The 5-HTTLPR polymorphism is associated with altered hemodynamic responses during appetitive conditioning

Human Brain Mapping

Volumn 34, Issue 10, 2013, Pages 2549-2560

  Klucken, Tim ^a   Wehrum, Sina ^a   Schweckendiek, Jan ^a   Merz, Christian Josef ^a   Hennig, Juergen ^a   Vaitl, Dieter ^a   Stark, Rudolf ^a  

^a JUSTUS LIEBIG UNIVERSITY   (Germany)

Author keywords

5 HTTLPR; Amygdala; Classical conditioning; FMRI; Imaging genetics; Positive emotion

Indexed keywords

SEROTONIN TRANSPORTER;

ADULT; AMYGDALOID NUCLEUS; APPETITE; ARTICLE; BRAIN DEPTH STIMULATION; CEREBELLUM; CONDITIONING; CORPUS STRIATUM; ECHO PLANAR IMAGING; ELECTRODERMAL RESPONSE; FEMALE; FOLLOW UP; FUNCTIONAL MAGNETIC RESONANCE IMAGING; GENETIC ASSOCIATION; GENETIC POLYMORPHISM; GENOTYPE; HEMODYNAMICS; HUMAN; INSULA; MAJOR CLINICAL STUDY; MALE; MIDDLE FRONTAL GYRUS; ORBITAL CORTEX; POSTERIOR CINGULATE; PRIORITY JOURNAL; SUPPLEMENTARY MOTOR AREA; THALAMUS;

5-HTTLPR; AMYGDALA; CLASSICAL CONDITIONING; FMRI; IMAGING GENETICS; POSITIVE EMOTION;

ADULT; ALLELES; AMYGDALA; APPETITIVE BEHAVIOR; BRAIN MAPPING; CEREBRAL CORTEX; CEREBROVASCULAR CIRCULATION; CONDITIONING, OPERANT; CORPUS STRIATUM; ECHO-PLANAR IMAGING; EROTICA; FEMALE; FRONTAL LOBE; GALVANIC SKIN RESPONSE; GENOTYPE; GYRUS CINGULI; HEMODYNAMICS; HUMANS; INDEL MUTATION; MALE; SEROTONIN PLASMA MEMBRANE TRANSPORT PROTEINS; SEXUAL BEHAVIOR; THALAMUS; YOUNG ADULT;

EID: 84883789059     PISSN: 10659471     EISSN: 10970193     Source Type: Journal    
DOI: 10.1002/hbm.22085     Document Type: Article

References (95)

1. Abler B, Seeringer A, Hartmann A, Grön G, Metzger C, Walter M, Stingl J (2011): Neural correlates of antidepressant-related sexual dysfunction: A placebo-controlled FMRI study on healthy males under subchronic paroxetine and bupropion. Neuropsychopharmacology 36:1837-1847.
2. Ahrold TK, Meston CM (2009): Effects of SNS activation on SSRI-induced sexual side effects differ by SSRI. J Sex Marital Ther 35:311-319.
3. Alexander N, Kuepper Y, Schmitz A, Osinsky R, Kozyra E, Hennig J (2009): Gene-environment interactions predict cortisol responses after acute stress: Implications for the etiology of depression. Psychoneuroendocrinology 34:1294-1303.
4. Barcikowski RS, Robey RR (1984): Decisions in single group repeated measures analysis: Statistical tests and three computer packages. Am Statist 38:148-150.
5. Beevers CG, Pacheco J, Clasen P, McGeary JE, Schnyer D (2010): Prefrontal morphology, 5-HTTLPR polymorphism and biased attention for emotional stimuli. Genes Brain Behav 9:224-233.
6. Beevers CG, Marti CN, Lee H, Stote DL, Ferrell RE, Hariri AR, Telch MJ (2011): Associations between serotonin transporter gene promoter region (5-HTTLPR) polymorphism and gaze bias for emotional information. J Abnorm Psychol 120:187-197.
7. Belsky J, Jonassaint C, Pluess M, Stanton M, Brummett B, Williams R (2009): Vulnerability genes or plasticity genes?Mol Psychiatry 14:746-754.
8. Boik RJ (1981): A priori tests in repeated measures designs: Effects of nonsphericity. Psychometrika 46:241-255.
9. Bonardi C, Bartle C, Bowles K, Pulford F de, Jennings DJ (2010): Some appetitive procedures for examining associative learning in the mouse: Implications for psychopathology. Behav Brain Res 211:240-247.
10. Both S, Laan E, Spiering M, Nilsson T, Oomens S, Everaerd W (2008a): Appetitive and aversive classical conditioning of female sexual response. J Sex Med 5:1386-1401.
11. Both S, Spiering M, Laan E, Belcome S, van den Heuvel B, Everaerd W (2008b): Unconscious classical conditioning of sexual arousal: Evidence for the conditioning of female genital arousal to subliminally presented sexual stimuli. J Sex Med 5:100-109.
12. Boureau Y, Dayan P (2011): Opponency revisited: Competition and cooperation between dopamine and serotonin. Biol Psychiatry 36:74-97.
13. Brown SM, Hariri AR (2006): Neuroimaging studies of serotonin gene polymorphisms: Exploring the interplay of genes, brain, and behavior. Cogn Affect Behav Neurosci 6:44-52.
14. Büchel C, Dolan RJ (2000): Classical fear conditioning in functional neuroimaging. Curr Opin Neurobiol 10:219-223.
15. Burke KA, Franz TM, Miller DN, Schoenbaum G (2008): The role of the orbitofrontal cortex in the pursuit of happiness and more specific rewards. Nature 454:340-344.
16. Cahill L (2006): Why sex matters for neuroscience. Nat Rev Neurosci 7:477-484.
17. Canli T, Lesch K (2007): Long story short: The serotonin transporter in emotion regulation and social cognition. Nat Neurosci 10:1103-1109.
18. Caspi A, Hariri AR, Holmes A, Uher R, Moffitt TE (2010): Genetic sensitivity to the environment: The case of the serotonin transporter gene and its implications for studying complex diseases and traits. Am J Psychiatry 167:509-527.
19. Chauvet C, Lardeux V, Jaber M, Solinas M (2011): Brain regions associated with the reversal of cocaine conditioned place preference by environmental enrichment. Neuroscience 184:88-96.
20. Cox SML, Andrade A, Johnsrude IS (2005): Learning to like: A role for human orbitofrontal cortex in conditioned reward. J Neurosci 25:2733-2740.
21. Craig ADB (2009): How do you feel-now? The anterior insula and human awareness. Nat Rev Neurosci 10:59-70.
22. Craig ADB (2011): Significance of the insula for the evolution of human awareness of feelings from the body. Ann NY Acad Sci 1225:72-82.
23. Crişan LG, Pana S, Vulturar R, Heilman RM, Szekely R, Druga B, Dragoş N, Miu AC (2009): Genetic contributions of the serotonin transporter to social learning of fear and economic decision making. Soc Cogn Affect Neurosci 4:399-408.
24. Critchley HD (2004): The human cortex responds to an interoceptive challenge. Proc Natl Acad Sci USA 101:6333-6334.
25. Day JJ, Carelli RM (2007): The nucleus accumbens and Pavlovian reward learning. Neuroscientist 13:148-159.
26. Delgado MR, Olsson A, Phelps EA (2006): Extending animal models of fear conditioning to humans. Biol Psychol 73:39-48.
27. Etkin A, Egner T, Kalisch R (2011): Emotional processing in anterior cingulate and medial prefrontal cortex. Trends Cogn Sci 15:85-93.
28. Feinn R, Nellissery M, Kranzler HR (2005): Meta-analysis of the association of a functional serotonin transporter promoter polymorphism with alcohol dependence. Am J Med Genet B 133:79-84.
29. Fox PT, Lancaster JL (1994): Neuroscience on the net. Science 266:994-996.
30. Franklin S, Hall G (2011): Analysis of us-preexposure effects in appetitive conditioning. J Exp Psychol Anim Behav Process 37:495-500.
31. Friston KJ, Ashburner JT, Kiebel S, Nichols T, Penny WD, editors (2007):Statistical Parametric Mapping: The Analysis of Functional Brain Images.Amsterdam:Elsevier Acad. Press.32 p.
32. Furmark T, Tillfors M, Garpenstrand H, Marteinsdottir I, Långström B, Oreland L, Fredrikson M (2004): Serotonin transporter polymorphism related to amygdala excitability and symptom severity in patients with social phobia. Neurosci Lett 362:189-192.
33. Garpenstrand H, Annas P, Ekblom J, Oreland L, Fredrikson M (2001): Human fear conditioning is related to dopaminergic and serotonergic biological markers. Behav Neurosci 115:358-364.
34. Gillihan SJ, Rao H, Wang J, Detre JA, Breland J, Sankoorikal GMV, Brodkin ES, Farah MJ (2010): Serotonin transporter genotype modulates amygdala activity during mood regulation. Soc Cogn Affect Neurosci 5:1-10.
35. Haber SN, Knutson B (2010): The reward circuit: Linking primate anatomy and human imaging. Neuropsychopharmacology 35:4-26.
36. Hamm AO, Weike AI (2005): The neuropsychology of fear learning and fear regulation. Int J Psychophysiol 57:5-14.
37. Hariri AR, Drabant EM, Munoz KE, Kolachana BS, Mattay VS, Egan MF, Weinberger DR (2005): A susceptibility gene for affective disorders and the response of the human amygdala. Arch Gen Psychiatry 62:146-152.
38. Hayes DJ, Greenshaw AJ (2011): 5-HT receptors and reward-related behaviour: A review. Neurosci Biobehav Rev 35:1419-1449.
39. Hettema JM, Annas P, Neale MC, Kendler KS, Fredrikson M (2003): A twin study of the genetics of fear conditioning. Arch Gen Psychiatry 60:702-708.
40. Hoffmann H, Janssen E, Turner SL (2004): Classical conditioning of sexual arousal in women and men: Effects of varying awareness and biological relevance of the conditioned stimulus. Arch Sexual Behav 33:43-53.
41. Homberg JR (2012): Serotonin and decision making processes. Neurosci Biobehav Rev 36:218-236.
42. Homberg JR, Lesch K (2011): Looking on the bright side of serotonin transporter gene variation. Biol Psychiatry 69:513-519.
43. Homberg JR, de Boer SF, Raas{circled division slash} HS, Olivier JDA, Verheul M, Ronken E, Cools AR, Ellenbroek BA, Schoffelmeer ANM, Vanderschuren LJMJ, de Vries TJ, Cuppen E (2008): Adaptations in pre- and postsynaptic 5-HT1A receptor function and cocaine supersensitivity in serotonin transporter knockout rats. Psychopharmacology (Berl.) 200:367-380.
44. Hull EM (2011): Sex, drugs and gluttony: How the brain controls motivated behaviors. Physiol Behav 104:173-177.
45. Kagerer S, Klucken T, Wehrum S, Zimmermann M, Schienle A, Walter B, Vaitl D, Stark R (2011): Neural activation toward erotic stimuli in homosexual and heterosexual males. J Sex Med 8:3132-3143.
46. Kalisch R (2009): The functional neuroanatomy of reappraisal: Time matters. Neurosci Biobehav Rev 33:1215-1226.
47. Karama S, Lecours AR, Leroux J, Bourgouin P, Beaudoin G, Joubert S, Beauregard M (2002): Areas of brain activation in males and females during viewing of erotic film excerpts. Hum Brain Mapp 16:1-13.
48. Karg K, Burmeister M, Shedden K, Sen S (2011): The serotonin transporter promoter variant (5-HTTLPR), stress, and depression meta-analysis revisited: Evidence of genetic moderation. Arch Gen Psychiatry 68:444-454.
49. Kirsch P, Schienle A, Stark R, Sammer G, Blecker C, Walter B, Ott U, Burkart J, Vaitl D (2003): Anticipation of reward in a nonaversive differential conditioning paradigm and the brain reward system: An event-related fMRI study. NeuroImage 20:1086-1095.
50. Klucken T., Alexander N., Schweckendiek J., Merz C. J., Kagerer S., Osinsky R, et al. (in press). Individual differences in neural correlates of fear conditioning as a function of 5-HTTLPR and stressful life events. Social cognitive and affective neuroscience, doi: 10.1093/scan/nss005.
51. Klucken T, Kagerer S, Schweckendiek J, Tabbert K, Vaitl D, Stark R (2009a): Neural, electrodermal and behavioral response patterns in contingency aware and unaware subjects during a picture-picture conditioning paradigm. Neuroscience 158:721-731.
52. Klucken T, Schweckendiek J, Merz CJ, Tabbert K, Walter B, Kagerer S, Vaitl D, Stark R (2009b): Neural activations of the acquisition of conditioned sexual arousal: Effects of contingency awareness and sex. J Sex Med 6:3071-3085.
53. Klucken T, Tabbert K, Schweckendiek J, Merz CJ, Kagerer S, Vaitl D, Stark R (2009c): Contingency learning in human fear conditioning involves the ventral striatum. Hum Brain Mapp 30:3636-3644.
54. Klucken T, Schweckendiek J, Koppe G, Merz CJ, Kagerer S, Walter B, Sammer G, Vaitl D, Stark R (2012): Neural correlates of disgust- and fear-conditioned responses. Neuroscience 201:209-218.
55. Knight DC, Waters NS, Bandettini PA (2009): Neural substrates of explicit and implicit fear memory. NeuroImage 45:208-214.
56. Kranz GS, Kasper S, Lanzenberger R (2010): Reward and the serotonergic system. Neuroscience 166:1023-1035.
57. Kühn S, Gallinat J (2011): A quantitative meta-analysis on cue-induced male sexual arousal. J Sex Med 8:2269-2275.
58. Lemogne C, Gorwood P, Boni C, Pessiglione M, Lehéricy S, Fossati P (2011): Cognitive appraisal and life stress moderate the effects of the 5-HTTLPR polymorphism on amygdala reactivity. Hum Brain Mapp 32:1856-1867.
59. Lerman C, Caporaso NE, Audrain J, Main D, Boyd NR, Shields PG (2000): Interacting effects of the serotonin transporter gene and neuroticism in smoking practices and nicotine dependence. Mol Psychiatry 5:189-192.
60. Lesch KP, Bengel D, Heils A, Sabol SZ, Greenberg BD, Petri S, Benjamin J, Müller CR, Hamer DH, Murphy DL (1996): Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 274:1527-1531.
61. Lonsdorf TB, Weike AI, Nikamo P, Schalling M, Hamm AO, Ohman A (2009): Genetic gating of human fear learning and extinction: possible implications for gene-environment interaction in anxiety disorder. Psychol Sci 20:198-206.
62. Martin-Soelch C, Linthicum J, Ernst M (2007): Appetitive conditioning: Neural bases and implications for psychopathology. Neurosci Biobehav Rev 31:426-440.
63. Mechias M, Etkin A, Kalisch R (2010): A meta-analysis of instructed fear studies: Implications for conscious appraisal of threat. NeuroImage 49:1760-1768.
64. Merz CJ, Tabbert K, Schweckendiek J, Klucken T, Vaitl D, Stark R, Wolf OT (2010): Investigating the impact of sex and cortisol on implicit fear conditioning with fMRI. Psychoneuroendocrinology 35:33-46.
65. Merz CJ, Tabbert K, Schweckendiek J, Klucken T, Vaitl D, Stark R, Wolf OT: Neuronal correlates of extinction learning are modulated by sex hormones. Soc Cogn Affect Neurosci (in press). doi: 10.1093/scan/NSR063.
66. Milad MR, Quirk GJ, Pitman RK, Orr SP, Fischl B, Rauch SL (2007): A role for the human dorsal anterior cingulate cortex in fear expression. Biol Psychiatry 62:1191-1194.
67. Milad MR, Zeidan MA, Contero A, Pitman RK, Klibanski A, Rauch SL, Goldstein JM (2010): The influence of gonadal hormones on conditioned fear extinction in healthy humans. Neuroscience 168:652-658.
68. Morey RA, Hariri AR, Gold AL, Hauser MA, Munger HJ, Dolcos F, McCarthy G (2011): Serotonin transporter gene polymorphisms and brain function during emotional distraction from cognitive processing in posttraumatic stress disorder. BMC Psychiatry 11:76.
69. Munafò MR, Brown SM, Hariri AR (2008): Serotonin transporter (5-HTTLPR) genotype and amygdala activation: A meta-analysis. Biol Psychiatry 63:852-857.
70. Murrough JW, Charney DS (2011): The serotonin transporter and emotionality: Risk, resilience, and new therapeutic opportunities. Biol Psychiatry 69:510-512.
71. Nielsen F, Hansen LK (2002): Automatic anatomical labeling of Talairach coordinates and generation of volumes of interest via the BrainMap database. NeuroImage (16 (2)). Presented at the 8th International Conference on Functional Mapping of the Human Brain. Available on CD-Rom.
72. O'Doherty JP (2007): Lights, camembert, action! The role of human orbitofrontal cortex in encoding stimuli, rewards, and choices. Ann NY Acad Sci 1121:254-272.
73. Ortigue S, Bianchi-Demicheli F, Patel N, Frum C, Lewis JW (2010): Neuroimaging of love: fMRI meta-analysis evidence toward new perspectives in sexual medicine. J Sex Med 7:3541-3552.
74. Peciña S (2008): Opioid reward 'liking' and 'wanting' in the nucleus accumbens. Physiol Behav 94:675-680.
75. Penny WD, Henson R (2007): Analysis of variance. In: Friston KJ, Ashburner JT, Kiebel S, Nichols T, Penny WD, editors.Statistical parametric mapping: The analysis of functional brain images.Amsterdam:Elsevier Acad. Press. pp166-178.
76. Pérez-Edgar K, Bar-Haim Y, McDermott JM, Gorodetsky E, Hodgkinson CA, Goldman D, Ernst M, Pine DS, Fox NA (2010): Variations in the serotonin-transporter gene are associated with attention bias patterns to positive and negative emotion faces. Biol Psychol 83:269-271.
77. Pfaus JG (2009): Pathways of sexual desire. J Sex Med 6:1506-1533.
78. Phelps EA, Delgado MR, Nearing KI, LeDoux JE (2004): Extinction Learning in Humans: Role of the amygdala and vmPFC. Neuron 43:897-905.
79. Pineles SL, Orr MR, Orr SP (2009): An alternative scoring method for skin conductance responding in a differential fear conditioning paradigm with a long-duration conditioned stimulus. Psychophysiology 46:984-995.
80. Risch N, Herrell R, Lehner T, Liang K, Eaves L, Hoh J, Griem A, Kovacs M, Ott J, Merikangas KR (2009): Interaction between the serotonin transporter gene (5-HTTLPR), stressful life events, and risk of depression: A meta-analysis. JAMA 301:2462-2471.
81. Rodriguez G, Hall G (2008): Potentiation of latent inhibition. J Exp Psychol Anim Behav Process 34:352-360.
82. Rolls ET (2004): The functions of the orbitofrontal cortex. Brain Cogn 55:11-29.
83. Schardt DM, Erk S, Nüsser C, Nöthen MM, Cichon S, Rietschel M, Treutlein J, Goschke T, Walter H (2010): Volition diminishes genetically mediated amygdala hyperreactivity. NeuroImage 53:943-951.
84. Schiller D, Delgado MR (2010): Overlapping neural systems mediating extinction, reversal and regulation of fear. Trends Cogn Sci 14:268-276.
85. Schiller D, Levy I, Niv Y, LeDoux JE, Phelps EA (2008): From fear to safety and back: Reversal of fear in the human brain. J Neurosci 28:11517-11525.
86. Schweckendiek J, Klucken T, Merz CJ, Tabbert K, Walter B, Ambach W, Vaitl D, Stark R (2011): Weaving the (neuronal) web: Fear learning in spider phobia. NeuroImage 54:681-688.
87. Stoltenberg SF, Twitchell GR, Hanna GL, Cook EH, Fitzgerald HE, Zucker RA, Little KY (2002): Serotonin transporter promoter polymorphism, peripheral indexes of serotonin function, and personality measures in families with alcoholism. Am J Med Genet 114:230-234.
88. Tabbert K, Merz CJ, Klucken T, Schweckendiek J, Vaitl D, Wolf OT, Stark R (2011): Influence of contingency awareness on neural, electrodermal and evaluative responses during fear conditioning. Soc Cogn Affect Neurosci 6:495-506.
89. Turnock M, Becker S (2008): A neural network model of hippocampal-striatal-prefrontal interactions in contextual conditioning. Brain Res 1202:87-98.
90. Uher R (2008): The implications of gene-environment interactions in depression: Will cause inform cure?Mol Psychiatry 13:1070-1078.
91. Uher R, McGuffin P (2008): The moderation by the serotonin transporter gene of environmental adversity in the aetiology of mental illness: Review and methodological analysis. Mol Psychiatry 13:131-146.
92. van der Zwaluw CS, Engels RCME, Vermulst AA, Rose RJ, Verkes RJ, Buitelaar J, Franke B, Scholte RHJ (2010): A serotonin transporter polymorphism (5-HTTLPR) predicts the development of adolescent alcohol use. Drug Alcohol Depend 112:134-139.
93. Vytal K, Hamann S (2010): Neuroimaging support for discrete neural correlates of basic emotions: A voxel-based meta-analysis. J Cogn Neurosci 22:2864-2885.
94. Walter B, Blecker C, Kirsch P, Sammer G, Schienle A, Stark R, Vaitl D. (2003): MARINA: An easy to use tool for the creation of Masks for Region of Interest Analyses. 9th International Conference on Functional Mapping of the Human Brain. Available on CD-Rom in NeuroImage, Vol. 19, No. 2.
95. Way BM, Taylor SE (2010): The serotonin transporter promoter polymorphism is associated with cortisol response to psychosocial stress. Biol Psychiatry 67:487-492.