期刊
MOLECULAR PSYCHIATRY
卷 15, 期 5, 页码 512-522出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/mp.2009.90
关键词
5-HTTLPR; serotonin transporter; polymorphism; cognition; development; rhesus macaque
资金
- NARSAD
- NIH/NIAAA [014646]
- Office of Research and Development Medical Research Service, Department of Veterans Affairs
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. Molecular Psychiatry (2010) 15, 512-522; doi:10.1038/mp.2009.90; published online 1 September 2009
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