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While non-suicidal self-injury (NSSI) occurs in the general population at a surprisingly high rate, with higher rates among certain clinical populations, its etiology is not well-understood. Consequently, the DSM-5 lists NSSI as requiring further research. This study utilizes a translational model of naturally-occurring NSSI to assess the role of early parental neglect and variation in the serotonin transporter genotype (5-HTT) in the etiology of NSSI. Subjects (N = 161) were rhesus macaques (Macaca mulatta) reared in one of three conditions (mother-reared (MR), peer-reared (PR), or surrogate peer-reared (SPR)), and classified as NSSI (n = 18) or non-NSSI (n = 143). Subjects were genotyped for 5-HTT and their behaviors were recorded during an ecologically-meaningful, stress-evoking, intruder paradigm. Two weeks prior to testing, blood samples were obtained and assayed for plasma cortisol and adrenocorticotropic hormone (ACTH) concentrations. NSSI subjects were more likely to be SPR, paralleling human studies showing that individuals that exhibit NSSI tend to have experienced abuse or neglect early in life. Results also indicated that variation in the 5-HTT genotype differentiated the NSSI subjects. NSSI subjects that were homozygous for the L allele exhibited high plasma ACTH and high rates of stress-induced stereotypies; whereas NSSI subjects with the s allele exhibited impulsive behaviors, including frequently approaching the potentially dangerous intruder, high rates of aggressive vocal threats, and more activity. These results suggest that there may be different 5-HTT genotype-mediated NSSI typologies and that both early experiences and variation in the 5-HTT genotype may be important factors in understanding the etiology of NSSI.

Temperament is an individual’s nature and is widely believed to have a heritable foundation. Few studies, however, have evaluated paternal and maternal contributions to the triadic dimensions of temperament. Rhesus monkeys are widely utilized to model genetic contributions to human development due to their close genetic-relatedness and common temperament structure, providing a powerful translational model for investigating paternal and maternal genetic influences on temperament. The temperament of rhesus monkey infants born to 19 different sires and 50 different dams was assessed during the first month of life by comparing the temperament of paternal or maternal half-siblings reared with their mothers in species-normative conditions or reared in a neonatal nursery. Factor scores from three dimensions of temperament were obtained (Orienting/Regulation, Negative Affectivity, and Surgency/Extraversion) and ANOVAs were used to assess genetic effects. For paternal half-siblings, results showed a statistically significant paternal contribution to Orienting/Regulation, Negative Affectivity, and Surgency/Extraversion factor scores. For maternal half-siblings, results showed a statistically significant contribution to Orienting/Regulation factor scores. When parsed by early rearing condition, results showed a paternal contribution Orienting/Regulation, Negative Affectivity, and Surgency/Extraversion scores for paternal half-siblings reared in the neonatal nursery, while there was only a paternal contribution to Surgency/Extraversion for paternal half-siblings reared by their mothers. There was only a maternal contribution to Orienting/Regulation for maternal half-siblings reared by their mothers. These results show that paternal and maternal contributions to temperament vary by environmental context, and that mothers may environmentally buffer their infants from paternal contributions to their temperament.

Attempts to describe the latent structure of human infant temperament have led some to suggest the existence of three major dimensions. An earlier exploratory factor analysis (EFA) supported a triadic structure of temperament in week-old rhesus monkey infants, paralleling the structure in human infants. This study sought to confirm the latent triadic structure of temperament across the first month of life in a larger sample of rhesus monkey infants (N = 668), reared by their mothers or in a neonatal nursery. A weekly behavioral assessment was obtained during the first month of life using a subset of items from the widely utilized Infant Behavioral Assessment Scale (IBAS), an instrument designed to measure temperament in infant monkeys. Using the latent constructs proposed by the earlier EFA (Orienting/Regulation, Negative Affectivity, Surgency/Extraversion), multi-group, multi-time point confirmatory factor analyses were conducted to confirm the latent temperament structure across rearing groups at each time point (weeks 1-4). Results confirm and extend those of the earlier EFA: latent Orienting/Regulation, Negative Affectivity, and Surgency/Extraversion constructs were present across the rearing groups at each time point, with the IBAS items consistently loading onto the latent factors to a similar degree across rearing groups at each time point. These findings suggest foundational evolutionary roots for the triadic structure of human infant temperament, but that its behavioral manifestations vary across maturation and rearing condition. Similarities in latent temperament structure in humans and a representative nonhuman primate highlights the potential for utilizing translational nonhuman primate models to increase understanding of human temperament.

This longitudinal study spans two generations of rhesus monkeys. First, the study investigates the effects of early rearing experiences on the maternal behavior of first-generation mothers (rates of premature infant rejection) and, second, the study investigates the effects of maternal rejection on the behavior of second-generation infants. Rhesus macaque mother-infant dyads (Macaca mulatta-N = 176) were observed twice weekly, with each session lasting 300 s. First-generation mothers were raised in one of three conditions: as mother-reared controls (MR; [n = 95]), in peer groups (PR; raised without adults but with constant access to three same-aged peers [n = 49]), or with an inanimate surrogate (SPR; raised with an inanimate fleece-covered, surrogate mother and limited daily peer-group interactions [n = 32]). Second-generation infants were all raised by their differentially reared mothers and statistically grouped into one of two groups: those that were rejected by their mothers beginning at a more-typical weaning age (controls), starting in the third month of life (n = 108), and those that were prematurely rejected, with mothers showing rejections before the third month of infant life (n = 68). Overall, PR mothers exhibited the highest rates of premature infant rejection, except for month 1 of infant life, when SPR mothers exhibited the highest rates of rejection. Intriguingly, after month 1, SPR mothers showed high rates of infant cradling and seldom rejected their infants. Independent of their mothers' early rearing environment, prematurely rejected infants displayed more aggression and passive vigilance, and were cradled and groomed less by their mothers, and there was evidence that the overall rates of rejection after the first 2 months of life had a cumulative negative effect on the developing infant. Post hoc analyses of plasma cortisol levels showed that the prematurely rejected infants had higher cortisol concentrations, suggesting a high level of stress in the prematurely rejected infants. These results suggest that maternal presence during infancy has long-term effects on a female's future maternal skills which, in turn, have intergenerational consequences for the socioemotional development of second-generation infants.

It is widely held that the central monoamine neurotransmitters modulate alcohol intake. Few studies, however, directly assess the relationship between baseline and alcohol-induced monoamine turnover, as well as the change from baseline, as predictors of alcohol intake. Using a nonhuman primate model, this study investigates baseline, alcohol-induced and alcohol-induced change in monoamine activity and their relationship with alcohol intake. Alcohol-naïve, adolescent rhesus macaques (Macaca mulatta, N = 114) were administered a standardized intravenous bolus of alcohol solution (16.8%, v/v) on two occasions, approximately 1 month apart. One month prior to and 1 h following each alcohol infusion, cisternal cerebrospinal fluid (CSF) was obtained and assayed for monoamine metabolite concentrations. Approximately 6–7 months later, subjects were allowed unfettered access to an aspartame-sweetened alcohol solution (8.4%, v/v) for 1 h/day, 5 days/week, over 5–7 weeks. Results showed strong positive correlations between baseline and post-infusion CSF monoamine metabolite concentrations, indicating a trait-like response. Low baseline and post-infusion serotonin and dopamine metabolite concentrations and a smaller change in serotonin and dopamine metabolites from one infusion to the next were associated with higher alcohol intake. Low baseline and post-infusion norepinephrine metabolite concentrations predicted high alcohol intake, but unlike the other monoamines, a greater change in norepinephrine metabolite concentrations from one infusion to the next was associated with higher alcohol intake. These findings suggest that individual differences in naturally occurring and alcohol-induced monoamine activity, as well as the change between exposures, are important modulators of initial alcohol consumption and may play a role in the risk for excessive alcohol intake.

A μ-opioid receptor (OPRM1) single-nucleotide-polymorphism, found in both humans and rhesus macaques mediates the mother-infant attachment bond. Because mothers treat their sons and daughters differently, it is somewhat surprising that the role of infant sex has not been assessed in the context of a maternal-OPRM1-genotype-by-infant-sex interaction. The present study investigates the effect of maternal-OPRM1-genotype and infant sex on mother-infant behaviors. Over the first 6 months of offspring life, mother-infant behavioral data assessing attachment quality was collected twice weekly from a large number of rhesus monkey mother-infant pairs (

A variety of studies show that parental absence early in life leads to deleterious effects on the developing CNS. This is thought to be largely because evolutionary-dependent stimuli are necessary for the appropriate postnatal development of the young brain, an effect sometimes termed the “experience-expectant brain,” with parents providing the necessary input for normative synaptic connections to develop and appropriate neuronal survival to occur. Principal among CNS systems affected by parental input are the monoamine systems. In the present study,N= 434 rhesus monkeys (233 males, 201 females) were reared in one of two conditions: as mother-reared controls (MR;n= 269) or without adults with 24-h access to same-aged peers (PR;n= 165). When subjects were six-months-old, they underwent a separation paradigm involving 4, sequential, four-day social separations from their mothers or peers, with each separation followed by three-day reunions with their mothers or their peers. Prior to the separation paradigm, baseline cisternal CSF samples were obtained, as well as at the end of each the four social separations, and after final separation, during a recovery period. CSF was assayed for concentrations of monoamine metabolites and a blood sample was genotyped for the serotonin transporter (5-HTT) genotype. Replicating earlier landmark findings, PR subjects with thesallele exhibited lower baseline concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA), when compared to PR subjects homozygous for theLallele. MR subjects were undifferentiated by genotype. PR subjects exhibited lower CSF 5-HIAA concentrations during baseline, but higher CSF 5-HIAA during social separations, when compared to MR subjects. There were rearing effects for the dopamine metabolite homovanillic acid (HVA) and for the norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG), with PR subjects showing higher HVA and lower MHPG when compared to MR subjects. These findings indicate that there are long-term deficits in the response of monoamines following early maternal absence. The results of this study confirm and extend earlier findings that early parental absence has deleterious consequences for the development of the monoamine systems, and that these consequences are modulated by the 5-HTT genotype.

Objective Adopted children tend to show an increased risk for a variety of psychopathological outcomes, even when adoption occurs at birth, which some suggest is a result of nonrandom assignment of adoptees and parents. This study uses a nonhuman primate model, in which adoptions were randomly assigned, to investigate the behavioral and physiological outcomes associated with at-birth adoption. Method Immediately following birth, rhesus monkey infants were randomly assigned to be reared by either their biological mother (n = 113) or by an unrelated, lactating, adoptive mother (n = 34). At 6 months of age, infant behavior and physiology were assessed during a stressful series of mother−infant separations. Four years later, stress-related behaviors were measured following confrontation by an unfamiliar intruder, an ecologically meaningful stressor. Results When compared to infants reared by their biological mothers, adopted infants exhibited more behavioral withdrawal and higher plasma adrenocorticotropic hormone (ACTH) concentrations in response to separation. These behavioral differences persisted 4 years later during a stressful intruder challenge, with adoptees exhibiting more behavioral withdrawal, stereotypies, and impulsive approaches of the potentially aggressive intruder. Conclusion Compared to infants reared by their biological mothers, adopted infants exhibited more behavioral inhibition, impulsivity, and higher ACTH concentrations, even when subjects were randomly assigned to be adopted or to remain with their biological mother. To the extent that these findings generalize to humans, they suggest that the overall risk for psychopathology in adopted individuals persists even after random assignment to adoption conditions.

This paper uses three decades of studies with Rhesus monkeys to investigate the intergenerational effects of early life advantage. Monkeys and their offspring were both randomly assigned to be reared together or apart from their mothers. We document significant intergenerational effects of maternal presence. We also estimate, for the first time, the intergenerational complementarity of early life advantage, where the intergenerational effects of maternal rearing are only present for offspring that were mother-reared. This finding suggests that parenting is the primary mechanism driving the intergenerational effects. Our paper demonstrates how studies of primates can inform human development.

A variety of studies show that the s-allele of the serotonin transporter genotype (5-HTT) is related to aggression. However, influences of sex and 5-HTT genotype of both subject and opponent have not received as much attention in aggression research. Using a nonhuman primate model, the present study explores differences in rates of aggression exhibited by 201 group-housed male and female rhesus monkeys (Macaca mulatta; 122 females; 79 males) exposed to an unfamiliar age- and sex-matched stranger while in the presence of other same-sex members of their social group. The study also assesses whether the rates of aggression increase when the home-cage resident, the unfamiliar stimulus animal, or both possess the short (s) allele of the 5-HTT. Results showed that, when compared to females, males exhibited higher rates of physical aggression toward the stranger, and when both the male resident and the male stranger possessed the s-allele, rates of physical aggression toward the stranger increased five-fold. Resident females also engaged in higher rates of physical aggression when they possessed the s-allele, although unlike the males, their physical aggression was directed toward familiar same-sex members of their social group. The findings of this study indicate that rates of physical aggression are modulated by 5-HTT resident and stranger suggest a role of sexual competition in the phenotype of the 5-HTT genotype. Importantly, when two males with impulse deficits, as a function of the s-allele, are placed together, rates of violence exhibited by the dyad escalate substantially.

Previous developmental research suggests that motor experience supports the development of action perception across the lifespan. However, it is still unknown when the neural mechanisms underlying action-perception coupling emerge in infancy. The goal of this study was to examine the neural correlates of action perception during the emergence of grasping abilities in newborn rhesus macaques. Neural activity, recorded via electroencephalogram (EEG), while monkeys observed grasping actions, mimed actions and means-end movements during the first (W1) and second week (W2) of life was measured. Event-related desynchronization (ERD) during action observation was computed from the EEG in the alpha and beta bands, two components of the sensorimotor mu rhythm associated with activity of the mirror neuron system (MNS). Results revealed age-related changes in the beta band, but not the alpha band, over anterior electrodes, with greater desynchronization at W2 than W1 for the observation of grasping actions. Additionally, desynchronization to observed grasping actions at W2 was associated with infants’ motor skills – measured by a separate behavioral task – such that more grasping attempts were associated to greater beta ERD. These findings suggest the emergence of an early action-perception system, that relies on motor experience, shortly after birth. Keywords: Development, Mu rhythm, ERD, Mirror neuron system, Grasping actions, Electroencephalogram

INTRODUCTION: Type 2 Alcoholism is characterized by low serotonin system functioning and has a high degree of heritability, with offspring of alcoholics often showing a reduced response to the intoxicating effects of ethanol, which is thought to be marker for future alcohol use disorders (AUDs). As such, an important aim of studies investigating the origins of AUDs is understanding the relationship between serotonin system functioning and level of intoxication. A nonhuman primate model was used to evaluate observational ratings of sensitivity to ethanol and to further investigate the relationship between central serotonin activity and behavioral response to ethanol. MATERIALS AND METHODS: Cerebrospinal fluid (CSF) concentrations of 5-hydroxyindoleacetic acid (5-HIAA) were obtained from four cohorts of alcohol-naïve, adolescent rhesus macaques (N=82, 45 females, 37 males). One to three months after the CSF sample, subjects were administered a standardized intravenous (IV) ethanol bolus (males: 2.1 g/kg body weight, females: 2.0 g/kg body weight), placed into an open top, clear Plexiglas™ chamber suspended from the ceiling, and their latency to escape was recorded as a measure of the degree of intoxication. Thereafter, subjects were rated using a Likert scale for the degree of intoxication during a 30-minute observation period. RESULTS: Our results indicate that latency to escape from the chamber was associated with intoxication ratings (p = 0.0001) following the standardized IV administration of ethanol. Low CSF 5-HIAA concentrations predicted short escape latency (p = 0.006) and were associated with low intoxication ratings (p = 0.02), indicating that low CNS serotonin functioning is related to relative insensitivity to the intoxicating effects of alcohol. DISCUSSION: Our study shows that, in monkeys exposed to alcohol for the first time, objective measures of intoxication are associated with subjective ratings for intoxication and both were associated with CSF 5-HIAA concentrations. Our data confirm and extend the finding that low CNS serotonin functioning is predictive of intrinsic low sensitivity to the intoxicating effects of ethanol.

Rank acquisition is a developmental milestone for young primates, but the processes by which primate yearlings attain social rank in the absence of the mother remain unclear. We studied 18 maternally reared yearling rhesus macaques (Macaca mulatta) that differed in their social and physical rearing environments. We found that early social experience and maternal rank, but not individual traits (weight, sex, age), predicted dominance acquisition in the new peer-only social group. Yearlings also used coalitions to reinforce the hierarchy, and social affiliation (play and grooming) was likely a product, rather than a determinant, of rank acquisition. Following relocation to a familiar environment, significant rank changes occurred indicating that familiarity with a physical environment was salient in rank acquisition. Our results add to the growing body of literature emphasizing the role of the social and physical environment on behavioral development, namely social asymmetries among peers.

Milk provides not only the building blocks for somatic development but also the hormonal signals that contribute to the biopsychological organization of the infant. Among mammals, glucocorticoids (GCs) in mother’s milk have been associated with infant temperament. This study extended prior work to investigate rhesus monkey (Macaca mulatta) mother–infant dyads (N = 34) from birth through 8 months postpartum. Regression analysis revealed that cortisol concentrations in milk during the neonatal period predicted impulsivity on a cognitive task, but not global social behaviors, months later. During this time period, sex-differentiated social behavior emerged. For female infants, milk cortisol concentrations predicted total frequency of play. Collectively, these findings support and extend the “lactational programming” hypothesis on the impact of maternal-origin hormones ingested via milk.

Quantitative data on female external genital morphology are sporadic in the primate literature, and the intraspecific and interfemale variation is especially under investigated (e.g., external clitoris length). Since in most anthropoid primate species female external genitals are relatively small and often hidden, for those species whose external clitoris is described as hypertrophic, external genital resemblance may represent a source of confusion in distinguishing the sexes at a distance. This is the case of both captive and wild tufted capuchin (Sapajus spp.) infants. We provided data on external clitoral length and investigated differences in this trait at different ages in a captive female tufted capuchin population. Since likely allometric growth describes changes in relative dimensions of parts of the body that are correlated with changes in overall size, clitoris length has been analyzed by using body weight as a covariate. We measured clitoral length by adapting a technique developed for spotted hyenas (Crocuta crocuta). Our results suggest that the small body size may be only in part responsible of the perception of long clitoris in female infants, since the clitoris is actually longer in immature females compared to adult ones and its size is inversely related to body weight. While the cross-sectional nature of these data does not allow for conclusive interpretation of the results, we tentatively suggest this phenomenon as a transient male-mimicry by immature females. Our study contributed to the description of normative data in a clitoral trait, thus providing foundation for future studies about causal mechanisms and possible adaptive function(s).

Identifying predictors of teenage alcohol use disorder (AUDs) is a major health initiative, with studies suggesting that there are distinct personality-related traits that underlie patterns of alcohol intake. As temperament is biologically based, identifiable early in life, and stable across time, it is considered the foundation of personality. As such, we hypothesized that neonatal temperament traits would predict anxiety-mediated adolescent alcohol consumption. To test this, N = 145 rhesus macaque (Macaca mulatta) infants (14 days of age), reared in a neonatal nursery (n = 82) or in a control condition with their mothers (n = 63) were assessed with a widely used standardized nonhuman primate testing battery, the Infant Behavioral Assessment Scale (IBAS), modeled after the Brazelton Neonatal Assessment Scale, evaluating visual orienting, temperament, motor maturity and, more recently, sensory sensitivity. As adolescents (3-4 years of age), these same subjects were allowed unfettered access to a sweetened-alcohol solution for 1 hr/day, 4 days/week, over 5-7 weeks. Subjects were allowed to self-administer alcohol while housed alone (n = 70) or socially in their home cage (n = 55). Linear regressions showed that alcohol intake was predicted by neonatal orienting ability (β = -.35; p = .01), state control (β = -.19; p = .04), and motor maturity (β = -.24; p = .01). Poor neonatal orienting, state control (ease of consolability), and motor maturity were associated with higher adolescent alcohol intake in rhesus monkeys. These findings suggest that neonatal temperament is predictive of patterns of adolescent alcohol intake. To the extent that these results generalize to humans, they provide evidence that early-life temperament and neurodevelopment may be important risk factors for adolescent AUDs and that the IBAS may be used as an assessment tool for identifying such risk.

Epidemiological evidence links exposure to early life adversities-such as childhood maltreatment-with impaired health and well-being in adulthood. Since these effects are usually unrecognized or untreated in childhood, preventive and remediating interventions in adults are needed. Our focus on adulthood prompted three major questions. First, does our increased understanding of mechanisms accounting for the long-term effects of early life adversities help delineate underlying dimensions that underscore key similarities and differences among these adversities? Second, can adults accurately report on adversities they experienced in childhood? Third, can we identify malleable risk processes in adulthood that might be targets for preventive intervention? Supported by the National Institute on Aging, the U.K. Economic and Social and the Biotechnology and Biological Sciences Research Councils, a network of researchers in human and animal development addressed these questions through meetings and literature review. A small number of dimensions may adequately distinguish among a range of co-occurring childhood adversities. Widely used adult ascertainments of childhood adversity are poorly related to prospective ascertainment. Strategies for preventive interventions should be aimed both at adults who were actually exposed to adversity as well as those who recall adversity, but the targeted risk processes may be different. Now is an opportune time to support research on adult interventions based on unfolding research on critical periods of sensitivity to adversity in fetal and child development, on improved understanding of risk mechanisms that may persist across the life span, and on new insights on enhancing neuroplasticity in adults. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

In humans, infants respond positively to slow, gentle stroking—processed by C-tactile (CT) nerve fibers—by showing reductions in stress and increases in eye contact, smiling, and positive vocalizations. More frequent maternal touch is linked to greater activity and connectivity strength in social brain regions, and increases children’s attention to and learning of faces. It has been theorized that touch may prime children for social interactions and set them on a path towards healthy social cognitive development. However, less is known about the effects of touch on young infants’ psychological development, especially in the newborn period, a highly sensitive period of transition with rapid growth in sensory and social processing. It remains untested whether newborns can distinguish CT-targeted touch from other types of touch, or whether there are benefits of touch for newborns’ social, emotional, or cognitive development. In the present study, we experimentally investigated the acute effects of touch in newborn monkeys, a common model for human social development. Rhesus macaques (Macaca mulatta), like humans, are highly social, have complex mother-infant interactions with frequent body contact for the first weeks of life, making them an excellent model of infant sociality. Infant monkeys in the present study were reared in a neonatal nursery, enabling control over their early environment, including all caregiver interactions. One-week-old macaque infants (N = 27) participated in three 5-minute counter-balanced caregiver interactions, all with mutual gaze: stroking head and shoulders (CT-targeted touch), stroking palms of hands and soles of feet (Non-CT touch), or no stroking (No-touch). Immediately following the interaction, infants watched social and nonsocial videos and picture arrays including faces and objects, while we tracked their visual attention with remote eye tracking. We found that, during the caregiver interactions, infants behaved differently while being touched compared to the no-touch condition, irrespective of the body part touched. Most notably, in both touch conditions, infants exhibited fewer stress-related behaviors—self-scratching, locomotion, and contact time with a comfort object—compared to when they were not touched. Following CT-targeted touch, infants were faster to orient to the picture arrays compared to the other interaction conditions, suggesting CT-targeted touch may activate or prime infants’ attentional orienting system. In the No-touch condition infants attended longer to the nonsocial compared to the social video, possibly reflecting a baseline preference for nonsocial stimuli. In contrast, in both touch conditions, infants’ looked equally to the social and nonsocial videos, suggesting that touch may influence the types of visual stimuli that hold infants’ attention. Collectively, our results reveal that newborn macaques responded positively to touch, and touch appeared to influence some aspects of their subsequent attention, although we found limited evidence that these effects are mediated by CT fibers. These findings suggest that newborn touch may broadly support infants’ psychological development, and may have early evolutionary roots, shared across primates. This study illustrates the unique insight offered by nonhuman primates for exploring early infant social touch, revealing that touch may positively affect emotional and attentional development as early as the newborn period.

OBJECTIVE Child-rearing environments have been associated with morbidity in adult rhesus monkeys. We examine whether such links are also seen with leukocyte telomere length. METHODS To determine telomere length in leukocytes, blood was collected from 11 adult female monkeys aged 7 to 10 years who had been exposed to different rearing environments between birth and 7 months. Four had been reared with their mothers in typical social groups composed of other female monkeys, their offspring, and 1 to 2 adult male monkeys. The other 7 had been reared in either small groups of peers or individual cages with extensive peer interaction daily. After 7 months, all shared a common environment. RESULTS Telomere lengths were longer for those adults who had been reared with their mothers in social groups (median = 16.0 kb, interquartile range = 16.5-15.4) than for those who were reared without their mothers (median = 14.0 kb, interquartile range = 14.3-12.7; 2.2 kb/telomere difference, p < .027). CONCLUSIONS This observation adds to emerging knowledge about early adverse child-rearing conditions and their potential for influencing later morbidity. Because newborns were randomly assigned to the mother or other rearing conditions, the findings are not confounded by other conditions that co-occur with adverse child-rearing environments in humans (e.g., prenatal stress, nutrition and health as well as postnatal nutrition and negative life experiences over and above rearing conditions).

Studies in rodents, nonhuman primates, and humans suggest that epigenetic processes mediate between early life experiences and adult phenotype. However, the normal evolution of epigenetic programs during child development, the effect of sex, and the impact of early life adversity on these trajectories are not well understood. This study mapped the genome-wide DNA methylation changes in CD3+ T lymphocytes from rhesus monkeys from postnatal day 14 through 2 years of age in both males and females and determined the impact of maternal deprivation on the DNA methylation profile. We show here that DNA methylation profiles evolve from birth to adolescence and are sex dependent. DNA methylation changes accompany imposed weaning, attenuating the difference between males and females. Maternal separation at birth alters the normal evolution of DNA methylation profiles and targets genes that are also affected by a later stage maternal separation, that is, weaning. Our results suggest that early life events dynamically interfere with the normal developmental evolution of the DNA methylation profile and that these changes are highly effected by sex.

Early life experience and socioeconomic status (SES) are well-established predictors of health outcomes in people. Both factors likely influence health outcomes via hypothalamic-pituitary-adrenal (HPA) axis regulation. However, it is unclear how early experience and HPA axis activity influence adult social status. We studied differentially reared female rhesus monkeys (Macaca mulatta, N = 90) as models to test the hypothesis that chronic HPA axis activity assessed via hair cortisol concentrations (HCCs) mediated the relationship between early life experience and adult social rank. We found that mother-peer-reared (MPR) monkeys acquired higher social ranks than either of the two nursery-reared (NR) groups (peer-reared, PR, or surrogate-peer-reared, SPR monkeys) (β = −0.07, t((89)) = −2.16, p = 0.034). We also found that MPR HCCs were lower during the juvenile period at 18 months (F(2,25) = 3.49, p = 0.047). Furthermore, for MPR but not NR monkeys, changes in HCCs from 18 to 24 months (r((s)) = −0.627, p = 0.039) and adult HCCs (r((s)) = −0.321, p = 0.03) were negatively correlated with adult social rank. These findings suggest that chronic HPA axis regulation in juvenility, and perhaps in adulthood, may influence adult social status for primates that experience typical early rearing. However, early life adversity may result in dissociation between neuroendocrine stress regulation and adult social competence, which may be risk factors for adverse health outcomes.

Highlights • Touch improves infant health, but little is known about behavioral effects of touch. • We explored the influence of neonatal social touch on rhesus macaque monkeys. • Newborns who received extra handling responded more positively to novelty. • Higher rates of touch were associated with better cognitive and social development. • Neonatal touch may broadly support infants’ development., Touch is one of the first senses to develop and one of the earliest modalities for infant-caregiver communication. While studies have explored the benefits of infant touch in terms of physical health and growth, the effects of social touch on infant behavior are relatively unexplored. Here, we investigated the influence of neonatal handling on a variety of domains, including memory, novelty seeking, and social interest, in infant monkeys (Macaca mulatta; n = 48) from 2 to 12 weeks of age. Neonates were randomly assigned to receive extra holding, with or without accompanying face-to-face interactions. Extra-handled infants, compared to standard-reared infants, exhibited less stress-related behavior and more locomotion around a novel environment, faster approach of novel objects, better working memory, and less fear towards a novel social partner. In sum, infants who received more tactile stimulation in the neonatal period subsequently demonstrated more advanced motor, social, and cognitive skills—particularly in contexts involving exploration of novelty—in the first three months of life. These data suggest that social touch may support behavioral development, offering promising possibilities for designing future early interventions, particularly for infants who are at heightened risk for social disorders.

Face-to-face interactions between mothers and infants occur in both human and non-human primates, but there is large variability in the occurrence of these behaviors and the reason for this variability remains largely unexplored. Other types of maternal investment have been shown to be dependent on infant sex (e.g. milk production and maternal responsiveness) and maternal experience (e.g. symmetrical communication). Thus, we sought to determine whether variability in face-to-face interactions, that is, mutual gazing (MG), which are hypothesized to be important for later socio-cognitive development, could be explained by these variables. We studied 28 semi-free ranging rhesus monkey (Macaca mulatta) mother-infant dyads (6 primiparous; 12 male infants) born and reared at the Laboratory of Comparative Ethology field station at the NIH Animal Center in Poolesville, MD, across the first 90 postnatal days. Infant sex (i.e. male) was a significant predictor of maternal grooming (β ± SE = 0.359 ± 0.164, Z = 2.19, P = 0.029) whereas both parity (i.e. first time mothers) and infant sex (i.e. male) significantly predicted MG (parity: β ± SE = -0.735 ± 0.223, Z = -3.30, P

Though cognitive testing of infant monkeys has been practiced for the past 40 years, these assessments have been limited primarily to nursery-reared infants due to the confounds of separating mother-reared infants for assessments. Here, we describe a pilot study in which we developed a cognitive testing apparatus for socially housed, mother-peer-reared rhesus macaques under 1 year of age (Macaca mulatta) that allowed the infants to freely return to their mothers for contact comfort. Infants aged 151.2 ± 18.3 days (mean ± SEM; n = 5) were trained and tested on an object detour reach task. Infants completed training in 5.0 ± 0.2 days, and completed testing in 6.2 ± 0.9 days. Across 4 days of testing, infants improved to nearly errorless performance (Friedman test: χ(2) = 13.27, df = 3, p = 0.004) and learned to do the task more quickly (Friedman test: χ(2) = 11.69, df = 3, p = 0.009). These are the first cognitive data in group-housed, mother-peer-reared rhesus monkeys under 1 year of age, and they underscore the utility of this apparatus for studying cognitive development in a normative population of infant monkeys.

Both human and nonhuman primate adults use infant-directed facial and vocal expressions across many contexts when interacting with infants (e.g., feeding, playing). This infant-oriented style of communication, known as infant-directed speech (IDS), seems to benefit human infants in numerous ways, including facilitating language acquisition. Given the variety of contexts in which adults use IDS, we hypothesized that IDS supports learning beyond the linguistic domain and that these benefits may extend to nonhuman primates. We exposed 2.5-month-old rhesus macaque infants (N = 15) to IDS, adult-directed speech (ADS), and a non-social control (CTR) during a video presentation of unrelated stimuli. After a 5- or 60-minute delay, infants were shown the familiar video side-by-side with a novel video. Infants exhibited a novelty preference after the 5-minute delay, but not after the 60-minute delay, in the ADS and CTR conditions, and a novelty preference in the IDS condition only after the 60-minute delay. These results are the first to suggest that exposure to IDS affects infants' long-term memory, even in non-linguistic animals.

A fundamental issue in cognitive neuroscience is how the brain encodes the actions and intentions of others. The discovery of an action-production-perception mechanism underpinning such a capacity advanced our knowledge of how these processes occur; however, no study has examined how the early postnatal environment may shape action-production-perception. Here, we examined the effects of social experience on action-production-perception in 3-day-old rhesus macaques that were raised either with or without their biological mothers. We measured the neonatal imitation skills and brain electrical activity responses, while infants produced and observed facial gestures. We hypothesized that early social experiences may shape brain activity, as assessed via electroencephalogram suppression in the α band (5-7 Hz in infants, known as the mu rhythm) during action observation, and lead to more proficient imitation skills. Consistent with this hypothesis, the infants reared by their mothers were more likely to imitate lipsmacking (LS) - a natural, affiliative gesture - and exhibited greater mu rhythm desynchronization while viewing LS gestures than the nursery-reared infants. These effects were not found in response to tongue protrusion, a meaningless gesture, or a nonsocial control. These data suggest that socially enriched early experiences in the first days after birth increase brain sensitivity to socially relevant actions. © 2015 S. Karger AG, Basel.

Neuroscience offers insight into processes that support the development of the social brain within the cultural contexts that permit attachment relationships to form. Both human and nonhuman animal studies are critical to inform theory development and hypothesis testing via descriptive and experimental studies. A scientifically valid evolutionary theory is necessary to account for the remarkable diversity of parenting systems across human and many nonhuman animals. This chapter examines the neural foundations of attachment and poses critical questions that relate to the initiation of this relationship: How does attachment interface with brain development? What is the interplay between attachment and brain development (including elements of bidirectionality)? Are there negative consequences associated with variation in attachment, and are they reversible? Rather than conceptualizing attachment in terms of a single type of relationship, or a rigid developmental channel, this chapter proposes that an expanded consideration of variation is necessary to understand the neural foundations of infant-caregiver relationships, and the role of those relationships in developing competence across the life span. This approach will permit identification of common neurobiological elements of attachment as well as the remarkable plasticity and diversity within and across individuals, cultures, and species.

Significance Epigenetically programmed stress adaptation may be a conduit for informing offspring of environmental challenge. We employed ChIP-sequencing to examine effects of early environment on epigenetic regulation using hippocampal samples from macaques exposed to disruption in maternal care. We found decreased H3K4me3 binding at genes critical to behavioral stress response, the most robust being the oxytocin receptor gene (OXTR), for which we observed a corresponding decrease in RNA expression. Post hoc analysis showed that a gain-of-function OXTR SNP rescued behavioral differences in early stress-exposed subjects. Our data suggest that epigenetic down-modulation of OXTR in brain could contribute to behavioral differences observed in early stress-exposed subjects and that functional genetic variation plays a role. These could have translational implications for human psychiatric disease and personality disorders., Adaptations to stress can occur through epigenetic processes and may be a conduit for informing offspring of environmental challenge. We employed ChIP-sequencing for H3K4me3 to examine effects of early maternal deprivation (peer-rearing, PR) in archived rhesus macaque hippocampal samples (male, n = 13). Focusing on genes with roles in stress response and behavior, we assessed the effects of rearing on H3K4me3 binding by ANOVA. We found decreased H3K4me3 binding at genes critical to behavioral stress response, the most robust being the oxytocin receptor gene OXTR, for which we observed a corresponding decrease in RNA expression. Based on this finding, we performed behavioral analyses to determine whether a gain-of-function nonsynonymous OXTR SNP interacted with early stress to influence relevant behavioral stress reactivity phenotypes (n = 194), revealing that this SNP partially rescued the PR phenotype. PR infants exhibited higher levels of separation anxiety and arousal in response to social separation, but infants carrying the alternative OXTR allele did not exhibit as great a separation response. These data indicate that the oxytocin system is involved in social-separation response and suggest that epigenetic down-modulation of OXTR could contribute to behavioral differences observed in PR animals. Epigenetic changes at OXTR may represent predictive adaptive responses that could impart readiness to respond to environmental challenge or maintain proximity to a caregiver but also contribute to behavioral pathology. Our data also demonstrate that OXTR polymorphism can permit animals to partially overcome the detrimental effects of early maternal deprivation, which could have translational implications for human psychiatric disorders.

Sociality is a fundamental aspect of human behavior and health. One benefit of affiliative social relationships is reduced short-term levels of glucocorticoids (GCs), which are indicative of physiological stress. Less is known, however, about chronic GC production in relation to affiliative social behavior. To address this issue, we studied a semi-free ranging troop of rhesus macaques ( Macaca mulatta ) and collected hair samples to measure hair cortisol concentrations (HCCs), as a measure of chronic GC production, during routine biannual exams. We collected social behavior (both aggressive and affiliative) and hair samples for 32 adult female rhesus macaques over one year (Experiment 1). Our results indicated that adult females who initiated higher levels of social affiliation had significantly lower levels of HCCs. Neither the initiation nor the receipt of aggression were significantly related to HCCs in this study. In a second experiment we studied 28 mother-infant dyads for the first 90 days postpartum to examine mother-infant facial interactions (i.e. mutual gazing). We analyzed HCCs during weaning approximately one year later, which is a major transitional period. We found that infants that engaged in higher levels of mutual gazing in the first 90 days postpartum had significantly lower levels of HCCs during weaning. Finally, we studied 17 infant rhesus macaques (13 males) to examine whether social behavior (such as play) in the first five months of life correlated with infant HCCs over those months (Experiment 3). We found that infant males that engaged in more social play had significantly lower levels of HCCs. By relying on an animal model, our study shows that affiliative social traits are associated with lower long-term GC production. Future research should address the complex interactions between social behavior, chronic GC production, and mental and physical health.

Rhesus macaques (Macaca mulatta) are gregarious primates that form despotic societies characterized by frequent and intense aggression. Within long-term social groups, demographic changes may influence hierarchical stability, potentially resulting in conflict and violently abrupt hierarchical changes. This conflict can result in serious implications for animal welfare, and thus, predictive tools would be invaluable to captive managers in determining social instabilities. Using the method Elo-rating to track rank changes and dominance stability, we predicted that demographic changes to a population of semi-free ranging rhesus macaques would result in changes in hierarchical stability. Over a 3 y period, dominance data were recorded on all troop members to track the hierarchy. Throughout the 3 y, significant changes occurred to the population (mainly due to health and colony management reasons; no changes specifically occurred for this study) including permanent removal of a large group of natal males, temporary and permanent removal of top-ranking females, and depositions of top-ranking families. Our retrospective study suggests that removing natal males was beneficial in promoting overall troop stability (that is, stability of dominance relationships), although remaining males opportunistically attempted to increase in rank, perhaps due to limited competition. Our results also suggest that removing top-ranking females, even temporarily, destabilized dominance relationships; consequently adjacently ranked females opportunistically increased in Elo-rating, both before and after the depositions of the α families. Thus, these challenges to the established hierarchy can be predicted by increases in Elo-rating within the β families after demographic changes to the α families. Our results suggest that the presence of natal males and the removal of top-ranking females should be minimized to maintain stable dominance relationships. In addition, longitudinal data reflecting dominance ranks, collected by using Elo-rating, may help managers of captive colonies in predicting dominance instabilities before they occur.

Matrilineal overthrows in macaque societies are rare but devastating events, often resulting in severe morbidity, mortality, and loss of individual and group fitness. The handful of documented macaque overthrows provides scant evidence to reveal the severity or longevity of reproductive consequences resulting from such violent events. We analyzed archival records from semi-free ranging rhesus monkeys, Macaca mulatta, across six years [55≤N≤107, from 2007–2012] during which time a matrilineal overthrow occurred [in 2009] to test the hypothesis that extremely violent interactions such as a matrilineal overthrow would significantly reduce reproductive fitness for the involved matrilines and for the troop collectively. The matrilineal overthrow resulted in a significant increase in infant loss for the population from the previous year [χ2=8.117, df=1, P=0.004], as evidenced by the fact that in 2009, but not in other years, the proportion of infants lost was greater than the proportion of viable infants [χ2=4.55, df=1, P=0.03]. Moreover, the deposed matriline suffered 100% infant loss in 2009, a significant change from the previous year [χ2=7.87, df=1, P=0.005] while the attacking matriline suffered 50% infant loss [also a significant change from the previous year; χ2=4.44, df=1, P=0.035], with the uninvolved, lowest-ranking matriline showing no change in infant loss from the previous year [χ2=0.008, df=1, P=0.93]. The deposed matriline did not produce viable offspring again until three years later. We further found that rates of severe fighting [as indicated by the number of fight wounds requiring medical treatment] were positively correlated with infant loss across the six years of the study [r[s]=0.943, P=0.005]. Our data indicate that extreme periods of intra-group conflict, such as the matrilineal overthrow, have marked short-term consequences for individual fitness, and may be extreme examples of the long-term influences that group violence exerts on the mean fitness within a primate troop.

Population density is known to influence acute measures of hypothalamic-pituitary-adrenal (HPA) axis activity in a variety of species, including fish, deer, birds, and humans. However, the effects of population density on levels of chronic stress are unknown. Given the fact that exposure to chronically elevated levels of circulating glucocorticoids results in a host of health disparities in animals and humans alike, it is important to understand how population density may impact chronic stress. We assessed hair cortisol concentrations (HCCs), which are reliable indicators of chronic HPA axis activity, in rhesus monkeys (Macaca mulatta) to determine the influence of population density on these values. In Experiment 1, we compared HCCs of monkeys living in high-density (HD; 1 monkey/0.87m(2)) and low-density (LD; 1 monkey/63.37m(2)) environments (N=236 hair samples) and found that HD monkeys exhibited higher hair cortisol across all age categories (infant, juvenile, young adult, adult, and aged) except infancy and aged (F(5)=4.240, p=0.001), for which differences were nearly significant. HD monkeys also received more severe fight wounds than LD monkeys (χ(2)=26.053, p

This study examined the long-term effects of fluoxetine administered to juvenile rhesus monkeys who, as young adults, were imaged with positron emission tomography for two serotonergic markers: serotonin transporter (SERT) and serotonin 1A (5-HT1A) receptor. An equal number of monkeys separated from their mothers at birth-an animal model of human childhood stress-were also studied.At birth, 32 male rhesus monkeys were randomly assigned to either maternal separation or normal rearing conditions. At age 2, half (N=8) of each group was randomly assigned to fluoxetine (3 mg/kg) or placebo for 1 year. To eliminate the confounding effects of residual drug in the brain, monkeys were scanned at least 1.5 years after drug discontinuation. Social interactions were assessed both during and after drug administration.Fluoxetine persistently upregulated SERT, but not 5-HT1A receptors, in both the neocortex and the hippocampus. Whole-brain voxel-wise analysis revealed that fluoxetine had a significant effect in the lateral temporal and cingulate cortices. In contrast, neither maternal separation by itself nor the rearing-by-drug interaction was significant for either marker. Fluoxetine had no significant effect on the behavioral measures.Fluoxetine administered to juvenile monkeys upregulates SERT into young adulthood. Implications regarding the efficacy or potential adverse effects of SSRIs in patients cannot be directly drawn from this study. Its purpose was to investigate effects of SSRIs on brain development in nonhuman primates using an experimental approach that randomly assigned long-term SSRI treatment or placebo.

This report reviews the scientific literature from the past several decades that focuses on nonhuman primates (NHPs) as models of neuropsychiatric disorders, including anxiety, and alcoholism. In particular, we highlight the approaches, advantages, and disadvantages of the rearing, genetic, and epigenetic methodologies behind these studies as a means of evaluating the application of these methods in assessing disorders in NHPs as models of human disease. Finally, we describe the contributions the NHP studies have made to neuropsychiatric research and areas for future research.

Previous studies suggest that about 50% of rhesus macaque infants engage in neonatal imitation of facial gestures. Here we measured whether individual differences in newborn macaques' (n = 49) visual attention may explain why some infants imitate lipsmacking (LPS) and tongue protrusion (TP) gestures. LPS imitators, but not TP imitators, looked more to a human experimenter's face and to a control stimulus compared to nonimitators (p = .017). LPS imitation was equally accurate when infants were looking at faces and when they were looking away (p = .221); TP imitation was more accurate when infants were looking at faces (p = .001). Potentially, less attention is necessary for LPS imitation compared to TP imitation, as LPS is part of macaques' natural communicative repertoire. These findings suggest that facial gestures may differentially engage imitators and nonimitators, and infants' visual attention during neonatal assessments may uncover the conditions that support this skill.

Faces are visually attractive to both human and nonhuman primates. Human neonates are thought to have a broad template for faces at birth and prefer face-like to non-face-like stimuli. To better compare developmental trajectories of face processing phylogenetically, here, we investigated preferences for face-like stimuli in infant rhesus macaques using photographs of real faces. We presented infant macaques aged 15–25 days with human, macaque and abstract faces with both normal and linear arrangements of facial features and measured infants' gaze durations, number of fixations and latency to look to each face using eye-tracking technology. There was an overall preference for normal over linear facial arrangements for abstract and monkey faces but not human faces. Moreover, infant macaques looked less at monkey faces than at abstract or human faces. These results suggest that species and facial configurations affect face processing in infant macaques, and we discuss potential explanations for these findings. Further, carefully controlled studies are required to ascertain whether infant macaques' face template can be considered as broad as human infants' face template. Copyright © 2013 John Wiley & Sons, Ltd.

Empirical studies are incompatible with the proposal that neonatal imitation is arousal driven or declining with age. Nonhuman primate studies reveal a functioning brain mirror system from birth, developmental continuity in imitation and later sociability, and the malleability of neonatal imitation, shaped by the early environment. A narrow focus on arousal effects and reflexes may grossly underestimate neonatal capacities.

Escalation of voluntary alcohol drinking is characteristic of alcohol addiction and can be induced in rodents using intermittent access to alcohol. This model has been used to evaluate candidate therapeutics, but key systems involved in the transition into alcohol addiction, such as CRF, differ in their organization between rodents and primates. We examined the ability of an intermittent access schedule to induce escalation of voluntary alcohol drinking in non-human primates and used this model to assess the role of corticotropin releasing hormone (CRF) signaling in this process.Four young adult male rhesus macaques were given access to an 8.4% alcohol solution every other weekday (EOD; M, W, F), while four other young adult males were given the same solution every weekday (ED; M-F). Subjects were then administered a CRF1 antagonist, antalarmin.EOD increased alcohol intake by up to 50% over baseline, with a more pronounced increase immediately following reintroduction of alcohol. For the morning/daytime sessions, EOD subjects increased their consumption by 83% over baseline. Differences between ED and EOD schedules emerged quickly, and EOD-induced escalation resulted in pharmacologically active BAC's. EOD-induced alcohol consumption was insensitive to CRFR1 blockade by antalarmin, but subjects with high CSF levels of CRF were more responsive.Similar to what has been observed in rodents, intermittent access results in an escalation of voluntary alcohol drinking in non-human primates. In contrast to findings in rats, recruitment of the CRF system does not seem to be involved in the escalated alcohol drinking observed under these conditions, though individual differences in CRF system activity may play a role.