Paternal early experiences influence infant development through non-social mechanisms in Rhesus Macaques.

BackgroundEarly experiences influence the developing organism, with lifelong and potentially adaptive consequences. It has recently become clear that the effects of early experiences are not limited to the exposed generation, but can influence physiological and behavioral traits in the next generation. Mechanisms of transgenerational effects of parental early experiences on offspring development are often attributed to prenatal or postnatal parental influence, but recent data suggest that germ-line plasticity may also play a role in the transgenerational effects of early experiences. These non-genetic transgenerational effects are a potentially important developmental and evolutionary force, but the effects of parental experiences on behavior and physiology are not well understood in socially complex primates. In the non-human primate, the rhesus macaque, nursery rearing (NR) is an early life manipulation used for colony management purposes, and involves separating infants from parents early in life. We examined the effects of maternal and paternal early NR on infant rhesus macaque immunity, physiology, and behavior.ResultsWe theorized that differences in behavior or physiology in the absence of parent-offspring social contact would point to biological and perhaps germ-line, rather than social, mechanisms of effect. Thus, all subjects were themselves NR. Male and female infant rhesus macaques (N= 206) were separated from parents and social groups in the first four days of life to undergo NR. These infants differed only in their degree of NR ancestry - whether their dams or sires were themselves NR. At 3-4 months of age, infants underwent a standardized biobehavioral assessment. Factors describing immunity, plasma cortisol, and emotion regulation were generated from these data using factor analysis. Paternal, but not maternal, NR was associated with greater emotionality and higher plasma cortisol, compared with infants born to CONTROL reared fathers.ConclusionsThese data suggest that macaque biobehavioral makeup is strongly influenced by paternal experiences, and via non-social mechanisms

Early Social Stress Promotes Inflammation and Disease Risk in Rhesus Monkeys.

Early social stress has potent lifelong health effects. We examined the association of early stress in the attachment relationship (low maternal sensitivity, low MS), lower maternal social hierarchy rank, and greater frequency of group-level social conflict, with biomarkers of inflammatory stress response in plasma (IL-8, MCP-1 and CRP collected two hours after temporary separation from mothers and social groups) and risk for developing a common macaques disease outcome (infectious colitis) in 170 socially-housed rhesus monkeys. We controlled for gene-environment correlations by comparing cross-fostered subjects with infants reared by their biological mothers. Low MS predicted higher levels of pro-inflammatory cytokines and proteins at 3-4 months of age (F(3, 162) = 3.508, p = 0.002, partial eta2 = 0.061) and higher lifetime risk for developing colitis for up to twelve years of age (chi square = 5.919, p = 0.026). Lower maternal social rank (F (3, 162) = 3.789, p = 0.012, partial eta2 = 0.06) and higher rates of social conflict (F (3, 162) = 4.264, p = 0.006, partial eta2 = 0.074) each also predicted greater inflammation in infancy, but not lifetime colitis risk (both p > 0.05). The effects of low MS, lower social rank, and higher social conflict were significant in infants reared by biological mothers and cross-fostered infants, suggesting that our results did not arise from gene-environment correlations, but environmental stressors alone. We conclude that several types of early social stress confer risk for inflammation in infancy, but that stress in the mother-infant relationship may confer the longest-term risk for adverse health outcomes

Decoupling social status and status certainty effects on health in macaques: a network approach.

BackgroundAlthough a wealth of literature points to the importance of social factors on health, a detailed understanding of the complex interplay between social and biological systems is lacking. Social status is one aspect of social life that is made up of multiple structural (humans: income, education; animals: mating system, dominance rank) and relational components (perceived social status, dominance interactions). In a nonhuman primate model we use novel network techniques to decouple two components of social status, dominance rank (a commonly used measure of social status in animal models) and dominance certainty (the relative certainty vs. ambiguity of an individual's status), allowing for a more complex examination of how social status impacts health.MethodsBehavioral observations were conducted on three outdoor captive groups of rhesus macaques (N = 252 subjects). Subjects' general physical health (diarrhea) was assessed twice weekly, and blood was drawn once to assess biomarkers of inflammation (interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP)).ResultsDominance rank alone did not fully account for the complex way that social status exerted its effect on health. Instead, dominance certainty modified the impact of rank on biomarkers of inflammation. Specifically, high-ranked animals with more ambiguous status relationships had higher levels of inflammation than low-ranked animals, whereas little effect of rank was seen for animals with more certain status relationships. The impact of status on physical health was more straightforward: individuals with more ambiguous status relationships had more frequent diarrhea; there was marginal evidence that high-ranked animals had less frequent diarrhea.DiscussionSocial status has a complex and multi-faceted impact on individual health. Our work suggests an important role of uncertainty in one's social status in status-health research. This work also suggests that in order to fully explore the mechanisms for how social life influences health, more complex metrics of social systems and their dynamics are needed

Sex Differences in Rhesus Monkeys’ Digit Ratio (2D:4D Ratio) and Its Association With Maternal Social Dominance Rank

Prenatal androgen exposure (PAE) plays a pivotal role in masculinizing the developing body and brain, and extreme exposure may contribute to autism, anxiety disorder and schizophrenia. One commonly used biomarker for PAE is the pointer-to-ring-finger digit length (2D:4D) ratio. Although this biomarker is widely used in human studies, relatively few studies have investigated 2D:4D ratio in nonhuman primates, particularly rhesus macaques (Macaca mulatta), one of the most commonly used animals in biomedical research. Thus far, data suggest that sexual dimorphism in 2D:4D ratio may be in the opposite direction in some monkey species, when compared to the pattern exhibited by humans and great apes. Using a large sample size, we investigated whether rhesus monkeys’ 2D:4D ratio shows the same sex-differentiated pattern present in other Old World monkey species. We also investigated whether individual differences in 2D:4D ratio are associated with the social dominance rank of subjects’ mothers during pregnancy, and the social dominance rank the subjects attained as adults. Subjects were 335 rhesus monkeys between 3 years and 24 years of age (M = 6.6). Maternal dominance rank during pregnancy and subjects’ adult dominance rank were categorized into tertiles (high, middle and low). Results showed that, across both hands, male rhesus monkeys exhibited higher 2D:4D ratio than females, a pattern consistent with other monkey species and a reversal from the pattern typically observed in humans and apes. This sex difference was modulated by maternal dominance rank, with female offspring of high-ranking and middle-ranking mothers exhibiting masculinized 2D:4D ratio, indicating that maternal dominance rank during pregnancy may influence levels of PAE. There was no association between subjects’ 2D:4D ratio and the social dominance rank they attained as adults. These findings show a consistent sex difference in Old World monkeys’ 2D:4D ratio that diverges from the pattern observed in apes and humans, and suggest maternal social dominance rank modulates PAE in rhesus monkeys

Cortisol in mother’s milk across lactation reflects maternal life history and predicts infant temperament

The maternal environment exerts important influences on offspring mass/growth, metabolism, reproduction, neurobiology, immune function, and behavior among birds, insects, reptiles, fish, and mammals. For mammals, mother’s milk is an important physiological pathway for nutrient transfer and glucocorticoid signaling that potentially influences offspring growth and behavioral phenotype. Glucocorticoids in mother’s milk have been associated with offspring behavioral phenotype in several mammals, but studies have been handicapped by not simultaneously evaluating milk energy density and yield. This is problematic as milk glucocorticoids and nutrients likely have simultaneous effects on offspring phenotype. We investigated mother’s milk and infant temperament and growth in a cohort of rhesus macaque (Macaca mulatta) mother–infant dyads at the California National Primate Research Center (N = 108). Glucocorticoids in mother’s milk, independent of available milk energy, predicted a more Nervous, less Confident temperament in both sons and daughters. We additionally found sex differences in the windows of sensitivity and the magnitude of sensitivity to maternal-origin glucocorticoids. Lower parity mothers produced milk with higher cortisol concentrations. Lastly, higher cortisol concentrations in milk were associated with greater infant weight gain across time. Taken together, these results suggest that mothers with fewer somatic resources, even in captivity, may be “programming” through cortisol signaling, behaviorally cautious offspring that prioritize growth. Glucocorticoids ingested through milk may importantly contribute to the assimilation of available milk energy, development of temperament, and orchestrate, in part, the allocation of maternal milk energy between growth and behavioral phenotype

Early predictors of impaired social functioning in male rhesus macaques (Macaca mulatta)

Autism spectrum disorder (ASD) is characterized by social cognition impairments but its basic disease mechanisms remain poorly understood. Progress has been impeded by the absence of animal models that manifest behavioral phenotypes relevant to ASD. Rhesus monkeys are an ideal model organism to address this barrier to progress. Like humans, rhesus monkeys are highly social, possess complex social cognition abilities, and exhibit pronounced individual differences in social functioning. Moreover, we have previously shown that Low-Social (LS) vs. High-Social (HS) adult male monkeys exhibit lower social motivation and poorer social skills. It is not known, however, when these social deficits first emerge. The goals of this study were to test whether juvenile LS and HS monkeys differed as infants in their ability to process social information, and whether infant social abilities predicted later social classification (i.e., LS vs. HS), in order to facilitate earlier identification of monkeys at risk for poor social outcomes. Social classification was determined for N = 25 LS and N = 25 HS male monkeys that were 1–4 years of age. As part of a colony-wide assessment, these monkeys had previously undergone, as infants, tests of face recognition memory and the ability to respond appropriately to conspecific social signals. Monkeys later identified as LS vs. HS showed impairments in recognizing familiar vs. novel faces and in the species-typical adaptive ability to gaze avert to scenes of conspecific aggression. Additionally, multivariate logistic regression using infant social ability measures perfectly predicted later social classification of all N = 50 monkeys. These findings suggest that an early capacity to process important social information may account for differences in rhesus monkeys’ motivation and competence to establish and maintain social relationships later in life. Further development of this model will facilitate identification of novel biological targets for intervention to improve social outcomes in at-risk young monkeys