Article summary with Risk, resilience, and gene x environment interactions in rhesus monkeys by Suomi - 2006

Introduction 

There are differences between all individuals in the way they respond to acute/chronic stress. Many individuals who experience traumatic events exhibit only minimal effects on their biological, psychological, and emotional functioning. However, some individuals consistently respond to even the slightest changes in their physical or social environment with profound emotional, psychological, and physiological distress that often reappears without any obvious subsequent provocation.

What factors underlie these differences in responses to stress? Are they due to individual genes, their environment, or an interaction of both? This review tries to answer those questions based on rhesus monkeys and discusses some implications of those findings.

20% of monkeys these findings are based on, that grew up in a naturalistic setting, consistently react to novel, mildly stressful social situations with unusual fearful and anxious-like behaviour, accompanied by prolonged hypothalamic-pituitary-adrenal (HPA) axis activation. 

5-10% of the monkeys growing up in the same conditions are likely to exhibit impulsive and/or inappropriate aggressive patterns of behavioural response under similar circumstances. Monkeys in the latter subgroup also show chronic deficits in serotonin metabolism. 

Development of Individual Differences in Stress Reactivity

Monkeys that grow up in a naturalistic setting spend most of their first month in intimate physical contact with their mother, establishing a strong and enduring bond between mother and infant. From the second month the infant starts to explore their immediate environment, using their mother as a secure base. Later, they spend increasing amounts of time away from their mothers and begin to establish relationships with other (same-aged) members of their social group. Through the rest of their childhood they spend any hours in active social play with these peers. Nearly every social behaviour important in adulthood is developed, practiced, and perfectured during peer play, most notably behaviours leading to successful sexual reproduction and the socialization of aggression (appears at 4-6 months of age).

Excessively aggressive and/or fearful monkeys show significant deviations from their species-normative pattern of social development. Fearful infants leave their mothers to explore their environment at a later age and exhibit low rates of exploratory behaviour later on. They seem reluctant to interact with monkeys other than their mother, resulting in less peer play. When physically separated from their mothers they will exhibit excessive behavioural distress, accompanied by higher and prolonged levels of cortisol which are predictive of differential responses to other situations later in life. 

Overly aggressive infants, especially males, typically display their aggressive tendencies initially in the context of social play with peers. They readily respond to play invitations and tend to initiate rough-and-tumble play bouts, often escalating into episodes of actual physical aggression with their play partners. Other monkeys in their social groups start avoiding most interactions with these aggressive youngsters, resulting in increased social isolation. Studies reveal a significant negative relationship between the incidence of aggression in the context of play and 5-HIAA concentrations; the most aggressive males tend to have the lowest CSP 5-HIAA levels. 

Heritability analyses have shown that individual differences in behavioural and adrenocortical response to separation have a significant genetic component, as well as that differences in CSF 5-HIAA are remarkably stable over the lifespan which are also highly heritable. 

Effects of differential social Rearing Environment

In the same rhesus monkey colony, other monkeys have been reared from birth on in the absence of any adults, but in continuous presence of same aged peers, after an initial month in the researchers’ neonatal nursery. After 6 months of peer-only (PO) rearing, infants are introduced in large social groups containing same-aged PO-reared and mother-and-same-aged(MP)-reared monkeys. Both PO- and MP-reared monkeys remained in the same group until puberty.

PO-reared monkeys quickly develop strong attachment-like bonds with each other within days after release from neonatal nursery. However, these ‘hyperattachments’ tend to be nonfunctional, largely because a peer isn’t as good as mother in providing a secure base for exploration or soothing an infant when it becomes frightened/upset. As a result, PO-reared infants tend to explore and play less compared to MP-reared infants in their first 6 months. PO-reared monkey groups also show more extreme behavioural and adrenocortical responses to social separation at 6 months of age. They display similar behavioural and serotonergic characteristics that differentiate overly aggressive MP-reared monkeys from others in their cohort. Potential reason for this is that they may experience play deprivation though they’re in continuous presence of potential playmates, as they grow older they become more aggressive, more than most of their MP-reared group members. 

Early social experiences like maternal deprivation can have significant and long-lasting effects on behavioural and biological development over and above any contributions to individual differences attributable to heritable factors. 

GxE Interactions

Rhesus monkeys have the same 5-HTT gene and functional polymorphism as humans. As a result of genotyping the monkeys from the colony, researchers have been able to search for possible GxE interactions involving differential early experience and allelic variation in the 5-HTT gene. Monkeys carrying the short allele of this gene show delayed early neurobiological development, impaired serotonin functioning, and excessive aggression, HPA reactivity and alcohol consumption as they grow up, only if they have been PO-reared, MP-reared carrying the same short allele exhibit species normative patterns. MP-reared monkeys with the same short allele consume less alcohol than their MP-reared counterparts carrying the long allele, raising the assumption that having the short allele represent a significant risk factor for PO-reared, while the opposite for MP-reared monkeys is true. Though it seems apparent that significant GxE interactions occur in monkeys and humans, the demonstration of such interactions has been largely statistical and hence subject to multiple interpretations. When talking about a good gene protecting an individual from a bad environment, MP-rearing buffers individuals carrying less efficient allele from developing the aberrant patterns shown by PO monkeys with the same allele - a good environment can protect people from carrying a bad gene from detrimental developmental outcomes.

These two competing interpretations of the same data sets are not necessarily mutually exclusive. Following the author of the article, different developmental processes representing both interpretation can take place in the same individual during the same periods of development. New research demonstrates that different maternal licking/grooming of rat pups during their second postnatal week can alter gene expression with consequences that are life-long and can be transmitted to the next generation of offspring. Given the findings, the possibility that specific early social experiences can similarly alter gene expression in primates no longer seems far-fetched. If true, this could have implications for the prevention of adverse outcomes in individuals carrying the less efficient allele of these and other ‘candidate’ genes.

Summary

Rhesus monkeys exhibit individual differences in their reactions to environmental stress like humans. Some are excessively fearful in response to changes in their environment throughout development; others are overly impulsive/aggressive. Its possibly to identify genetic and environmental factors that contribute to these different response patterns, but recent evidence suggests that GxE interactions may be at least as important in shaping individual development in this species, possibly through mechanisms by which specific aspects of the environment influence expression of certain genes at certain times of development. Lastly, because GxE interactions require genetic variation at the species level to take place, the fact that rhesus monkeys - and humans - apparently possess greater allelic variability in certain genes than other primate species may contribute to their remarkable resilience and adaptive success relative to other primates.