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

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

Prenatal Relocation Stress Enhances Resilience Under Challenge in Infant Rhesus Macaques.

The prenatal period is a developmental stage of peak sensitivity, during which environmental exposures can program post-natal developmental outcomes. Prenatal stress, in particular, has often been associated with detrimental neurobehavioral outcomes like mood and anxiety disorders. In the present study, we examined the effects of a stressful prenatal maternal experience (maternal relocation during pregnancy) on the post-partum development of offspring in rhesus macaques. To help isolate the effects of prenatal stress from genetic predispositions and post-natal experience, we compared biologically reared infants (infants raised with their biological mothers) with cross-fostered infants (those raised by non-related females in new social groups). We examined the effects of prenatal relocation stress on measures collected at 3-4 months of age during a standardized biobehavioral assessment. Unexpectedly, we found that prenatal stress resulted in a behavioral pattern consistent with resilience rather than anxiety: prenatal stress was linked with greater activity, lower anxiety, and more interaction with novel objects, as well as higher ratings of temperamental confidence during assessment. These effects were observed in infants reared by biological mothers as well as cross-fostered infants, suggesting that the effects of prenatal stress were not attributable to maternal genetics or post-natal factors. Our surprising results suggest that prenatal relocation stress may confer resilience in infant rhesus monkeys

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

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