Gene-environment interactions and response to social intrusion in male and female rhesus macaques

Abstract

Background: Genetic factors interact with environmental stressors to moderate risk for human psychopathology, but sex may also be an important mediating factor. Different strategies for coping with environmental stressors have evolved in males and females, and these differences may underlie the differential prevalence of certain types of psychopathology in the two sexes. In this study, we investigated the possibility of sex-specific gene-environment interactions in a nonhuman primate model of response to social threat.

Methods: Rhesus macaques (77 males and 106 females) were exposed to an unfamiliar conspecific. Using factor analysis, we identified three behavioral factors characterizing the response to social threat. Monkeys were genotyped for the serotonin transporter-linked polymorphism (5-HTTLPR), and the effects of genotype, early life stress, and sex on behavioral responses were evaluated.

Results: Factor analysis produced five factors: High-Risk Aggression, Impulsivity/Novelty-Seeking, Gregariousness/Boldness, Harm Avoidance, and Redirected Aggression. Overall, males displayed higher levels of High-Risk Aggression and Gregariousness/Boldness than females. Levels of High-Risk Aggression in males carrying the s allele were significantly higher if they were also exposed to early adversity in the form of peer rearing.

Conclusions: Our findings support those from studies in humans suggesting that males are more vulnerable to externalizing or aggression-related disorders. The results highlight the importance of interactions that exist among behavior, genes, and the environment and suggest that sex differences in vulnerability to psychopathology may be grounded in our evolutionary history.

Figure 1

Age and sex effects on behavioral responses to social intrusion. The bars depict least square means and standard errors (# indicates a significant main effect after Bonferroni correction from the analysis of variance, and * indicates a significant difference at p < .05 using Fisher's least significant difference post hoc tests). (A) High-risk Aggression factor. (B) Gregariousness/Boldness, characterized by spending time in social contact with the intruder animal. (C) Harm Avoidance.

Figure 2

Age and sex effects on the individual behavioral components contributing to the High-Risk Aggression factor. The bars depict least square means and standard errors (# indicates a significant main effect after Bonferroni correction from the analysis of variance, and * indicates a significant difference at p < .05 using Fisher's least significant difference post hoc tests). (A) Contact aggression by the test subject to the intruder. In addition to the sex difference indicated in the graph, there was also a main effect of age, with adults displaying more contact aggression than subadults. (B) Receive contact aggression from the intruder. In addition to the sex difference indicated in the graph, there was also a main effect of age, with adults receiving more contact aggression from the intruder than subadults. (C) Receive noncontact aggression from the intruder.

Figure 3

Interaction of genotype and rearing condition on aggressive responses to social intrusion in male rhesus macaques. The bars depict least square means (adjusted for the covariate, age) and standard errors (# indicates a significant main effect after Bonferroni correction from the analysis of variance, and * indicates a significant difference at p < .05 using Fisher's least significant difference post hoc tests). (A) High-Risk Aggression factor. (B) Contact aggression by the test subject to the intruder. (C) Receive contact aggression from the intruder. (D) Receive noncontact aggression from the intruder. Although the graph appears to indicate an interaction of rearing condition and genotype, this effect was not significant after the Bonferroni correction for multiple testing (see Table 3). In addition to the main effect of rearing condition depicted in the graph, there was a main effect of genotype, with l/s subjects receiving more noncontact aggression from the intruder than l/l subjects. MR, mother-reared; NR, nursery-reared.