Polymorphisms in the 3′ UTR of the serotonin transporter are associated with cognitive flexibility in rhesus macaques

American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics

Volumn 150, Issue 4, 2009, Pages 467-475

  Vallender, Eric J ^a   Lynch, Laurie ^a   Novak, Melinda A ^a   Miller, Gregory M ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

Author keywords

Gene expression; Genotype phenotype association; Neurogenetics; Psychiatric genetics; Reversal learning

Indexed keywords

SEROTONIN TRANSPORTER;

3' UNTRANSLATED REGION; 5HTTLPR GENE; ADOLESCENT; ANIMAL EXPERIMENT; ARTICLE; COGNITION; CONTROLLED STUDY; GENE EXPRESSION; GENE LOCUS; GENETIC LINKAGE; GENETIC POLYMORPHISM; GENETIC VARIABILITY; HAPLOTYPE; LEARNING; MALE; NONHUMAN; PRIORITY JOURNAL; RHESUS MONKEY; SEROTONINERGIC SYSTEM; SOCIAL INTERACTION; ANIMAL; ANIMAL BEHAVIOR; GENE FREQUENCY; GENETICS; MACACA; PHYSIOLOGY; PROMOTER REGION; SINGLE NUCLEOTIDE POLYMORPHISM;

MACACA; MACACA MULATTA;

3' UNTRANSLATED REGIONS; ANIMALS; BEHAVIOR, ANIMAL; COGNITION; GENE FREQUENCY; HAPLOTYPES; MACACA MULATTA; MALE; POLYMORPHISM, SINGLE NUCLEOTIDE; PROMOTER REGIONS, GENETIC; SEROTONIN PLASMA MEMBRANE TRANSPORT PROTEINS;

EID: 66649134175     PISSN: 15524841     EISSN: 1552485X     Source Type: Journal    
DOI: 10.1002/ajmg.b.30835     Document Type: Article

References (75)

1. Bechara A, Dolan S, Denburg N, Hindes A, Anderson SW, Nathan PE. 2001. Decision-making deficits, linked to a dysfunctional ventromedial prefrontal cortex, revealed in alcohol and stimulant abusers. Neuropsychologia 39(4):376-389. (Pubitemid 32065803)
2. Bennett AJ, Lesch KP, Heils A, Long JC, Lorenz JG, Shoaf SE, Champoux M, Suomi SJ, Linnoila MV, Higley JD. 2002. Early experience and serotonin transporter gene variation interact to influence primate CNS function. Mol Psychiatry 7(1):118-122. (Pubitemid 34087891)
3. Brown SM, Peet E, Manuck SB, Williamson DE, Dahl RE, Ferrell RE, Hariri AR. 2005. A regulatory variant of the human tryptophan hydroxylase-2 gene biases amygdala reactivity. Mol Psychiatry 10(9):884-888, 805. (Pubitemid 43080111)
4. Charney DS. 1998. Monoamine dysfunction and the pathophysiology and treatment of depression. J Clin Psychiatry 59(Suppl14): 11-114. (Pubitemid 28462383)
5. Chen GL, Novak MA, Hakim S, Xie Z, Miller GM. 2006. Tryptophan hydroxylase-2 gene polymorphisms in rhesus monkeys: Association with hypothalamic-pituitary-adrenal axis function and in vitro gene expression. Mol Psychiatry 11(10):914-928. (Pubitemid 44470214)
6. Chen GL, Vallender EJ, Miller GM. 2008. Functional characterization of the human TPH2 50 regulatory region: Untranslated region and polymorphisms modulate gene expression in vitro. Hum Genet 122(6):645-657.
7. Clark L, Cools R, Robbins TW. 2004. The neuropsychology of ventral prefrontal cortex: Decision-making and reversal learning. Brain Cogn 55(1):41-53. (Pubitemid 38591429)
8. Clarke HF, Dalley JW, Crofts HS, Robbins TW, Roberts AC. 2004. Cognitive inflexibility after prefrontal serotonin depletion. Science 304(5672):878-880. (Pubitemid 38620188)
9. Clarke HF, Walker SC, Crofts HS, Dalley JW, Robbins TW, Roberts AC. 2005. Prefrontal serotonin depletion affects reversal learning but not attentional set shifting. J Neurosci 25(2):532-538. (Pubitemid 40105626)
10. Clarke HF, Walker SC, Dalley JW, Robbins TW, Roberts AC. 2007. Cognitive inflexibility after prefrontal serotonin depletion is behaviorally and neurochemically specific. Cereb Cortex 17(1):18-27. (Pubitemid 44973891)
11. Cools R, Roberts AC, Robbins TW. 2008. Serotoninergic regulation of emotional and behavioural control processes. Trends Cogn Sci 12(1):31-40. (Pubitemid 50012215)
12. Devor EJ, Magee HJ, Dill-Devor RM, Gabel J, Black DW. 1999. Serotonin transporter gene (5-HTT) polymorphisms and compulsive buying. Am J Med Genet 88(2):123-125. (Pubitemid 29156447)
13. Di Bella DD, Catalano M, Cavallini MC, Riboldi C, Bellodi L. 2000. Serotonin transporter linked polymorphic region in anorexia nervosa and bulimia nervosa. Mol Psychiatry 5(3):233-234. (Pubitemid 30438394)
14. Dias R, Robbins TW, Roberts AC. 1996. Primate analogue of the Wisconsin Card Sorting Test: Effects of excitotoxic lesions of the prefrontal cortex in the marmoset. Behav Neurosci 110(5):872-886. (Pubitemid 26365787)
15. Dom G, Sabbe B, Hulstijn W, van den Brink W. 2005. Substance use disorders and the orbitofrontal cortex: Systematic review of behavioural decision-making and neuroimaging studies. Br J Psychiatry 187:209-220. (Pubitemid 41306101)
16. Evers EA, Cools R, Clark L, van der Veen FM, Jolles J, Sahakian BJ, Robbins TW. 2005. Serotonergic modulation of prefrontal cortex during negative feedback in probabilistic reversal learning. Neuropsychopharmacology 30(6):1138-1147. (Pubitemid 40720972)
17. Fairbanks LA, Fontenot MB, Phillips-Conroy JE, Jolly CJ, Kaplan JR, Mann JJ. 1999. CSF monoamines, age and impulsivity in wild grivet monkeys (Cercopithecus aethiops aethiops). Brain Behav Evol 53(5-6):305-312. (Pubitemid 29406296)
18. Fallon S, Shearman E, Sershen H, Lajtha A. 2007. Food reward-induced neurotransmitter changes in cognitive brain regions. Neurochem Res 32(10):1772-1782. (Pubitemid 47428853)
19. Fan JB, Sklar P. 2005. Meta-analysis reveals association between serotonin transporter gene STin2 VNTR polymorphism and schizophrenia. Mol Psychiatry 10(10):928-938, 891. (Pubitemid 41486480)
20. Fellows LK, Farah MJ. 2003. Ventromedial frontal cortex mediates affective shifting in humans: Evidence from a reversal learning paradigm. Brain 126(Pt8): 1830-1837. (Pubitemid 36917342)
21. Filip M, Frankowska M, Zaniewska M, Golda A, Przegalinski E. 2005. The serotonergic system and its role in cocaine addiction. Pharmacol Rep 57(6):685-700.
22. Fumeron F, Betoulle D, Aubert R, Herbeth B, Siest G, Rigaud D. 2001. Association of a functional 5-HT transporter gene polymorphism with anorexia nervosa and food intake. Mol Psychiatry 6(1):9-10. (Pubitemid 32096059)
23. Garavan H, Stout JC. 2005. Neurocognitive insights into substance abuse. Trends Cogn Sci 9(4):195-201. (Pubitemid 40543255)
24. Glatt CE, Reus VI. 2003. Pharmacogenetics of monoamine transporters. Pharmacogenomics 4(5):583-596. (Pubitemid 37120946)
25. Goudriaan AE, Oosterlaan J, de Beurs E, Van den Brink W. 2004. Pathological gambling: A comprehensive review of biobehavioral findings. Neurosci Biobehav Rev 28(2):123-141. (Pubitemid 38692361)
26. Graeff FG, Brandao ML, Audi EA, Schutz MT. 1986. Modulation of the brain aversive system by GABAergic and serotonergic mechanisms. Behav Brain Res 22(2):173-180. (Pubitemid 17182276)
27. Grant S, Contoreggi C, London ED. 2000. Drug abusers show impaired performance in a laboratory test of decision making. Neuropsychologia 38(8):1180-1187.
28. Heils A, Teufel A, Petri S, Seemann M, Bengel D, Balling U, Riederer P, Lesch KP. 1995. Functional promoter and polyadenylation site mapping of the human serotonin (5-HT) transporter gene. J Neural Transm Gen Sect 102(3):247-254. (Pubitemid 26010732)
29. Heils A, Teufel A, Petri S, Stober G, Riederer P, Bengel D, Lesch KP. 1996. Allelic variation of human serotonin transporter gene expression. J Neurochem 66(6):2621-2624. (Pubitemid 26159101)
30. Higley JD, Linnoila M. 1997. Low central nervous system serotonergic activity is traitlike and correlates with impulsive behavior. A nonhuman primate model investigating genetic and environmental influences on neurotransmission. Ann NY Acad Sci 836:39-56.
31. Izquierdo A, Suda RK, Murray EA. 2004. Bilateral orbital prefrontal cortex lesions in rhesus monkeys disrupt choices guided by both reward value and reward contingency. J Neurosci 24(34):7540-7548. (Pubitemid 39166745)
32. Izquierdo A, Newman TK, Higley JD, Murray EA. 2007. Genetic modulation of cognitive flexibility and socioemotional behavior in rhesus monkeys. Proc Natl Acad Sci USA 104(35):14128-14133. (Pubitemid 350003346)
33. Jentsch JD, Olausson P, De La Garza R II, Taylor JR. 2002. Impairments of reversal learning and response perseveration after repeated, intermittent cocaine administrations to monkeys. Neuropsychopharmacology 26(2):183-190. (Pubitemid 34093081)
34. Johnson BA. 2004. Role of the serotonergic system in the neurobiology of alcoholism: Implications for treatment. CNS Drugs 18(15):1105-1118. (Pubitemid 40007493)
35. Jollant F, Bellivier F, Leboyer M, Astruc B, Torres S, Verdier R, Castelnau D, Malafosse A, Courtet P. 2005. Impaired decision making in suicide attempters. Am J Psychiatry 162(2):304-310. (Pubitemid 40216211)
36. Jollant F, Buresi C, Guillaume S, Jaussent I, Bellivier F, Leboyer M, Castelnau D, Malafosse A, Courtet P. 2007. The influence of four serotonin-related genes on decision-making in suicide attempters. Am J Med Genet Part B 144B(5):615-624. (Pubitemid 47077145)
37. Jones B, Mishkin M. 1972. Limbic lesions and the problem of stimulus- reinforcement associations. Exp Neurol 36(2):362-377.
38. Koob GF. 2000. Neurobiology of addiction. Toward the development of new therapies. Ann NY Acad Sci 909:170-185.
39. Lajtha A. 2008. Interrelated mechanisms in reward and learning. Neurochem Int 52(1-2):73-79. (Pubitemid 350235719)
40. Lappalainen J, Zhang L, Dean M, Oz M, Ozaki N, Yu DH, Virkkunen M, Weight F, Linnoila M, Goldman D. 1995. Identification, expression, and pharmacology of a Cys23-Ser23 substitution in the human 5-HT2c receptor gene (HTR2C). Genomics 27(2):274-279.
41. Lee JH, Kim HT, Hyun DS. 2003. Possible association between serotonin transporter promoter region polymorphism and impulsivity in Koreans. Psychiatry Res 118(1):19-24. (Pubitemid 36577556)
42. Lee D, Rushworth MF, Walton ME, Watanabe M, Sakagami M. 2007. Functional specialization of the primate frontal cortex during decision making. J Neurosci 27(31):8170-8173. (Pubitemid 47219599)
43. Leonardo ED, Hen R. 2006. Genetics of affective and anxiety disorders. Annu Rev Psychol 57:117-137.
44. Lesch KP, Bengel D, Heils A, Sabol SZ, Greenberg BD, Petri S, Benjamin J, Muller CR, Hamer DH, Murphy DL. 1996. Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 274(5292):1527-1531. (Pubitemid 26403928)
45. Lesch KP, Meyer J, Glatz K, Flugge G, Hinney A, Hebebrand J, Klauck SM, Poustka A, Poustka F, Bengel D, et al. 1997. The 5-HT transporter gene-linked polymorphic region (5-HTTLPR) in evolutionary perspective: Alternative biallelic variation in rhesus monkeys. Rapid communication. J Neural Transm 104(11-12):1259-1266. (Pubitemid 28031819)
46. Lin Z, Madras BK. 2006. Human genetics and pharmacology of neurotransmitter transporters. Handb Exp Pharmacol 175:327-371.
47. Liu YP, Wilkinson LS, Robbins TW. 2004. Effects of acute and chronic buspirone on impulsive choice and efflux of 5-HT and dopamine in hippocampus, nucleus accumbens and prefrontal cortex. Psychopharmacology (Berl) 173(1-2):175-185. (Pubitemid 38591163)
48. Liu S, Heitz RP, Sampson AR, Zhang W, Bradberry CW. 2007. Evidence of temporal cortical dysfunction in rhesus monkeys following chronic cocaine self-administration. Cereb Cortex [Epub ahead of print].
49. Matsushita S, Nakamura T, Nishiguchi N, Higuchi S. 2002. Association of serotonin transporter regulatory region polymorphism and abnormal eating behaviors. Mol Psychiatry 7(6):538-540.
50. Muller CP, Carey RJ, Huston JP, De Souza Silva MA. 2007. Serotonin and psychostimulant addiction: Focus on 5-HT1A-receptors. Prog Neurobiol 81(3):133-178. (Pubitemid 46282275)
51. Murray EA, O'Doherty JP, Schoenbaum G. 2007. What we know and do not know about the functions of the orbitofrontal cortex after 20 years of cross-species studies. J Neurosci 27(31):8166-8169. (Pubitemid 47219598)
52. Newman TK, Syagailo YV, Barr CS, Wendland JR, Champoux M, Graessle M, Suomi SJ, Higley JD, Lesch KP. 2005. Monoamine oxidase A gene promoter variation and rearing experience influences aggressive behavior in rhesus monkeys. Biol Psychiatry 57(2):167-172. (Pubitemid 40094717)
53. Nordin C, Sjodin I. 2006. CSF monoamine patterns in pathological gamblers and healthy controls. J Psychiatr Res 40(5):454-459. (Pubitemid 43816584)
54. Owens MJ, Nemeroff CB. 1994. Role of serotonin in the pathophysiology of depression: Focus on the serotonin transporter. Clin Chem 40(2):288-295. (Pubitemid 24072594)
55. Pardo CA, Eberhart CG. 2007. The neurobiology of autism. Brain Pathol 17(4):434-447. (Pubitemid 47537607)
56. Perez de Castro I, Ibanez A, Saiz-Ruiz J, Fernandez-Piqueras J. 1999. Genetic contribution to pathological gambling: Possible association between a functional DNA polymorphism at the serotonin transporter gene (5-HTT) and affected men. Pharmacogenetics 9(3):397-400. (Pubitemid 29376385)
57. Perez de Castro I, Ibanez A, Saiz-Ruiz J, Fernandez-Piqueras J. 2002. Concurrent positive association between pathological gambling and functional DNA polymorphisms at the MAO-A and the 5-HT transporter genes. Mol Psychiatry 7(9):927-928. (Pubitemid 35333044)
58. Prasad S, Semwal P, Deshpande S, Bhatia T, Nimgaonkar VL, Thelma BK. 2002. Molecular genetics of schizophrenia: Past, present and future. J Biosci 27(1 Suppl 1):35-52. (Pubitemid 34285618)
59. Rahman S, Sahakian BJ, Cardinal RN, Rogers RD, Robbins TW. 2001. Decision making and neuropsychiatry. Trends Cogn Sci 5(6):271-277. (Pubitemid 32493004)
60. Rogers RD, Robbins TW. 2001. Investigating the neurocognitive deficits associated with chronic drug misuse. Curr Opin Neurobiol 11(2):250-257. (Pubitemid 32289414)
61. Rogers RD, Blackshaw AJ, Middleton HC, Matthews K, Hawtin K, Crowley C, Hopwood A, Wallace C, Deakin JF, Sahakian BJ, et al. 1999. Tryptophan depletion impairs stimulus-reward learning while methylphenidate disrupts attentional control in healthy young adults: Implications for the monoaminergic basis of impulsive behaviour. Psychopharmacology (Berl) 146(4):482-491. (Pubitemid 29513289)
62. Rogers RD, Tunbridge EM, Bhagwagar Z, Drevets WC, Sahakian BJ, Carter CS. 2003. Tryptophan depletion alters the decision-making of healthy volunteers through altered processing of reward cues. Neuropsychopharmacology 28(1):153-162.
63. Sabol SZ, Hu S, Hamer D. 1998. A functional polymorphism in the monoamine oxidase A gene promoter. Hum Genet 103(3):273-279. (Pubitemid 28470076)
64. Sakado K, Sakado M, Muratake T, Mundt C, Someya T. 2003. A psychometrically derived impulsive trait related to a polymorphism in the serotonin transporter gene-linked polymorphic region (5-HTTLPR) in a Japanese nonclinical population: Assessment by the Barratt impulsiveness scale (BIS). Am J Med Genet Part B 121B(1):71-75. (Pubitemid 37064033)
65. Schinka JA, Busch RM, Robichaux-Keene N. 2004. A meta-analysis of the association between the serotonin transporter gene polymorphism (5-HTTLPR) and trait anxiety. Mol Psychiatry 9(2):197-202. (Pubitemid 38299534)
66. Sen S, Burmeister M, Ghosh D. 2004. Meta-analysis of the association between a serotonin transporter promoter polymorphism (5-HTTLPR) and anxiety-related personality traits. Am J Med Genet Part B 127B(1):85-89. (Pubitemid 38542320)
67. Soubrie P. 1986. Reconciling the role of central serotonin neurons in human and animal behavior. Behav Brain Sci 9(2):319-335.
68. Trefilov A, Krawczak M, Berard J, Schmidtke J. 1999. DNA sequence polymorphisms in genes involved in the regulation of dopamine and serotonin metabolism in rhesus macaques. Electrophoresis 20(8):1771-1777. (Pubitemid 29320473)
69. Trefilov A, Berard J, Krawczak M, Schmidtke J. 2000. Natal dispersal in rhesus macaques is related to serotonin transporter gene promoter variation. Behav Genet 30(4):295-301. (Pubitemid 32106119)
70. Vallender EJ, Priddy CM, Hakim S, Yang H, Chen GL, Miller GM. 2008. Functional variation in the 30 UTRof the serotonin transporter in human and rhesus macaque. Genes Brain Behav [Epub ahead of print].
71. Verrico CD, Lynch L, Fahey MA, Fryer AK, Miller GM, Madras BK. 2008. MDMA-induced impairment in primates: Antagonism by a selective norepinephrine or serotonin, but not by a dopamine/norepinephrine transport inhibitor. J Psychopharmacol 22(2):187-202.
72. Winstanley CA. 2007. The orbitofrontal cortex, impulsivity, and addiction: Probing orbitofrontal dysfunction at the neural, neurochemical, and molecular level. Ann NY Acad Sci 1121:639-655.
73. Wu S, Comings DE. 1999. A common C-1018G polymorphism in the human 5-HT1A receptor gene. Psychiatr Genet 9(2):105-106.
74. Yucel M, Lubman DI, Solowij N, Brewer WJ. 2007. Understanding drug addiction: A neuropsychological perspective. Aust N Z J Psychiatry 41(12):957-968. (Pubitemid 350120825)
75. Zhang X, Gainetdinov RR, Beaulieu JM, Sotnikova TD, Burch LH, Williams RB, Schwartz DA, Krishnan KR, Caron MG. 2005. Loss-offunction mutation in tryptophan hydroxylase-2 identified in unipolar major depression. Neuron 45(1):11-16. (Pubitemid 40075345)