1. Cognitive impact of genetic variation of the serotonin transporter in primates is associated with differences in brain morphology rather than serotonin neurotransmission.
- Author
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Jedema HP, Gianaros PJ, Greer PJ, Kerr DD, Liu S, Higley JD, Suomi SJ, Olsen AS, Porter JN, Lopresti BJ, Hariri AR, and Bradberry CW
- Subjects
- Animals, Avoidance Learning physiology, Behavior, Animal physiology, Benzylamines metabolism, Brain diagnostic imaging, Brain drug effects, Brain Mapping, Carbon Isotopes metabolism, Genotype, Macaca mulatta, Magnetic Resonance Imaging methods, Male, Neuropsychological Tests, Piperazines metabolism, Positron-Emission Tomography methods, Protein Binding drug effects, Protein Binding genetics, Pyridines metabolism, Receptor, Serotonin, 5-HT1A genetics, Serotonin genetics, Time Factors, Tritium metabolism, Choice Behavior physiology, Cognition physiology, Polymorphism, Genetic genetics, Serotonin metabolism, Serotonin Plasma Membrane Transport Proteins genetics, Synaptic Transmission genetics
- 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-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.
- Published
- 2010
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