Interaction Between Serotonin Transporter Gene Variation and RearingCondition in Alcohol Preference and Consumption in Female Primates

Barr, Christina S.; Newman, Timothy K.; Lindell, Stephen G.; Shannon, Courtney; Champoux, Maribeth; Lesch, Klaus‐Peter; Suomi, Stephen J.; Goldman, David; Higley, J. Dee

doi:10.1001/archpsyc.61.11.1146

Cited by 238 publications

(191 citation statements)

References 50 publications

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“…Furthermore, the leptin data indicate that s-variant females are more responsive to the adverse effects of group formation than l/l females who become subordinate. Although we saw no genotype differences in glucocorticoid negative feedback, we hypothesize that these effects of SERT genotype are due to differences in reactivity to the social environment [20,74], perhaps the result of a disruption in 5HT regulation of central CRH circuits conferred by the short allele variant.…”

Section: Discussionmentioning

confidence: 55%

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

Jarrell¹,

Hoffman²,

Kaplan³

et al. 2008

Physiology & Behavior

109

163

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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.

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Section: Discussionmentioning

confidence: 55%

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

Jarrell¹,

Hoffman²,

Kaplan³

et al. 2008

Physiology & Behavior

109

163

View full text Add to dashboard Cite

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“…153 Evidence from animal studies also supports the 5-HTTLPR G Â E in the genesis of alcohol dependence. 8,154 On the other hand, there appears to be some degree of specificity as no G Â E was identified for generalised anxiety disorder or anxiety symptoms. 15,34 While 5-HTTLPR genotype is not reliably directly associated with depression, 151 the more severe and multiple adverse outcomes including violent suicide, 155,156 suicide attempts among alcohol-dependent subjects 157 and comorbid alcohol dependence with depression 158,159 are directly associated with 5-HTTLPR s allele loading.…”

Section: Genetic Control Of the Environmentmentioning

confidence: 99%

“…9 The less active s-allele interacts with adverse early rearing conditions (peer rearing) to result in more distress, less activity, stronger neuroendocrine responses to stress, higher consumption of alcohol and lower serotonin turnover in the central nervous system. 8,9,26,27 During peerrearing, animals homozygous for the l allele develop more socially acceptable playful behaviours but sl heterozygotes tend to become aggressive, suggesting that the ll homozygous status confers an adaptive potential for adverse environment. 28 In conclusion, the non-human primate experiments support the G Â E hypothesis by showing that the s allele is associated with a vulnerability to early life adverse circumstances leading to multiple adverse outcomes resembling human psychiatric disorders.…”

Section: Animal Modelsmentioning

confidence: 99%

“…2,3 Quantitative human population genetics studies indicate that G Â E plays a role in the development of depression. [4][5][6][7] In the last five years, G Â E involving specific gene polymorphisms has been identified in animals 8,9 and humans. [10][11][12][13] Encouragingly, replications 14,15 and a positive metaanalysis 16 indicate that measuring environment improves the reliability of genetic research.…”

Section: Introductionmentioning

confidence: 99%

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The moderation by the serotonin transporter gene of environmental adversity in the aetiology of mental illness: review and methodological analysis

2007

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“…26 Moreover, a gene Â environment interaction between 5-HTTLPR and stressful life events in the development of mood disorder and suicide attempts was observed, 27 and a gene Â environment interaction for an orthologous serotonin transporter polymorphism in the Rhesus macaque was also noted. 28 Recent studies [29][30][31] have shown that including both genotypes that affect 5-HTT transcription (i.e., 5-HTTLPR and rs25531) may help to analyze the association of 5-HTT function and liability for different psychiatric disorders more adequately.…”

Section: Introductionmentioning

confidence: 99%

Gene–gene effects on central processing of aversive stimuli

et al. 2007

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Emotional reactivity and regulation are fundamental to human behavior. As inter-individual behavioral variation is affected by a multitude of different genes, there is intense interest to investigate gene-gene effects. Functional sequence variation at two genes has been associated with response and resiliency to emotionally unpleasant stimuli. These genes are the catechol-O-methyltransferase gene (COMT Val 158 Met) and the regulatory region (5-HTTLPR) of the serotonin transporter gene. Recently, it has been proposed that 5-HTT expression is not only affected by the common S/L variant of 5-HTTLPR but also by an A to G substitution. Using functional magnetic resonance imaging, we assessed the effects of COMT Val 158 Met and both 5-HTT genotypes on brain activation by standardized affective visual stimuli (unpleasant, pleasant, and neutral) in 48 healthy subjects. Based on previous studies, the analysis of genotype effects was restricted to limbic brain areas. To determine allele-dose effects, the number of COMT Met 158 alleles (i.e., lower activity of COMT) and the number of 5-HTT low expressing alleles (S and G) was correlated with the blood oxygen level-dependent (BOLD) response to pleasant or unpleasant stimuli compared to neutral stimuli. We observed an additive effect of COMT and both 5-HTT polymorphisms, accounting for 40% of the interindividual variance in the averaged BOLD response of amygdala, hippocampal and limbic cortical regions elicited by unpleasant stimuli. Effects of 5-HTT and COMT genotypes did not affect brain processing of pleasant stimuli. These data indicate that functional brain imaging may be used to assess the interaction of multiple genes on the function of neuronal networks.

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Interaction Between Serotonin Transporter Gene Variation and RearingCondition in Alcohol Preference and Consumption in Female Primates

Abstract: These data suggest a potential interaction between serotonin transporter gene variation and early experience in vulnerability to alcoholism.

Cited by 238 publications

References 50 publications

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

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

The moderation by the serotonin transporter gene of environmental adversity in the aetiology of mental illness: review and methodological analysis

Gene–gene effects on central processing of aversive stimuli

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