Cognitive impact of genetic variation of the serotonin transporter in primates is associated with differences in brain morphology rather than serotonin neurotransmission
Open Access
- 1 September 2009
- journal article
- research article
- Published by Springer Science and Business Media LLC in Molecular Psychiatry
- Vol. 15 (5), 512-522
- https://doi.org/10.1038/mp.2009.90
Abstract
A powerful convergence of genetics, neuroimaging and epidemiological research has identified biological pathways mediating individual differences in complex behavioral processes and related risk for disease. Orthologous genetic variation in non-human primates represents a unique opportunity to characterize the detailed molecular and cellular mechanisms which 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 Short allele broadly impacts cognitive choice behavior and brain morphology without observably affecting 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 non-human primate models in advancing our understanding of human genetic variation impacting behavior and neuropsychiatric disease liability.This publication has 59 references indexed in Scilit:
- Serotonin transporter binding and genotype in the nonhuman primate brain using [C-11]DASB PETNeuroImage, 2009
- Serotonin Transporter Genotype Modulates Social Reward and Punishment in Rhesus MacaquesPLOS ONE, 2009
- Serotonin Transporter (5-HTTLPR) Genotype and Amygdala Activation: A Meta-AnalysisBiological Psychiatry, 2008
- The serotonin transporter genotype is associated with intermediate brain phenotypes that depend on the context of eliciting stressorMolecular Psychiatry, 2008
- The neural correlates of subjective value during intertemporal choiceNature Neuroscience, 2007
- The Effect of Acute Tryptophan Depletion on the Neural Correlates of Emotional Processing in Healthy VolunteersNeuropsychopharmacology, 2007
- Genetic modulation of cognitive flexibility and socioemotional behavior in rhesus monkeysProceedings of the National Academy of Sciences of the United States of America, 2007
- Temporal Discounting Predicts Risk Sensitivity in Rhesus MacaquesCurrent Biology, 2007
- The effect of polymorphism at the serotonin transporter gene on decision-making, memory and executive function in ecstasy users and controlsPsychopharmacology, 2006
- The effects of acute tryptophan depletion and serotonin transporter polymorphism on emotional processing in memory and attentionInternational Journal of Neuropsychopharmacology, 2006