Functional neuroimaging of genetic variation in serotonergic neurotransmission

Genes, Brain and Behavior

Volumn 2, Issue 6, 2003, Pages 341-349

  Hariri, A R ^b   Weinberger, D R ^a  

^a NATIONAL INSTITUTE OF MENTAL HEALTH   (United States)

^b UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

Author keywords

Amygdala; Emotion; FMRI; PET; Prefrontal cortex; Serotonin

Indexed keywords

AMINE OXIDASE (FLAVIN CONTAINING); AMINO ACID DECARBOXYLASE; RECEPTOR SUBTYPE; SEROTONIN; SEROTONIN RECEPTOR; SEROTONIN TRANSPORTER; TRYPTOPHAN HYDROXYLASE;

AMYGDALOID NUCLEUS; BRAIN MAPPING; DNA POLYMORPHISM; ELECTROENCEPHALOGRAPHY; EMOTIONALITY; ENVIRONMENTAL FACTOR; GENE FUNCTION; GENE INTERACTION; GENETIC ASSOCIATION; GENETIC CORRELATION; GENETIC POLYMORPHISM; GENETIC RISK; GENETIC SUSCEPTIBILITY; GENETIC VARIABILITY; GENOMICS; GENOTYPE ENVIRONMENT INTERACTION; HUMAN; MAGNETOENCEPHALOGRAPHY; MENTAL DISEASE; MOOD DISORDER; NEUROMODULATION; NEUROPHYSIOLOGY; NEUROSIS; NEUROTRANSMISSION; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; PHENOMENOLOGY; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN POLYMORPHISM; PSYCHIATRIC DIAGNOSIS; REVIEW; RISK FACTOR; SEROTONINERGIC SYSTEM; TEMPERAMENT;

EID: 0344874714     PISSN: 16011848     EISSN: None     Source Type: Journal    
DOI: 10.1046/j.1601-1848.2003.00048.x     Document Type: Review

References (79)

1. Abbar, M., Courtet, P., Bellivier, F., Leboyer, M., Boulenger, J.P., Castelhau, D., Ferreira, M., Lambercy, C., Mouthon, D., Paoloni-Giacobino, A., Vessaz, M., Malafosse, A. & Buresi, C. (2001) Suicide attempts and the tryptophan hydroxylase gene. Mol Psychiatry 6, 268-273.
2. Azmitia, E.C. & Gannon, P.J. (1986) The primate serotonergic system: a review of human and animal studies and a report on Macaca fascicularis. Adv Neurol 43, 407-468.
3. Ball, D., Hill, L., Freeman, B., Eley, T.C., Strelau, J., Riemann, R., Spinath, F.M., Angleitner, A. & Plomin, R. (1997) The serotonin transporter gene and peer-rated neuroticism. Neuroreport 8, 1301-1304.
4. Bannon, M.J., Michelhaugh, S.K., Wang, J. & Sacchetti, P. (2001) The human dopamine transporter gene: gene organization, transcriptional regulation, and potential involvement in neuropsychiatric disorders. Eur Neuropsychopharmacol 11, 449-455.
5. Beauregard, M., Levesque, J. & Bourgouin, P. (2001) Neural correlates of conscious self-regulation of emotion. J Neurosci 21, RC165.
6. Bennett, A.J., Lesch, K.P., Heils, A., Long, J.C., Lorenz, J.G., Shoaf, S.E., Champoux, M., Suomi, S.J., Linnoila, M.V. & Higley, J.D. (2002) Early experience and serotonin transporter gene variation interact to influence primate CNS function. Mol Psychiatry 7, 118-122.
7. Birn, R.M., Cox, R.W. & Bandettini, P.A. (2002) Detection versus estimation in event-related fMRI: choosing the optimal stimulus timing. Neuroimage 15, 252-264.
8. Blier, P. & de Montigny, C. (1999) Serotonin and drug-induced therapeutic responses in major depression, obsessive-compulsive and panic disorders. Neuropsychopharmacology 21, 91S-98S.
9. Borglum, A.D., Bruun, T.G., Kjeldsen, T.E., Ewald, H., Mors, O., Kirov, G., Russ, C., Freeman, B., Collier, D.A. & Kruse, T.A. (1999) Two novel variants in the DOPA decarboxylase gene: association with bipolar affective disorder. Mol Psychiatry 4, 545-551.
10. Caspi, A., McClay, J., Moffitt, T.E., Mill, J., Martin, J., Craig, I.W., Taylor, A. & Poulton, R. (2002) Role of genotype in the cycle of violence in maltreated children. Science 297, 851-854.
11. Caspi, A., Sugden, K., Moffitt, T.E., Taylor, A., Craig, I.W., Harrington, H., McClay, J., Mill, J., Martin, J., Braithwaite, A. & Poulton, R. (2003) Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 301, 386-389.
12. Champoux, M., Bennett, A., Shannon, C., Higley, J.D., Lesch, K.P. & Suomi, S.J. (2002) Serotonin transporter gene polymorphism, differential early rearing, and behavior in rhesus monkey neonates. Mol Psychiatry 7, 1058-1063.
13. Darwin, C. (1998) The Expression of the Emotions in Man and Animals. Oxford University Press, Oxford.
14. Davis, M. & Whalen, P.J. (2001) The amygdala: vigilance and emotion. Mol Psychiatry 6, 13-34.
15. Deary, I. J., Battersby, S., Whiteman, M.C., Connor, J.M., Fowkes, F.G. & Harmar, A. (1999) Neuroticism and polymorphisms in the serotonin transporter gene. Psychol Med 29, 735-739.
16. Du, L., Bakish, D. & Hrdina, P.D. (2000) Gender differences in association between serotonin transporter gene polymorphism and personality traits. Psychiatr Genet 18, 159-164.
17. Eggers, B., Hermann, W., Barthel, H., Sabri, O., Wagner, A. & Hesse, S. (2003) The degree of depression in Hamilton rating scale is correlated with the density of presynaptic serotonin transporters in 23 patients with Wilson's disease. J Neurol 250, 576-580.
18. Flory, J.D., Manuck, S.B., Ferrell, R.E., Dent, K.M., Peters, D.G. & Muldoon, M.F. (1999) Neuroticism is not associated with the serotonin transporter (5-HTTLPR) polymorphism. Mol Psychiatry 4, 93-96.
19. 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.
20. Gelernter, J., Kranzler, H. & Cubells, J.F. (1997) Serotonin transporter protein (SLC6A4) allele and haplotype frequencies and linkage disequilibria in African- and European-American and Japanese populations and in alcohol-dependent subjects. Hum Genet 101, 243-246.
21. Glatt, C.E. & Freimer, N.B. (2002) Association analysis of candidate genes for neuropsychiatric disease: the perpetual campaign. Trends Genet 18, 307-312.
22. Groenink, L., Pattij, T., De Jongh, R., Van der Gugten, J., Oosting, R.S., Dirks, A. & Olivier, B. (2003) 5-HT (1A) receptor knockout mice and mice overexpressing corticotropin-releasing hormone in models of anxiety. Eur J Pharmacol 463, 185-197.
23. Gross, C., Zhuang, X., Stark, K., Ramboz, S., Oosting, R., Kirby, L., Santarelli, L., Beck, S. & Hen, R. (2002) Serotonin1A receptor acts during development to establish normal anxiety-like behaviour in the adult. Nature 416, 396-400.
24. Hagberg, G.E., Torstenson, R., Marteinsdottir, I., Fredrikson, M., Langstrom, B. & Blomqvist, G. (2002) Kinetic compartment modeling of [11C]-5-hydroxy-1-tryptophan for positron emission tomography assessment of serotonin synthesis in human brain. J Cereb Blood Flow Metab 22, 1352-1366.
25. Hariri, A.R., Bookheimer, S.Y. & Mazziotta, J.C. (2000) Modulating emotional responses: effects of a neocortical network on the limbic system. Neuroreport 11, 43-48.
26. Hariri, A.R., Mattay, V.S., Tessitore, A., Fera, F., Smith, W.G. & Weinberger, D.R. (2002a) Dextroamphetamine modulates the response of the human amygdala. Neuropsychopharmacology 27, 1036-1040.
27. Hariri, A.R., Mattay, V.S., Tessitore, A., Fera, F. & Weinberger, D.R. (2003) Neocortical modulation of the amygdala response to fearful stimuli. Biol Psychiatry 53, 494-501.
28. Hariri, A.R., Mattay, V.S., Tessitore, A., Kolachana, B., Fera, F., Goldman, D., Egan, M.F. & Weinberger, D.R. (2002b) Serotonin transporter genetic variation and the response of the human amygdala. Science 297, 400-403.
29. Hariri, A.R., Tessitore, A., Mattay, V.S., Fera, F. & Weinberger, D.R. (2002c) The amygdala response to emotional stimuli: a comparison of faces and scenes. Neuroimage 17, 317-323.
30. Hariri, A.R. & Weinberger, D.R. (2003) Imaging genomics. Br Med Bull 65, 237-248.
31. Heils, A., Teufel, A., Petri, S., Stober, G., Riederer, P., Bengel, D. & Lesch, K.P. (1996) Allelic variation of human serotonin transporter gene expression. J Neurochem 66, 2621-2624.
32. Heinz, A., Higley, J.D., Gorey, J.G., Saunders, R.C., Jones, D.W., Hommer, D., Zajicek, K., Suomi, S.J., Lesch, K.P., Weinberger, D.R. & Linnoila, M. (1998) In vivo association between alcohol intoxication, aggression, and serotonin transporter availability in nonhuman primates. Am J Psychiatry 155, 1023-1028.
33. Heinz, A., Jones, D.W., Bissette, G., Hommer, D., Ragan, P., Knable, M., Wellek, S., Linnoila, M. & Weinberger, D.R. (2002) Relationship between cortisol and serotonin metabolites and transporters in alcoholism [correction of alcolholism]. Pharmacopsychiatry 35, 127-134.
34. Heinz, A., Jones, D.W., Mazzanti, C., Goldman, D., Ragan, P., Hommer, D., Linnoila, M. & Weinberger, D.R. (2000) A relationship between serotonin transporter genotype and in vivo protein expression and alcohol neurotoxicity. Biol Psychiatry 47, 643-649.
35. Holmes, A., Yang, R.J., Lesch, K.P., Crawley, J.N. & Murphy, D.L. Mice lacking the serotonin transporter exhibit 5-HT1A receptor-mediated abnormalities in anxiety-like and exploratory behavior. Neuropsychoparmacology in press.
36. ume, S., Hirani, E., Opacka-Juffry, J., Myers, R., Townsend, C., Pike, V. & Grasby, P. (2001) Effect of 5-HT on binding of [(11) C] WAY 100635-5-HT (IA) receptors in rat brain, assessed using in vivo microdialysis and PET after fenfluramine. Synapse 41, 150-159.
37. Katsuragi, S., Kunugi, H., Sano, A., Tsutsumi, T., Isogawa, K., Nanko, S. & Akiyoshi, J. (1999) Association between serotonin transporter gene polymorphism and anxiety-related traits. Biol Psychiatry 45, 368-370.
38. Keightley, M.L., Winocur, G., Graham, S.J., Mayberg, H.S., Hevenor, S.J. & Grady, C.L. (2003) An fMRI study investigating cognitive modulation of brain regions associated with emotional processing of visual stimuli. Neuropsychologia 41, 585-596.
39. Lange, K., Williams, L.M., Young, A.W., Bullmore, E.T., Brammer, M.J., Williams, S.C., Gray, J.A. & Phillips, M.L. (2003) Task instructions modulate neural responses to fearful facial expressions. Biol Psychiatry 53, 226-232.
40. LeDoux, J. (1997) The Emotional Brain. Simon and Schuster, New York.
41. Lesch, K.P., Bengel, D., Heils, A., Sabol, S.Z., Greenberg, B.D., Petri, S., Benjamin, J., Muller, C.R., Hamer, D.H. & Murphy, D.L. (1996) Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 274, 1527-1531.
42. Lesch, K.P. & Mossner, R. (1998) Genetically driven variation in serotonin uptake: is there a link to affective spectrum, neurodevelopmental, and neurodegenerative disorders? Biol Psychiatry 44, 179-192.
43. Li, Q., Wichems, C., Heils, A., Lesch, K.P. & Murphy, D.L. (2000) Reduction in the density and expression, but not G-protein coupling, of serotonin receptors (5-HT1A) in 5-HT transporter knock-out mice: gender and brain region differences. J Neurosci 20, 7888-7895.
44. Li, Q., Wichems, C., Heils, A., Van De Kar, L.D., Lesch, K.P. & Murphy, D.L. (1999) Reduction of 5-hydroxytryptamine (5-HT) (1A)-mediated temperature and neuroendocrine responses and 5-HT (1A) binding sites in 5-HT transporter knockout mice. J Pharmacol Exp Ther 291, 999-1007.
45. Little, K.Y., McLaughlin, D.P., Zhang, L., Livermore, C.S., Dalack, G.W., De McFinton, P.R.I., Proposto, Z.S., Hill, E., Cassin, B.J., Watson, S.J. & Cook, E.H. (1998) Cocaine, ethanol, and genotype effects on human midbrain serotonin transporter binding sites and mRNA levels. Am J Psychiatry 155, 207-213.
46. Lucki, I. (1998) The spectrum of behaviors influenced by serotonin. Biol Psychiatry 44, 151-162.
47. Malison, R.T., Price, L.H., Berman, R., van Dyck, C.H., Pelton, G.H., Carpenter, L., Sanacora, G., Owens, M.J., Nemeroff, C.B., Rajeevan, N., Baldwin, R.M., Seibyl, J.P., Innis, R.B. & Charney, D.S. (1998) Reduced brain serotonin transporter availability in major depression as measured by [123I]-2 beta-carbomethoxy-3 beta-(4-iodophenyl) tropane and single photon emission computed tomography. Biol Psychiatry 44, 1090-1098.
48. Manuck, S.B., Flory, J.D., Ferrell, R.E., Mann, J.J. & Muldoon, M.F. (2000) A regulatory polymorphism of the monoamine oxidase-A gene may be associated with variability in aggression, impulsivity, and central nervous system serotonergic responsivity. Psychiatry Res 95, 9-23.
49. Manuck, S.B., Flory, J.D., Muldoon, M.F. & Ferrell, R.E. (2002) Central nervous system serotonergic responsivity and aggressive disposition in men. Physiol Behav 77, 705-709.
50. Mathis, C.A., Simpson, N.R., Mahmood, K., Kinahan, P.E. & Mintun, M.A. (1994) [11C]WAY 100635: a radioligand for imaging 5-HT1A receptors with positron emission tomography. Life Sci 55, PL403-407.
51. Mazzanti, C.M., Lappalainen, J., Long, J.C., Bengel, D., Naukkarinen, H., Eggert, M., Virkkunen, M., Linnoila, M. & Goldman, D. (1998) Role of the serotonin transporter promoter polymorphism in anxiety-related traits. Arch General Psychiatry 55, 936-940.
52. Melke, J., Landen, M., Baghei, F., Rosmond, R., Holm, G., Bjorntorp, P., Westberg, L., Hellstrand, M. & Eriksson, E. (2001) Serotonin transporter gene polymorphisms are associated with anxiety-related personality traits in women. Am J Med Genet 105, 458-463.
53. Meyer, J.H., Wilson, A.A., Ginovart, N., Goulding, V., Hussey, D., Hood, K. & Houle, S. (2001) Occupancy of serotonin transporters by paroxetine and citalopram during treatment of depression: a [(11) C]DASB PET imaging study. Am J Psychiatry 158, 1843-1849.
54. Moreno, F.A., Rowe, D.C., Kaiser, B., Chase, D., Michaels, T., Gelernter, J. & Delgado, P.L. (2002) Association between a serotonin transporter promoter region polymorphism and mood response during tryptophan depletion. Mol Psychiatry 7, 213-216.
55. Murphy, D.L., Andrews, A.M., Wichems, C.H., Li, Q., Tohda, M. & Greenberg, B. (1998) Brain serotonin neurotransmission: an overview and update with an emphasis on serotonin subsystem heterogeneity, multiple receptors, interactions with other neurotransmitter systems, and consequent implications for understanding the actions of serotonergic drugs. J Clin Psychiatry 59, 4-12.
56. Nakamura, K., Kawashima, R., Ito, K., Sugiura, M., Kato, T., Nakamura, A., Hatano, K., Nagumo, S., Kubota, K., Fukuda, H. & Kojima, S. (1999) Activation of the right inferior frontal cortex during assessment of facial emotion. J Neurophysiol 82, 1610-1614.
57. Narumoto, J., Yamada, H., Iidaka, T., Sadato, N., Fukui, K., Itoh, H. & Yonekura, Y. (2000) Brain regions involved in verbal or non-verbal aspects of facial emotion recognition. Neuroreport 11, 2571-2576.
58. Neumeister, A., Konstantinidis, A., Stastny, J., Schwarz, M.J., Vitouch, O., Willeit, M., Praschak-Rieder, N., Zach, J., de Zwaan, M., Bondy, B., Ackenheil, M. & Kasper, S. (2002) Association between serotonin transporter gene promoter polymorphism (5HTTLPR) and behavioral responses to tryptophan depletion in healthy women with and without family history of depression. Arch General Psychiatry 59, 613-620.
59. Nielsen, D.A., Goldman, D., Virkkunen, M., Tokola, R., Rawlings, R. & Linnoila, M. (1994) Suicidality and 5-hydroxyindoleacetic acid concentration associated with a tryptophan hydroxylase polymorphism. Arch General Psychiatry 51, 34-38.
60. Nielsen, D.A., Jenkins, G.L., Stefanisko, K.M., Jefferson, K.K. & Goldman, D. (1997) Sequence, splice site and population frequency distribution analyses of the polymorphic human tryptophan hydroxylase intron 7. Brain Res Mol Brain Res 45, 145-148.
61. Nielsen, D.A., Virkkunen, M., Lappalainen, J., Eggert, M., Brown, G.L., Long, J.C., Goldman, D. & Linnoila, M. (1998) A tryptophan hydroxylase gene marker for suicidality and alcoholism. Arch General Psychiatry 55, 593-602.
62. Nolan, K.A., Volavka, J., Lachman, H.M. & Saito, T. (2000) An association between a polymorphism of the tryptophan hydroxylase gene and aggression in schizophrenia and schizoaffective disorder. Psychiatr Genet 10, 109-115.
63. Ohara, K., Nagai, M., Tsukamoto, T., Tani, K. & Suzuki, Y. (1998) Functional polymorphism in the serotonin transporter promoter at the SLC6A4 locus and mood disorders. Biol Psychiatry 44, 550-554.
64. Parsey, R.V., Oquendo, M.A., Simpson, N.R., Ogden, R.T., Van Heertum, R., Arango, V. & Mann, J.J. (2002) Effects of sex, age, and aggressive traits in man on brain serotonin 5-HT1A receptor binding potential measured by PET using [C-11]WAY-100635. Brain Res 954, 173-182.
65. Reif, A. & Lesch, K.P. (2003) Toward a molecular architecture of personality. Behav Brain Res 139, 1-20.
66. Salichon, N., Gaspar, P., Upton, A.L., Picaud, S., Hanoun, N., Hamon, M., De Maeyer, E., Murphy, D.L., Mossner, R., Lesch, K.P., Hen, R. & Seif, I. (2001) Excessive activation of serotonin (5-HT) 1B receptors disrupts the formation of sensory maps in monoamine oxidase a and 5-ht transporter knock-out mice. J Neurosci 21, 884-896.
67. Sandell, J., Halldin, C., Sovago, J., Chou, Y.H., Gulyas, B., Yu, M., Emond, P., Nagren, K., Guilloteau, D. & Farde, L. (2002) PET examination of [(11) C]5-methyl-6-nitroquipazine, a radioligand for visualization of the serotonin transporter. Nucl Med Biol 29, 651-656.
68. Sora, I., Hall, F.S., Andrews, A.M., Itokawa, M., Li, X.F., Wei, H.B., Wichems, C., Lesch, K.P., Murphy, D.L. & Uhl, G.R. (2001) Molecular mechanisms of cocaine reward: combined dopamine and serotonin transporter knockouts eliminate cocaine place preference. Proc Natl Acad Sci U S A 98, 5300-5305.
69. Szabo, Z., Scheffel, U., Mathews, W.B., Ravert, H.T., Szabo, K., Kraut, M., Palmon, S., Ricaurte, G.A. & Dannals, R.F. (1999) Kinetic analysis of [11C]McN5652: a serotonin transporter radioligand. J Cereb Blood Flow Metab 19, 967-981.
70. Tessitore, A., Hariri, A.R., Fera, F., Smith, W.G., Chase, T.N., Hyde, T.M., Weinberger, D.R. & Mattay, V.S. (2002) Dopamine modulates the response of the human amygdala: a study in Parkinson's disease. J Neurosci 22, 9099-9103.
71. Upton, A.L., Ravary, A., Salichon, N., Moessner, R., Lesch, K.P., Hen, R., Seif, I. & Gaspar, P. (2002) Lack of 5-HT (1B) receptor and of serotonin transporter have different effects on the segregation of retinal axons in the lateral geniculate nucleus compared to the superior colliculus. Neuroscience 111, 597-610.
72. Walther, D.J., Peter, J.U., Bashammakh, S., Hortnagl, H., Voits, M., Fink, H. & Bader, M. (2003) Synthesis of serotonin by a second tryptophan hydroxylase isoform. Science 299, 76.
73. Whale, R., Quested, D.J., Laver, D., Harrison, P.J. & Cowen, P.J. (2000) Serotonin transporter (5-HTT) promoter genotype may influence the prolactin response to clomipramine. Psychopharmacology (Berl) 150, 120-122.
74. Willeit, M., Praschak-Rieder, N., Neumeister, A., Pirker, W., Asenbaum, S., Vitouch, O., Tauscher, J., Hilger, E., Stastny, J., Brucke, T. & Kasper, S. (2000) [123I]-beta-CIT SPECT imaging shows reduced brain serotonin transporter availability in drug-free depressed patients with seasonal affective disorder. Biol Psychiatry 47, 482-489.
75. Williams, R.B., Marchuk, D.A., Gadde, K.M., Barefoot, J.C., Grichnik, K., Helms, M.J., Kuhn, C.M., Lewis, J.G., Schanberg, S.M., Stafford-Smith, M., Suarez, E.C., Clary, G.L., Svenson, I.K. & Siegler, I.C. (2003) Serotonin-related gene polymorphisms and central nervous system serotonin function. Neuropsychopharmacology 28, 533-541.
76. Wilson, A.A., Ginovart, N., Schmidt, M., Meyer, J.H., Threlkeld, P.G. & Houle, S. (2000) Novel radiotracers for imaging the serotonin transporter by positron emission tomography: synthesis, radiosynthesis, and in vitro and ex vivo evaluation of (11) C-labeled 2-(phenylthio) araalkylamines. J Med Chem 43, 3103-3110.
77. Zald, D.H. (2003) The human amygdala and the emotional evaluation of sensory stimuli. Brain Res Brain Res Rev 41, 88-123.
78. Zhou, F.C., Lesch, K.P. & Murphy, D.L. (2002) Serotonin uptake into dopamine neurons via dopamine transporters: a compensatory alternative. Brain Res 942, 109-119.
79. Zimmer, L., Mauger, G., Le Bars, D., Bonmarchand, G., Luxen, A. & Pujol, J.F. (2002) Effect of endogenous serotonin on the binding of the 5-hT1A PET ligand 18F-MPPF in the rat hippocampus: kinetic beta measurements combined with microdialysis. J Neurochem 80, 278-286.