Erin L. Kinnally

What is an “Adverse” Environment? Interactions of Rearing Experiences and MAOA Genotype in Rhesus Monkeys

BACKGROUND Studies have been inconsistent in demonstrating that early adversity and specific genotype can be joint risk factors for poor behavioral outcomes. Using a rhesus monkey model, we examined how social context and different forms of early adversity influence whether a specific genotype (polymorphism in the promoter region of monoamine oxidase A [MAOA]) affects display of aggressive, fearful, and anxious behaviors. METHODS Rhesus monkey infants (n = 473) were exposed to brief social challenge at age 3-4 months. Infants were reared 1) with mothers and up to 150 other animals in large cages; 2) with mothers in smaller social groups; 3) with mother and access to, at most, one other mother-infant pair; and 4) without mother but with access to a same-age peer in a nursery. RESULTS No effects of genotype were found for infants reared by mothers in large social cages, although several genotype by rearing environment interactions were evident. Animals reared in smaller social groups were more likely to display aggression, which was especially true of animals possessing the low-activity MAOA genotype. In addition, animals with low-activity genotypes that had experienced restricted mother rearing showed more anxious behavior (scratch, yawn). CONCLUSIONS Among mother-reared animals, broader contextual features, associated with the social environment and experience of the mother, can affect the extent to which genotype contributes to behavioral expression under conditions of challenge. Results also suggest that different forms of early adverse experience can affect the types of responses displayed by animals of different genotypes.

Effects of early experience and genotype on serotonin transporter regulation in infant rhesus macaques

The moderating effect of early experience on gene‐behavior associations has been well characterized. The molecular events that allow for such moderation are not well understood, however. We assessed the impact of early experience and serotonin transporter linked promoter polymorphism (rh5‐HTTLPR) genotype on peripheral serotonin transporter (5‐HTT) regulation in response to a maternal/social separation and relocation stressor in infant rhesus macaques. We further tested the hypothesis that modulation of 5‐HTT regulation by rearing and/or genotype is mediated by glucocorticoid (GC) availability. Fifty‐three infant (3–4 months of age) rhesus macaques that were either nursery reared (NR) or mother reared (MR) were genotyped for rh5‐HTTLPR. Infants were blood sampled within 2.5 h of maternal or social separation/relocation and again 5 h later. Infants were then administered dexamethasone, a synthetic GC and blood sampled 16.5 h later. 5‐HTT RNA was quantified from peripheral blood mononuclear cells. Plasma cortisol was measured at all time points. The MR individuals upregulated 5‐HTT significantly during maternal/social separation, while NR individuals did not. Concomitant increases in cortisol were not observed, but dexamethasone treatment stimulated 5‐HTT expression regardless of genotype/rearing group, and 5‐HTT expression in the post‐stressor sample was correlated with plasma cortisol levels at all time points. Our data indicate that early experience exerted a strong influence on 5‐HTT regulation during a stressor in infant rhesus macaques independent of rh5‐HTTLPR genotype. We also showed that GCs may stimulate 5‐HTT expression but that there likely exist faster‐acting transcriptional regulators of 5‐HTT that are in place as a function of experience.

Transgenerational Effects of Variable Foraging Demand Stress in Female Bonnet Macaques

Stress coping is an important part of mammalian life, influencing somatic and mental health, social integration, and reproductive success. The experience of early psychological stress helps shape lifelong stress coping strategies. Recent studies have shown that the effects of early stress may not be restricted to the affected generation, but may also be transmitted to offspring. Understanding whether early stress influences development in subsequent generations may help us understand somewhat why many stress‐related traits and diseases, for which little genetic basis has been discovered, run in families. Experimental early life “variable foraging demand” (VFD) stress has been associated with behavioral hypo‐responsiveness to stress in infant and adolescent bonnet macaques. The present study examined the behavioral effects of experimental early VFD stress in adult bonnet macaques, and further investigated whether non‐exposed adolescent offspring of VFD macaques were also affected. Thirty female bonnet macaques from four rearing histories were observed for behavioral response during stress: adults which had been VFD reared as infants (n = 11), adults which had been Control reared as infants (n = 9), and foraging demand naïve adolescents whose mothers were VFD (n = 4) or Control reared (n = 6). Subjects were observed for behavioral response during two experimental stressor conditions, including: (1) relocation to a novel environment; and (2) relocation with exposure to a “human intruder” making eye contact. Factor analysis yielded five factors that described categories of behavior across stress conditions. While adult VFD and Control reared females unexpectedly did not differ significantly, non‐exposed adolescent offspring of VFD reared mothers displayed significant hypo‐responsiveness in all behavioral categories compared with non‐exposed adolescent offspring of Control females. We suggest that stress hypo‐responsiveness previously observed in adolescent VFD reared animals may abate with age, but is nonetheless observed in the next generation. We conclude that VFD stress affects behavioral development of subsequent generations in non‐human primates. Am. J. Primatol. 75:509‐517, 2013.

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.

Genome–Environment Coordination in Neurobehavioral Development

How do we become who we are? Are we tabula rasa, blank slates randomly scrambling for imprintation of information, or are we merely the constructions of our selfish genetic blueprints? Current scientific philosophy tells us we are neither preprogrammed nor do we possess unadulterated free will. While mammalian neurobehavioral development is biologically constrained, it is also sensitive to experience. Neurophysiological patterning guides motivation and emotion that we use to navigate our environments. Our environments, however, often present unexpected challenges. We develop our strategies for responding to stress throughout prenatal and postnatal development. How does this neurobehavioral development unfold? It proceeds according to exceedingly elegant and precisely timed interactions between the genome and the environment. These interactions begin at conception and may last a lifetime but may be particularly potent at critical periods in development. During these critical periods of embryonic and early postnatal development, even the slightest variability in the coordination between the genome and the environment results in some of the breathtaking neurobehavioral variability in stress adaptation we observe in infant mammals. This chapter will examine some examples of genome– environment coordination that impacts prenatal and early postnatal neurobehavioral development in nonhuman primates. I will discuss how certain regions of the genome may put individuals at risk for disadvantageous neurobehavioral development following early stress and possible mechanisms for how this risk may occur. Next I will introduce the reader to the diverse role of epigenetics in the effects of early environment. Finally, I will consider the potential consequences of gene–environment coordination across generations. The goal of this chapter is to provide examples of the complexity of the inheritance and development of stress response strategies and to highlight new avenues for understanding why some nonhuman primates wither when challenged, while others thrive.

Enhancing genotyping of MAOA-LPR and 5-HTT-LPR in rhesus macaques (Macaca mulatta)

Genetic variation in monoamine oxidase A (MAOA) and serotonin transporter (5‐HTT)‐linked polymorphic regions (LPR) is associated with neuropsychiatric behavior.

Imitation Predicts Social Favor in Adolescent Rhesus Macaques (Macaca mulatta)

Objectives Imitation is a highly conserved component of animal behavior with multifaceted connections to sociality across taxa. One intriguing consequence of imitation in primates is that it promotes positive social feedback from the imitated toward the imitator. This suggests that imitation in primates may facilitate positive social interactions, but few studies have tracked imitation in socially housed primates. Here, we designed a novel ethogram to characterize imitation between conspecifics, to better understand whether imitation is associated with affiliation between primates in a semi-natural setting. Materials and Methods In this study, 15 juvenile rhesus macaques (Macaca mulatta) were observed at the California National Primate Research Center. Using focal sampling, frequencies of imitative events (e.g. following, postural mimicry, etc.) by the focal were observed over a course of 12 weeks. In separate observations, focal social behavior (e.g. aggression, play, etc.) was also observed. Results Subjects that exhibited higher degrees of imitation were not necessarily more prosocial, but, consistent with our hypothesis, they received significantly more play overtures from social partners (p<.01). In addition, imitation rates generally decrease with age. Conclusions Together, these results suggest that imitation is associated with receiving positive social behavior in a complex, semi-natural setting in primates, and that imitation may be more common in adolescence as opposed to adulthood. These preliminary results in a small sample set represent an important step in characterizing imitation in context of social interactions during development. Tracking these behaviors over time will elucidate whether imitation is directly recruiting these positive social interactions, as has been demonstrated in captivity.