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Cognitive impact of genetic variation of the serotonin transporter in primates is associated with differences in brain morphology rather than serotonin neurotransmission

Molecular Psychiatry volume 15, pages 512–522 (2010)Cite this article

Abstract

A powerful convergence of genetics, neuroimaging and epidemiological research has identified the biological pathways mediating individual differences in complex behavioral processes and the related risk for disease. Orthologous genetic variation in non-human primates (NHPs) represents a unique opportunity to characterize the detailed molecular and cellular mechanisms that bias behaviorally and clinically relevant brain function. We report that a rhesus macaque orthologue of a common polymorphism of the serotonin transporter gene (rh5-HTTLPR) has strikingly similar effects on behavior and brain morphology to those in humans. Specifically, the rh5-HTTLPR (S)hort allele broadly affects cognitive choice behavior and brain morphology without observably affecting the 5-hydroxytryptamine (5-HT) transporter or 5-HT1A concentrations in vivo. Collectively, our findings indicate that 5-HTTLPR-associated behavioral effects reflect genotype-dependent biases in cortical development rather than static differences in serotonergic signaling mechanisms. Moreover, these data highlight the vast potential of NHP models in advancing our understanding of human genetic variation affecting behavior and neuropsychiatric disease liability.

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Acknowledgements

We thank Professor Robert E. Ferrell, University of Pittsburgh Graduate School of Public Health, Department of Human Genetics for genotyping. This research was supported by a NARSAD Young Investigator Award (HPJ), NIH/NIAAA 014646 (CWB) and a Merit Award from the Office of Research and Development Medical Research Service, Department of Veterans Affairs (CWB).

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Authors and Affiliations

  1. Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA

    H P Jedema, P J Gianaros, D D Kerr, S Liu, A R Hariri & C W Bradberry

  2. Department of Structural Biology, University of Pittsburgh, Pittsburgh, PA, USA

    P J Greer

  3. Department of Psychology & Neuroscience, Brigham Young University, Provo, UT, USA

    J D Higley

  4. Laboratory of Comparative Ethology, NICHD, Poolesville, MD, USA

    S J Suomi & B J Lopresti

  5. Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA

    A S Olsen, J N Porter & C W Bradberry

  6. VA Pittsburgh Health Services, Pittsburgh, PA, USA

    C W Bradberry

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  1. H P Jedema
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Jedema, H., Gianaros, P., Greer, P. et al. Cognitive impact of genetic variation of the serotonin transporter in primates is associated with differences in brain morphology rather than serotonin neurotransmission. Mol Psychiatry 15, 512–522 (2010). https://doi.org/10.1038/mp.2009.90

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