birth with patterns similar to those previously shown with their biological offspring. Abused females produced proportionally more noisy screams compared to controls. While controls used noisy screams during contact aggression and tonal screams during non-contact aggression, the screams from the abused animals appeared to be distributed equally across contexts. Acoustical analyses revealed that the screams of the abused females were less modulated and had lower fundamental frequencies compared to the screams of controls. Taken together, these results suggest that traumatic experiencee in the first few months of life can have long-term effects on vocal emotional expression in rhesus macaques.
doi:10.1002/dev.20475
PMCID: PMC3859189  PMID: 20607793
rhesus macaque; maternal abuse; vocalizations; acoustical analysis; emotional expression
17.  Effects of age on cerebrospinal fluid oxytocin levels in free-ranging adult female and infant rhesus macaques 
Behavioral neuroscience  2010;124(3):10.1037/a0019576.
There is growing interest in studying oxytocin biology in the context of social functioning in human and non-human primates. Studies of human subjects are typically restricted to peripheral oxytocin assessments because opportunities to collect cerebrospinal fluid (CSF) are rare. A few studies have examined CSF oxytocin levels in captive adult primates, but none to our knowledge have been conducted under free-ranging conditions and inclusive of young infants. The main goal of the present study was to establish feasibility of quantifying CSF oxytocin levels in free-ranging adult female and infant rhesus monkeys living on the island of Cayo Santiago, Puerto Rico. CSF oxytocin levels were examined in relation to individuals’ demographic and reproductive characteristics, as well as in relation to plasma cortisol levels. CSF oxytocin concentrations ranged from 36.02 to 134.41 pg/ml in adult females (ages 7–26 years; N = 31) and 35.94 to 77.3 pg/ml in infants (ages 38–134 days; N = 17). CSF oxytocin levels were positively correlated with adult female age and negatively correlated with infant age. The former correlation was driven by reproductive status. CSF oxytocin levels were unrelated to dominance rank or plasma cortisol levels. In contrast to a previous study of plasma oxytocin concentrations in this population, CSF oxytocin levels did not differ significantly between lactating and non-lactating females. In summary, these findings: 1) provide feasibility data for examining CSF oxytocin biology in free-ranging nonhuman primates and 2) indicate that CSF oxytocin levels may be a biomarker of age-related central nervous system changes across lifespan development. Although our study did not report significant associations between CSF oxytocin levels and socially-relevant demographic variables, the relationships between CSF oxytocin levels and assessments of social functioning warrant future investigation.
doi:10.1037/a0019576
PMCID: PMC3859199  PMID: 20528088
Age; CSF; infant; cortisol; free-ranging; oxytocin; rhesus monkey
18.  Brain white matter microstructure alterations in adolescent rhesus monkeys exposed to early life stress: associations with high cortisol during infancy 
Background
Early adverse experiences, especially those involving disruption of the mother-infant relationship, are detrimental for proper socioemotional development in primates. Humans with histories of childhood maltreatment are at high risk for developing psychopathologies including depression, anxiety, substance abuse, and behavioral disorders. However, the underlying neurodevelopmental alterations are not well understood. Here we used a nonhuman primate animal model of infant maltreatment to study the long-term effects of this early life stress on brain white matter integrity during adolescence, its behavioral correlates, and the relationship with early levels of stress hormones.
Methods
Diffusion tensor imaging and tract based spatial statistics were used to investigate white matter integrity in 9 maltreated and 10 control animals during adolescence. Basal plasma cortisol levels collected at one month of age (when abuse rates were highest) were correlated with white matter integrity in regions with group differences. Total aggression was also measured and correlated with white matter integrity.
Results
We found significant reductions in white matter structural integrity (measured as fractional anisotropy) in the corpus callosum, occipital white matter, external medullary lamina, as well as in the brainstem of adolescent rhesus monkeys that experienced maternal infant maltreatment. In most regions showing fractional anisotropy reductions, opposite effects were detected in radial diffusivity, without changes in axial diffusivity, suggesting that the alterations in tract integrity likely involve reduced myelin. Moreover, in most regions showing reduced white matter integrity, this was associated with elevated plasma cortisol levels early in life, which was significantly higher in maltreated than in control infants. Reduced fractional anisotropy in occipital white matter was also associated with increased social aggression.
Conclusions
These findings highlight the long-term impact of infant maltreatment on brain white matter structural integrity, particularly in tracts involved in visual processing, emotional regulation, and somatosensory and motor integration. They also suggest a relationship between elevations in stress hormones detected in maltreated animals during infancy and long-term brain white matter structural effects.
doi:10.1186/2045-5380-3-21
PMCID: PMC3880213  PMID: 24289263
Early life stress; Adolescence; Rhesus monkeys; Diffusion tensor imaging
19.  Immune Function and HPA Axis Activity in Free-Ranging Rhesus Macaques 
Physiology & behavior  2011;104(3):507-514.
In mammals, the hypothalamic-pituitary-adrenal (HPA) axis and immune system play an important role in the maintenance of homeostasis. Dysregulation of either system resulting, for example, from psychosocial or reproductive stress increases susceptibility to disease and mortality risk, especially in aging individuals. In a study of free-ranging rhesus macaques, we examined how female age, reproductive state, social rank, and body condition influence (i) aspects of cytokine biology (plasma concentrations of interleukin-1 receptor antagonist (IL-1ra), IL-6 and IL-8), and (ii) HPA axis activity (plasma and fecal glucocorticoid levels). We also assessed individual differences in cytokine and hormone concentrations over time to determine their consistency and to investigate relations between these two indicators of physiological regulation and demand. Female monkeys showed marked increases in HPA axis activity during pregnancy and lactation, and increased circulating levels of IL-1ra with advancing age. Inter-individual differences in IL-1ra and IL-8 were consistent over successive years, suggesting that both are stable, trait-like characteristics. Furthermore, the concentrations of fecal glucocorticoid hormones in non-pregnant, non-lactating females were correlated with their plasma cortisol and IL-8 concentrations. Some individuals showed permanently elevated cytokine levels or HPA axis activity, or a combination of the two, suggesting chronic stress or disease. Our results enhance our understanding of within- and between-individual variation in cytokine levels and their relationship with glucocorticoid hormones in free-ranging primates. These findings can provide the basis for future research on stress and allostatic load in primates.
doi:10.1016/j.physbeh.2011.05.021
PMCID: PMC3133459  PMID: 21635909
rhesus macaque; cytokines; cortisol; aging; reproduction; allostatic load
20.  The Neuroendocrinology of Primate Maternal Behavior 
In nonhuman primates and humans, similar to other mammals, hormones are not strictly necessary for the expression of maternal behavior, but nevertheless influence variation in maternal responsiveness and parental behavior both within and between individuals. A growing number of correlational and experimental studies have indicated that high circulating estrogen concentrations during pregnancy increase maternal motivation and responsiveness to infant stimuli, while effects of prepartum or postpartum estrogens and progestogens on maternal behavior are less clear. Prolactin is thought to play a role in promoting paternal and alloparental care in primates, but little is known about the relationship between this hormone and maternal behavior. High circulating cortisol levels appear to enhance arousal and responsiveness to infant stimuli in young, relatively inexperienced female primates, but interfere with the expression of maternal behavior in older and more experienced mothers. Among neuropeptides and neurotransmitters, preliminary evidence indicates that oxytocin and endogenous opioids affect maternal attachment to infants, including maintenance of contact, grooming, and responses to separation. Brain serotonin affects anxiety and impulsivity, which in turn may affect maternal behaviors such as infant retrieval or rejection of infants’ attempts to make contact with the mother. Although our understanding of the neuroendocrine correlates of primate maternal behavior has grown substantially in the last two decades, very little is known about the mechanisms underlying these effects, e.g., the extent to which these mechanisms may involve changes in perception, emotion, or cognition.
doi:10.1016/j.pnpbp.2010.09.017
PMCID: PMC3072435  PMID: 20888383
parental behavior; estrogen; cortisol; prolactin; oxytocin; opioids; serotonin
21.  Identifying key features of early stressful experiences that produce stress vulnerability and resilience in primates 
This article examines the complex role of early stressful experiences in producing both vulnerability and resilience to later stress-related psychopathology in a variety of primate models of human development. Two types of models are reviewed: Parental Separation Models (e.g., isolate-rearing, peer-rearing, parental separations, and stress inoculation) and Maternal Behavior Models (e.g., foraging demands, variation in maternal style, and maternal abuse). Based on empirical evidence, it is argued that early life stress exposure does not increase adult vulnerability to stress-related psychopathology as a linear function, as is generally believed, but instead reflects a quadratic function. Features of early stress exposure including the type, duration, frequency, ecological validity, sensory modality, and developmental timing, within and between species, are identified to better understand how early stressful experiences alter neurobiological systems to produce such diverse developmental outcomes. This article concludes by identifying gaps in our current knowledge, providing directions for future research, and discussing the translational implications of these primate models for human development and psychopathology.
doi:10.1016/j.neubiorev.2010.09.003
PMCID: PMC3023826  PMID: 20851145
development; early experiences; HPA axis; maternal care; primate models; psychopathology; resilience; risk; stress inoculation; stressor; vulnerability
22.  Terminal investment and senescence in rhesus macaques (Macaca mulatta) on Cayo Santiago 
Behavioral Ecology  2010;21(5):972-978.
Long-lived iteroparous species often show aging-related changes in reproduction that may be explained by 2 non-mutually exclusive hypotheses. The terminal investment hypothesis predicts increased female reproductive effort toward the end of the life span, as individuals have little to gain by reserving effort for the future. The senescence hypothesis predicts decreased female reproductive output toward the end of the life span due to an age-related decline in body condition. Nonhuman primates are ideal organisms for testing these hypotheses, as they are long lived and produce altricial offspring heavily dependent on maternal investment. In this study, we integrated 50 years of continuous demographic records for the Cayo Santiago rhesus macaque (Macaca mulatta) population with new morphometric and behavioral data to test the senescence and terminal investment hypotheses. We examined relationships between maternal age and activity, mother and infant body condition, interbirth intervals, measures of behavioral investment in offspring, and offspring survival and fitness to test for age-associated declines in reproduction that would indicate senescence, and for age-associated increases in maternal effort that would indicate terminal investment. Compared with younger mothers, older mothers had lower body mass indices and were less active, had longer interbirth intervals, and spent more time in contact with infants, but had infants of lower masses and survival rates. Taken together, our results provide strong evidence for the occurrence of reproductive senescence in free-ranging female rhesus macaques but are also consistent with some of the predictions of the terminal investment hypothesis.
doi:10.1093/beheco/arq098
PMCID: PMC2920293  PMID: 22475990
aging; life history; maternal investment; offspring fitness; reproductive senescence; rhesus macaques
23.  Urinary C-Peptide Measurement as a Marker of Nutritional Status in Macaques 
PLoS ONE  2011;6(3):e18042.
Studies of the nutritional status of wild animals are important in a wide range of research areas such as ecology, behavioural ecology and reproductive biology. However, they have so far been strongly limited by the indirect nature of the available non-invasive tools for the measurement of individual energetic status. The measurement of urinary C-peptide (UCP), which in humans and great apes shows a close link to individual nutritional status, may be a more direct, non-invasive tool for such studies in other primates as well and possibly even in non-primate mammals. Here, we test the suitability of UCPs as markers of nutritional status in non-hominid primates, investigating relationships between UCPs and body-mass-index (BMI), skinfold fatness, and plasma C-peptide levels in captive and free-ranging macaques. We also conducted a food reduction experiment, with daily monitoring of body weight and UCP levels. UCP levels showed significant positive correlations with BMI and skinfold fatness in both captive and free-ranging animals and with plasma C-peptide levels in captive ones. In the feeding experiment, UCP levels were positively correlated with changes in body mass and were significantly lower during food reduction than during re-feeding and the pre-experimental control condition. We conclude that UCPs may be used as reliable biomarkers of body condition and nutritional status in studies of free-ranging catarrhines. Our results open exciting opportunities for energetic studies on free-ranging primates and possibly also other mammals.
doi:10.1371/journal.pone.0018042
PMCID: PMC3068145  PMID: 21479215
24.  Reading men's faces: women's mate attractiveness judgments track men's testosterone and interest in infants 
This study investigated whether women track possible cues of paternal and genetic quality in men's faces and then map perception of those cues onto mate attractiveness judgments. Men's testosterone concentrations served as a proxy for genetic quality given evidence that this hormone signals immunocompetence, and men's scores on an interest in infants test were chosen as prima facie markers of paternal quality. Women's perceptions of facial photographs of these men were in fact sensitive to these two variables: men's scores on the interest in infants test significantly predicted women's ratings of the photos for how much the men like children, and men's testosterone concentrations significantly predicted women's ratings of the men's faces for masculinity. Furthermore, men's actual and perceived affinity for children predicted women's long-term mate attractiveness judgments, while men's testosterone and perceived masculinity predicted women's short-term mate attractiveness judgments. These results suggest that women can detect facial cues of men's hormone concentrations and affinity for children, and that women use perception of these cues to form mate attractiveness judgments.
doi:10.1098/rspb.2006.3569
PMCID: PMC1635527  PMID: 16901836
face perception; mate attractiveness; testosterone; interest in infants
25.  Effects of early experience on female behavioural and reproductive development in rhesus macaques 
A growing body of research on humans suggests that exposure to a stressful family environment or father absence from home during childhood is associated with early female puberty and greater interest in infants among adolescent girls. This effect may be mediated by early exposure to harsh and inconsistent maternal care, but the mechanisms by which maternal care affects female reproductive maturation are not known. The present study reports sex differences in interest in infants among juvenile rhesus macaques similar to those observed in human adolescents. Furthermore, juvenile females that were exposed to harsh and inconsistent maternal care in infancy showed higher interest in infants than controls. Evidence from cross-fostered females indicated that these effects resulted from early experience and not genetic inheritance from the mother. There were no significant differences in female age at first conception in relation to the quality of maternal care received during infancy. Macaque females exposed to harsh and inconsistent maternal care in infancy tended to have higher cortisol responses to stress and to corticotropin-releasing hormone than controls in the first three years of life. Furthermore, females with higher cortisol responses to stress exhibited higher interest in infants. These findings suggest that some of the effects of early parental care on female reproductive maturation may be mediated by developmental changes in the activity of the hypothalamic–pituitary–adrenal axis.
doi:10.1098/rspb.2005.3059
PMCID: PMC1564110  PMID: 16024388
rhesus macaques; early experience; maternal care; female reproductive maturation; interest in infants

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