Gene-environment interactions and response to social intrusion in male and female rhesus macaques.
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.
Schwandt
Melanie L
ML
Laboratory of Clinical and Translational Studies, National Institutes of Health/National Institute on Alcohol Abuse and Alcoholism, Poolesville, Maryland, USA. melanies@mail.nih.gov
Lindell
Stephen G
SG
Sjöberg
Rickard L
RL
Chisholm
Kelli L
KL
Higley
J Dee
JD
Suomi
Stephen J
SJ
Heilig
Markus
M
Barr
Christina S
CS
D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000502:physiology; D005163:Factor Analysis, Statistical; D005260:Female; D005787:Gene Frequency; D007175:Impulsive Behavior / Q000235:genetics / Q000503:physiopathology; D008253:Macaca mulatta / Q000235:genetics / Q000502:physiology; D008297:Male; D008426:Maternal Deprivation; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D012737:Sex Factors; D012931:Social Environment; D013315:Stress, Psychological / Q000235:genetics* / Q000503:physiopathology*
D050486:Serotonin Plasma Membrane Transport Proteins