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  • Original Research Article
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Early experience and serotonin transporter gene variation interact to influence primate CNS function

Molecular Psychiatry volume 7, pages 118–122 (2002)Cite this article

Abstract

Nonhuman primates offer unique opportunities to study the effects of genes, environments, and their interaction, on physiology and complex behavior. We examined genotype and early environment contributions to CNS function in a large sample of rhesus monkeys. In humans, length variation of the serotonin (5-HT) transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR) that results in allelic variation in 5-HTT expression is associated with decreased serotonergic function and 5-HT-mediated psychopathology. We report that an analogous variation of the gene's regulatory region in monkeys interacts with early experience to affect central 5-HT functioning. Monkeys with deleterious early rearing experiences were differentiated by genotype in cerebrospinal fluid concentrations of the 5-HT metabolite, 5-hydroxyindoleacetic acid, while monkeys reared normally were not. These findings demonstrate an environment-dependent effect of the rh5-HTTLPR genotype on CNS 5-HT function and suggest nonhuman primates may provide an important avenue for investigating gene/environment interactions using candidate genes for physiological and behavioral traits.

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Notes

  1. Although there were too few subjects with the s/s and xl/l genotypes for inclusion in the statistical analysis, their data are reported for reference purposes. The z-scores for CSF 5HIAA concentrations for these individuals were: s/s (n = 2) = −0.387, −0.466; xl/l (n = 1) = −0.387.

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Acknowledgements

We thank W Airoso, A Dodson, G Flory, S Higley, A Hurley, T King, S Lindell, C Shannon, PJ Pierre, J Pushkas, T Tsai and K Zajicek for assistance. Supported by the National Institutes of Health, USA, the European Commission (BMH4-CT96–0730), and the BMBF of Germany. KPL is supported by the Hermann and Lilly Schilling Foundation. We are grateful to Dr David Goldman, S Graham and L Akhtar for support of the DNA extraction and sample collection.

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Author notes

  1. M V Linnoila: Dr Linnoila is deceased

Authors and Affiliations

  1. National Institute on Alcohol Abuse and Alcoholism, Laboratory of Clinical Studies–Primate Unit, Poolesville, 20837, MD, USA

    A J Bennett, S E Shoaf, M V Linnoila & J D Higley

  2. Department of Psychiatry and Psychotherapy, University of Wüzburg, Wüzburg, Germany

    K P Lesch & A Heils

  3. National Institute on Alcohol Abuse and Alcoholism, Laboratory of Neurogenetics, Rockville, 20837, MD, USA

    J C Long & J G Lorenz

  4. National Institute of Child Health and Human Development, Laboratory of Comparative Ethology, Poolesville, 20837, MD, USA

    M Champoux & S J Suomi

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  1. A J Bennett
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  2. K P Lesch
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Correspondence to A J Bennett.

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Bennett, A., Lesch, K., Heils, A. et al. Early experience and serotonin transporter gene variation interact to influence primate CNS function. Mol Psychiatry 7, 118–122 (2002). https://doi.org/10.1038/sj.mp.4000949

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