Polymorphisms in the serotonin reuptake transporter gene modify the consequences of social status on metabolic health in female rhesus monkeys

Abstract

Individuals vary substantially in their vulnerability to physical and psychosocial stressors. The causes of such variation in susceptibility to stress are poorly understood, but are thought to relate in part to genetic factors. The present study evaluated the extent to which polymorphisms in the gene encoding the serotonin reuptake transporter (5HTTLPR or SERT) modulated physiologic responses to the imposition of psychosocial stress (social reorganization and subordinate social status) in female rhesus monkeys. Forty females, drawn from the middle ranking genealogies of several large social groups, were reorganized into eight groups containing 5 monkeys each; four groups were comprised entirely of animals homogeneous for the long promoter variant in the SERT gene (l/l), while the other four groups had monkeys with at least one allele of the short promoter variant (l/s or s/s). Females were sequentially introduced into these new groups in random order and dominance ranks were established within several days. During the ensuing 6 weeks, dominant monkeys exhibited elevated rates of aggression while subordinates displayed high rates of submission. Notably, females with the s-variant SERT genotype, collapsed across social status positions, exhibited the highest overall rates of both aggression and submission. Although neither social status nor SERT genotype influenced morning cortisol concentrations, glucocorticoid negative feedback was reduced significantly in subordinate compared to dominant females irrespective of genotype. All animals lost weight and abdominal fat across the experiment. However, decreases were greatest in subordinates, regardless of genotype, and least in dominant females with the l/l genotype. Serum concentrations of insulin, glucose, and ghrelin decreased significantly during the group formation process, effects that were independent of genotype or social status. In contrast, social status and genotype interacted to influence changes in serum concentrations of leptin and triiodothyronine (T3), as dominant, l/l females had the highest levels while subordinate s-variant females had the lowest levels. The order in which a female was introduced to her group generally predicted her eventual social rank. However, rank was additionally predicted by pre-experimental T3 and abdominal fat values, but only in the l/l animals. While these findings must be replicated with a larger sample size, the data suggest that the s-variant SERT genotype confers increased vulnerability to the adverse effects of psychosocial stress associated with subordinate status while the l/l genotype benefits the most from the absence of stress conferred by dominant social status. These findings suggest that genetic factors modify the responses of monkeys to social subordination and perhaps other psychosocial stressors.

Single Nucleotide Polymorphisms Related to HPA Axis Reactivity

“…This effect was further modulated by gender [57] . Short allele carriers of adult female rhesus monkeys subjected to social subordination showed increased plasma cortisol levels if being subordinate [58] . Moreover, these subordinate S-allele carriers also showed decreased negative feedback in the 0.25-mg DST.…”

Genetic Influences on Behavior in Nonhuman Primates

“…There appeared to be an interaction with social status, genotype, and changes in serum concentrations of leptin and triiodiothyronine. Dominant LL-homozygote females had the highest levels while subordinate S-variant females had the lowest level (Jarrell et al 2008). Watson et al (2009) found that male rhesus Sallele carriers spent less time looking at the eye region of faces, and had larger pupil diameter when gazing at photographs of familiar highstatus males from the same cohort.…”

When the Serotonin Transporter Gene Meets Adversity: The Contribution of Animal Models to Understanding Epigenetic Mechanisms in Affective Disorders and Resilience

“…It has also been shown that in depression carriers of the short variant benefit most from social support (Brummett et al 2008), indicating that sensitivity to positive stimuli can alleviate the negative consequences of sensitivity to adverse events. In a social context, short-allele carriers display more aggressive behaviours (Schwandt et al 2010) and are characterized by an increased vulnerability to the adverse effects of psychosocial stress associated with subordinate status (Jarrell et al 2008). An analogous attentional bias in rhesus monkeys is particularly striking: The short variant of the rh5-HTTLPR has been associated with a reduction in time spent gazing at images of faces compared to non-face images, less time looking in the eye regions of faces and larger pupil diameters when gazing at photos of a high versus low status male macaques (Watson et al 2009).…”