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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • 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 Date

  • May 2010

Published In

Volume / Issue

  • 15 / 5

Start / End Page

  • 512 - 446

PubMed ID

  • 19721434

Pubmed Central ID

  • PMC2861147

Electronic International Standard Serial Number (EISSN)

  • 1476-5578

International Standard Serial Number (ISSN)

  • 1359-4184

Digital Object Identifier (DOI)

  • 10.1038/mp.2009.90


  • eng