title: Serotonin transporter genotype affects serotonin 5-HT1A binding in primates.
abstract: Disruption of the serotonin system has been implicated in anxiety and depression and a related genetic variation has been identified that may predispose individuals for these illnesses. The relationship of a functional variation of the serotonin transporter promoter gene (5-HTTLPR) on serotonin transporter binding using in vivo imaging techniques have yielded inconsistent findings when comparing variants for short (s) and long (l) alleles. However, a significant 5-HTTLPR effect on receptor binding at the 5-HT(1A) receptor site has been reported in humans, suggesting the 5-HTTLPR polymorphism may play a role in serotonin (5-HT) function. Rhesus monkeys possess a 5-HTTLPR length polymorphism similar to humans and serve as an excellent model for studying the effects of this orthologous genetic variation on behaviors and neurochemical functions related to the 5-HT system. In this study, PET imaging of [(18)F]mefway was performed on 58 rhesus monkeys (33 l/l, 25 s-carriers) to examine the relation between 5-HT(1A) receptor-specific binding and 5-HTTLPR genotypes. Significantly lower 5-HT(1A) binding was found in s-carrier subjects throughout both cortical brain regions and the raphe nuclei. These results demonstrate that the underlying 5-HT neurochemical system is influenced by this functional polymorphism and illustrate the strong potential for extending the nonhuman primate model into investigating the role of this genetic variant on behavior and gene-environment interactions.
authors: Department of Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin 53705, USA. bchristian@wisc.edu
authors: Bradley T
authors: BT
authors: Christian
authors: Dustin W
authors: DW
authors: Wooten
authors: Ansel T
authors: AT
authors: Hillmer
authors: Dana L
authors: DL
authors: Tudorascu
authors: Alexander K
authors: AK
authors: Converse
authors: Colleen F
authors: CF
authors: Moore
authors: Elizabeth O
authors: EO
authors: Ahlers
authors: Todd E
authors: TE
authors: Barnhart
authors: Ned H
authors: NH
authors: Kalin
authors: Christina S
authors: CS
authors: Barr
authors: Mary L
authors: ML
authors: Schneider
mesh_terms: D000818:Animals; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D008253:Macaca mulatta; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics*; D011485:Protein Binding / Q000235:genetics; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics* / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D044282:Receptor, Serotonin, 5-HT1A
references: Mol Psychiatry. 2008 Nov;13(11):1021-7
references: 18414408
references: Mol Psychiatry. 2002;7(1):118-22
references: 11803458
references: Arch Gen Psychiatry. 2004 Nov;61(11):1146-52
references: 15520362
references: Biol Psychiatry. 2004 Apr 1;55(7):733-8
references: 15039002
references: Nat Neurosci. 2007 Sep;10(9):1103-9
references: 17726476
references: Child Dev. 1997 Oct;68(5):747-759
references: 29106730
references: J Nucl Med. 2006 Oct;47(10):1697-706
references: 17015907
references: Synapse. 2003 Jun 15;48(4):184-8
references: 12687637
references: Biol Psychiatry. 2007 Aug 15;62(4):327-31
references: 17210141
references: Neuroimage. 2009 Mar 1;45(1):52-9
references: 19059346
references: J Cereb Blood Flow Metab. 2007 Sep;27(9):1533-9
references: 17519979
references: J Neurosci. 2005 Mar 9;25(10):2586-90
references: 15758168
references: Am J Psychiatry. 2004 Mar;161(3):525-31
references: 14992979
references: Child Dev. 1999 Mar-Apr;70(2):263-74
references: 10218255
references: Science. 1996 Nov 29;274(5292):1527-31
references: 8929413
references: Neuroimage. 2009 Oct 1;47(4):1230-6
references: 19505582
references: Synapse. 2011 Jul;65(7):592-600
references: 21484878
references: Mol Psychiatry. 1996 Dec;1(6):453-60
references: 9154246
references: Alcohol Clin Exp Res. 2003 May;27(5):812-7
references: 12766626
references: Int J Neuropsychopharmacol. 2009 Jul;12(6):783-92
references: 19126263
references: Am J Psychiatry. 2000 Oct;157(10):1700-3
references: 11007732
references: Phys Med Biol. 2001 Jul;46(7):1845-62
references: 11474929
references: Ann N Y Acad Sci. 2006 Dec;1094:52-62
references: 17347341
references: Am J Psychiatry. 2006 Jan;163(1):48-51
references: 16390888
references: Biol Psychiatry. 2008 Feb 1;63(3):317-24
references: 17884019
references: J Cereb Blood Flow Metab. 2003 Sep;23(9):1096-112
references: 12973026
references: Mol Psychiatry. 2002;7(10):1058-63
references: 12476320
references: Biol Psychiatry. 2000 Apr 1;47(7):643-9
references: 10745057
references: Proc Natl Acad Sci U S A. 2007 Aug 28;104(35):14128-33
references: 17715054
references: Mol Psychiatry. 2010 May;15(5):512-22, 446
references: 19721434
references: J Neural Transm (Vienna). 2007;114(5):635-9
references: 17225932