Serotonin synthesis and reuptake in social anxiety disorder a positron emission tomography study

JAMA Psychiatry

Volumn 72, Issue 8, 2015, Pages 794-802

  Frick, Andreas ^a   Åhs, Fredrik ^a,b   Engman, Jonas ^a   Jonasson, My ^a   Alaie, Iman ^a   Björkstrand, Johannes ^a   Frans, Örjan ^a   Faria, Vanda ^a,c   Linnman, Clas ^a,c   Appel, Lieuwe ^a   Wahlstedt, Kurt ^a   Lubberink, Mark ^a   Fredrikson, Mats ^a,b   Furmark, Tomas ^a  

^a UPPSALA UNIVERSITY   (Sweden)

^b KAROLINSKA INSTITUTE   (Sweden)

^c HARVARD MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

3 AMINO 4 (2 DIMETHYLAMINOMETHYLPHENYLSULFANYL) BENZONITRILE C 11; 5 HYDROXYTRYPTOPHAN C 11; RADIOPHARMACEUTICAL AGENT; SEROTONIN TRANSPORTER; UNCLASSIFIED DRUG; 5 HYDROXYTRYPTOPHAN; BENZYLAMINE DERIVATIVE; CARBON; N,N-DIMETHYL-2-(2-AMINO-4-CYANOPHENYLTHIO)BENZYLAMINE; SEROTONIN;

ADULT; ANTERIOR CINGULATE; ARTICLE; CAUDATE NUCLEUS; CLINICAL ARTICLE; CONTROLLED STUDY; CROSS-SECTIONAL STUDY; DSM-IV-TR; FEMALE; HIPPOCAMPUS; HUMAN; ISOTOPE LABELING; LIEBOWITZ SOCIAL ANXIETY SCALE; MALE; MINI INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; PATHOGENESIS; PET SCANNER; POSITRON EMISSION TOMOGRAPHY; PROTEIN SYNTHESIS; PUTAMEN; RAPHE NUCLEUS; SEROTONIN SYNTHESIS; SEX RATIO; SOCIAL PHOBIA; THALAMUS; VOLUME OF DISTRIBUTION RATIO; ANXIETY DISORDER; BIOSYNTHESIS; BRAIN; CASE CONTROL STUDY; DIAGNOSTIC USE; FUNCTIONAL NEUROIMAGING; METABOLISM; PHOBIA; SOCIAL BEHAVIOR; YOUNG ADULT;

5-HYDROXYTRYPTOPHAN; ADULT; ANXIETY DISORDERS; BENZYLAMINES; BRAIN; CARBON RADIOISOTOPES; CASE-CONTROL STUDIES; CROSS-SECTIONAL STUDIES; FEMALE; FUNCTIONAL NEUROIMAGING; HUMANS; MALE; PHOBIC DISORDERS; POSITRON-EMISSION TOMOGRAPHY; SEROTONIN; SEROTONIN PLASMA MEMBRANE TRANSPORT PROTEINS; SOCIAL BEHAVIOR; YOUNG ADULT;

EID: 84939802541     PISSN: 2168622X     EISSN: None     Source Type: Journal    
DOI: 10.1001/jamapsychiatry.2015.0125     Document Type: Article

References (73)

1. Stein MB, Kean YM. Disability and quality of life in social phobia: epidemiologic findings. Am J Psychiatry. 2000;157(10):1606-1613.
2. Whiteford HA, Degenhardt L, Rehm J, et al. Global burden of disease attributable to mental and substance use disorders: findings from the Global Burden of Disease Study 2010. Lancet. 2013;382 (9904):1575-1586.
3. Kessler RC, Berglund P, Demler O, Jin R, Merikangas KR,Walters EE. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2005;62(6):593-602.
4. Griebel G. 5-Hydroxytryptamine-interacting drugs in animal models of anxiety disorders: more than 30 years of research. Pharmacol Ther. 1995;65 (3):319-395.
5. Maron E, Nutt D, Shlik J. Neuroimaging of serotonin system in anxiety disorders. Curr Pharm Des. 2012;18(35):5699-5708.
6. van derWee NJ, van Veen JF, Stevens H, van Vliet IM, van Rijk PP,Westenberg HG. Increased serotonin and dopamine transporter binding in psychotropic medication-naive patients with generalized social anxiety disorder shown by 123I-(4-iodophenyl)-tropane SPECT. J Nucl Med. 2008;49(5):757-763.
7. Lanzenberger RR,Mitterhauser M, Spindelegger C, et al. Reduced serotonin-1A receptor binding in social anxiety disorder. Biol Psychiatry. 2007;61(9):1081-1089.
8. Boadle-Biber MC. Regulation of serotonin synthesis. Prog Biophys Mol Biol. 1993;60(1):1-15.
9. Freitas-Ferrari MC, Hallak JEC, Trzesniak C, et al. Neuroimaging in social anxiety disorder: a systematic review of the literature. Prog Neuropsychopharmacol Biol Psychiatry. 2010;34(4): 565-580.
10. Asan E, SteinkeM, Lesch K-P. Serotonergic innervation of the amygdala: targets, receptors, and implications for stress and anxiety. Histochem Cell Biol. 2013;139(6):785-813.
11. Sareen J, Campbell DW, Leslie WD, et al. Striatal function in generalized social phobia: a functional magnetic resonance imaging study. Biol Psychiatry. 2007;61(3):396-404.
12. Blanco C, Bragdon LB, Schneier FR, Liebowitz MR. The evidence-based pharmacotherapy of social anxiety disorder. Int J Neuropsychopharmacol. 2013;16(1):235-249.
13. Ipser JC, Kariuki CM, Stein DJ. Pharmacotherapy for social anxiety disorder: a systematic review. Expert Rev Neurother. 2008;8(2):235-257.
14. Baldwin DS, Anderson IM, Nutt DJ, et al. Evidence-based pharmacological treatment of anxiety disorders, post-traumatic stress disorder and obsessive-compulsive disorder: a revision of the 2005 guidelines from the British Association for Psychopharmacology. J Psychopharmacol. 2014;28 (5):403-439.
15. Phan KL, Coccaro EF, Angstadt M, et al. Corticolimbic brain reactivity to social signals of threat before and after sertraline treatment in generalized social phobia. Biol Psychiatry. 2013;73 (4):329-336.
16. Furmark T, TillforsM, Marteinsdottir I, et al. Common changes in cerebral blood flow in patients with social phobia treated with citalopram or cognitive-behavioral therapy. Arch Gen Psychiatry. 2002;59(5):425-433.
17. Furmark T, Appel L, Michelgard A, et al. Cerebral blood flow changes after treatment of social phobia with the neurokinin-1 antagonist GR205171, citalopram, or placebo. Biol Psychiatry. 2005;58(2): 132-142.
18. Faria V, Appel L, Ahs F, et al. Amygdala subregions tied to SSRI and placebo response in patients with social anxiety disorder. Neuropsychopharmacology. 2012;37(10):2222-2232.
19. Warwick JM, Carey P, Van der Linden G, et al. A comparison of the effects of citalopram and moclobemide on resting brain perfusion in social anxiety disorder. Metab Brain Dis. 2006;21(2-3): 241-252.
20. Argyropoulos SV, Hood SD, AdroverM, et al. Tryptophan depletion reverses the therapeutic effect of selective serotonin reuptake inhibitors in social anxiety disorder. Biol Psychiatry. 2004;56(7): 503-509.
21. Visser AKD, vanWaarde A, Willemsen ATM, et al. Measuring serotonin synthesis: from conventional methods to PET tracers and their (pre)clinical implications. Eur J Nucl Med Mol Imaging. 2011;38(3):576-591.
22. Hagberg GE, Torstenson R, Marteinsdottir I, Fredrikson M, Langstrom B, Blomqvist G. Kinetic compartment modeling of [11C]-5-hydroxy-Ltryptophan for positron emission tomography assessment of serotonin synthesis in human brain. J Cereb Blood Flow Metab. 2002;22(11):1352-1366.
23. Lundquist P, Blomquist G, Hartvig P, et al. Validation studies on the 5-hydroxy-L-[-11C]-tryptophan/PET method for probing the decarboxylase step in serotonin synthesis. Synapse. 2006;59(8):521-531.
24. Zhong H, Haddjeri N, Sanchez C. Escitalopram, an antidepressant with an allosteric effect at the serotonin transporter: a review of current understanding of its mechanism of action. Psychopharmacology (Berl). 2012;219(1):1-13.
25. Rhodes RA, Murthy NV, Dresner MA, et al. Human 5-HT transporter availability predicts amygdala reactivity in vivo. J Neurosci. 2007;27 (34):9233-9237.
26. Houle S, Ginovart N, Hussey D, Meyer JH, Wilson AA. Imaging the serotonin transporter with positron emission tomography: initial human studies with [11C]DAPP and [11C]DASB. Eur J Nucl Med. 2000;27(11):1719-1722.
27. Kim SW, Park SY, Hwang O. Up-regulation of tryptophan hydroxylase expression and serotonin synthesis by sertraline. Mol Pharmacol. 2002;61(4): 778-785.
28. Murrough JW, Huang Y, Hu J, et al. Reduced amygdala serotonin transporter binding in posttraumatic stress disorder. Biol Psychiatry. 2011; 70(11):1033-1038.
29. Maron E, Kuikka JT, Shlik J, Vasar V, Vanninen E, Tiihonen J. Reduced brain serotonin transporter binding in patients with panic disorder. Psychiatry Res. 2004;132(2):173-181.
30. Maron E, Toru I, Hirvonen J, et al. Gender differences in brain serotonin transporter availability in panic disorder. J Psychopharmacol. 2011;25(7):952-959.
31. Cannon DM, Klaver JM, Klug SA, et al. Gender-specific abnormalities in the serotonin transporter system in panic disorder. Int J Neuropsychopharmacol. 2013;16(4):733-743.
32. Holmes A, Murphy DL, Crawley JN. Abnormal behavioral phenotypes of serotonin transporter knockout mice: parallels with human anxiety and depression. Biol Psychiatry. 2003;54(10):953-959.
33. Furmark T, TillforsM, Everz P, Marteinsdottir I, Gefvert O, Fredrikson M. Social phobia in the general population: prevalence and sociodemographic profile. Soc Psychiatry Psychiatr Epidemiol. 1999;34(8):416-424.
34. Sheehan DV, Lecrubier Y, Sheehan KH, et al. TheMini-International Neuropsychiatric Interview (MINI): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry. 1998;59(suppl 20):22-33.
35. First MB, Gibbon M, Spitzer RL,Williams JBW. SCID-I: Interview Protocol (Swedish). Stockholm, Sweden: Pilgrim Press; 1998.
36. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed, text revision. Washington, DC: American Psychiatric Association; 2000.
37. Fresco DM, Coles ME, Heimberg RG, et al. The Liebowitz Social Anxiety Scale: a comparison of the psychometric properties of self-report and clinician-administered formats. Psychol Med. 2001; 31(6):1025-1035.
38. Agren H, Reibring L, Hartvig P, et al. Low brain uptake of L-[11C]5-hydroxytryptophan in major depression: a positron emission tomography study on patients and healthy volunteers. Acta Psychiatr Scand. 1991;83(6):449-455.
39. Innis RB, Cunningham VJ, Delforge J, et al. Consensus nomenclature for in vivo imaging of reversibly binding radioligands. J Cereb Blood Flow Metab. 2007;27(9):1533-1539.
40. Patlak CS, Blasberg RG, Fenstermacher JD. Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data. J Cereb Blood Flow Metab. 1983;3(1):1-7.
41. BergstromM, Kumlien E, Lilja A, Tyrefors N, Westerberg G, Langstrom B. Temporal lobe epilepsy visualized with PET with 11C-L-deuterium-deprenyl: analysis of kinetic data. Acta Neurol Scand. 1998;98 (4):224-231.
42. Logan J, Fowler JS, Volkow ND,Wang GJ, Ding YS, Alexoff DL. Distribution volume ratios without blood sampling from graphical analysis of PET data. J Cereb Blood Flow Metab. 1996;16(5): 834-840.
43. Meyer JH. Imaging the serotonin transporter during major depressive disorder and antidepressant treatment. J Psychiatry Neurosci. 2007;32(2):86-102.
44. Svarer C, Madsen K, Hasselbalch SG, et al. MR-based automatic delineation of volumes of interest in human brain PET images using probability maps. Neuroimage. 2005;24(4):969-979.
45. Jonasson M. Automatic definition of volumes of interest using a probability templatemethod (PVElab) without a structural MRI image. In: Poster presented at: 10th International Symposium on Functional Neuroreceptor Mapping of the Living Brain; May 23, 2014; Egmond aan Zee, the Netherlands.
46. Savli M, Bauer A, Mitterhauser M, et al. Normative database of the serotonergic system in healthy subjects using multi-tracer PET. Neuroimage. 2012;63(1):447-459.
47. Shin LM, Liberzon I. The neurocircuitry of fear, stress, and anxiety disorders. Neuropsychopharmacology. 2010;35(1):169-191.
48. Boehme S, Ritter V, Tefikow S, et al. Brain activation during anticipatory anxiety in social anxiety disorder. Soc Cogn Affect Neurosci. 2014;9 (9):1413-1418.
49. Sripada C, Angstadt M, Liberzon I,McCabe K, Phan KL. Aberrant reward center response to partner reputation during a social exchange game in generalized social phobia. Depress Anxiety. 2013; 30(4):353-361.
50. Klumpp H, Angstadt M, Phan KL. Insula reactivity and connectivity to anterior cingulate cortex when processing threat in generalized social anxiety disorder. Biol Psychol. 2012;89(1):273-276.
51. Maldjian JA, Laurienti PJ, Kraft RA, Burdette JH. An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fMRI data sets. Neuroimage. 2003;19(3):1233-1239.
52. Kessler RC, Petukhova M, Sampson NA, Zaslavsky AM, Wittchen H-U. Twelve-month and lifetime prevalence and lifetime morbid risk of anxiety and mood disorders in the United States. Int JMethods Psychiatr Res. 2012;21(3):169-184.
53. Nishizawa S, Benkelfat C, Young SN, et al. Differences between males and females in rates of serotonin synthesis in human brain. Proc Natl Acad Sci U S A. 1997;94(10):5308-5313.
54. Jovanovic H, Lundberg J, Karlsson P, et al. Sex differences in the serotonin 1A receptor and serotonin transporter binding in the human brain measured by PET. Neuroimage. 2008;39(3): 1408-1419.
55. Staley JK, Krishnan-Sarin S, Zoghbi S, et al. Sex differences in [123I]-CIT SPECT measures of dopamine and serotonin transporter availability in healthy smokers and nonsmokers. Synapse. 2001;41(4):275-284.
56. Mai JK, Assheuer J, Paxinos G. Atlas of the Human Brain. San Diego, CA: Academic Press; 1997.
57. Kalin NH, Shelton SE, Davidson RJ. The role of the central nucleus of the amygdala in mediating fear and anxiety in the primate. J Neurosci. 2004; 24(24):5506-5515.
58. Hranilovic D, Cicin-Sain L, Bordukalo-Niksic T, Jernej B. Rats with constitutionally upregulated/downregulated platelet 5HT transporter: differences in anxiety-related behavior. Behav Brain Res. 2005;165(2):271-277.
59. Bordukalo-Niksic T, Mokrovic G, Stefulj J, ZivinM, Jernej B, Cicin-Sain L. 5HT-1A receptors and anxiety-like behaviours: studies in rats with constitutionally upregulated/downregulated serotonin transporter. Behav Brain Res. 2010;213 (2):238-245.
60. Fisher PM, Meltzer CC, Ziolko SK, et al. Capacity for 5-HT1A-mediated autoregulation predicts amygdala reactivity. Nat Neurosci. 2006;9 (11):1362-1363.
61. TillforsM, Furmark T, Marteinsdottir I, Fredrikson M. Cerebral blood flow during anticipation of public speaking in social phobia: a PET study. Biol Psychiatry. 2002;52(11):1113-1119.
62. Geller I, Blum K. The effects of 5-HTP on para-chlorophenylalanine (p-CPA) attenuation of "conflict" behavior. Eur J Pharmacol. 1970;9(3): 319-324.
63. David DJP, Bourin M, Jego G, Przybylski C, Jolliet P, Gardier AM. Effects of acute treatment with paroxetine, citalopram and venlafaxine in vivo on noradrenaline and serotonin outflow: amicrodialysis study in Swissmice. Br J Pharmacol. 2003;140(6):1128-1136.
64. Drapier D, Bentue-Ferrer D, Laviolle B, et al. Effects of acute fluoxetine, paroxetine and desipramine on rats tested on the elevated plus-maze. Behav Brain Res. 2007;176(2):202-209.
65. Arrant AE, Jemal H, Kuhn CM. Adolescent male rats are less sensitive than adults to the anxiogenic and serotonin-releasing effects of fenfluramine. Neuropharmacology. 2013;65:213-222.
66. Etkin A, Egner T, Kalisch R. Emotional processing in anterior cingulate and medial prefrontal cortex. Trends Cogn Sci. 2011;15(2):85-93.
67. Nash JR, Sargent PA, Rabiner EA, et al. Serotonin 5-HT1A receptor binding in people with panic disorder: positron emission tomography study. Br J Psychiatry. 2008;193(3):229-234.
68. Neumeister A, Bain E, Nugent AC, et al. Reduced serotonin type 1A receptor binding in panic disorder. J Neurosci. 2004;24(3):589-591.
69. Berney A, LeytonM, Gravel P, et al. Brain regional -[11C]methyl-L-tryptophan trapping in medication-free patients with obsessivecompulsive disorder. Arch Gen Psychiatry. 2011;68 (7):732-741.
70. Oler JA, Fox AS, Shelton SE, et al. Serotonin transporter availability in the amygdala and bed nucleus of the stria terminalis predicts anxious temperament and brain glucose metabolic activity. J Neurosci. 2009;29(32):9961-9966.
71. Gryglewski G, Lanzenberger R, Kranz GS, Cumming P. Meta-analysis of molecular imaging of serotonin transporters in major depression. J Cereb Blood Flow Metab. 2014;34(7):1096-1103.
72. Best J, Nijhout HF, Reed M. Serotonin synthesis, release and reuptake in terminals: a mathematical model. Theor Biol Med Model. 2010; 7(1):34. doi:10. 1186/1742-4682-7-34.
73. Borue X, Condron B, Venton BJ. Both synthesis and reuptake are critical for replenishing the releasable serotonin pool in Drosophila. J Neurochem. 2010;113(1):188-199.