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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.

Publication ,  Journal Article
Jedema, HP; Gianaros, PJ; Greer, PJ; Kerr, DD; Liu, S; Higley, JD; Suomi, SJ; Olsen, AS; Porter, JN; Lopresti, BJ; Hariri, AR; Bradberry, CW
Published in: Molecular psychiatry
May 2010

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-HT(1A) 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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Published In

Molecular psychiatry

DOI

EISSN

1476-5578

ISSN

1359-4184

Publication Date

May 2010

Volume

15

Issue

5

Start / End Page

512 / 446

Related Subject Headings

  • Tritium
  • Time Factors
  • Synaptic Transmission
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin
  • Receptor, Serotonin, 5-HT1A
  • Pyridines
  • Psychiatry
  • Protein Binding
  • Positron-Emission Tomography
 

Citation

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Jedema, H. P., Gianaros, P. J., Greer, P. J., Kerr, D. D., Liu, S., Higley, J. D., … Bradberry, C. W. (2010). Cognitive impact of genetic variation of the serotonin transporter in primates is associated with differences in brain morphology rather than serotonin neurotransmission. Molecular Psychiatry, 15(5), 512–446. https://doi.org/10.1038/mp.2009.90
Jedema, H. P., P. J. Gianaros, P. J. Greer, D. D. Kerr, S. Liu, J. D. Higley, S. J. Suomi, et al. “Cognitive impact of genetic variation of the serotonin transporter in primates is associated with differences in brain morphology rather than serotonin neurotransmission.Molecular Psychiatry 15, no. 5 (May 2010): 512–446. https://doi.org/10.1038/mp.2009.90.
Jedema HP, Gianaros PJ, Greer PJ, Kerr DD, Liu S, Higley JD, et al. Cognitive impact of genetic variation of the serotonin transporter in primates is associated with differences in brain morphology rather than serotonin neurotransmission. Molecular psychiatry. 2010 May;15(5):512–446.
Jedema, H. 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.Molecular Psychiatry, vol. 15, no. 5, May 2010, pp. 512–446. Epmc, doi:10.1038/mp.2009.90.
Jedema HP, Gianaros PJ, Greer PJ, Kerr DD, Liu S, Higley JD, Suomi SJ, Olsen AS, Porter JN, Lopresti BJ, Hariri AR, Bradberry CW. Cognitive impact of genetic variation of the serotonin transporter in primates is associated with differences in brain morphology rather than serotonin neurotransmission. Molecular psychiatry. 2010 May;15(5):512–446.

Published In

Molecular psychiatry

DOI

EISSN

1476-5578

ISSN

1359-4184

Publication Date

May 2010

Volume

15

Issue

5

Start / End Page

512 / 446

Related Subject Headings

  • Tritium
  • Time Factors
  • Synaptic Transmission
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin
  • Receptor, Serotonin, 5-HT1A
  • Pyridines
  • Psychiatry
  • Protein Binding
  • Positron-Emission Tomography