The impact of 5-HTTLPR on acute serotonin transporter blockade by escitalopram on emotion processing: Preliminary findings from a randomised, crossover fMRI study

Australian and New Zealand Journal of Psychiatry

Volumn 48, Issue 12, 2014, Pages 1115-1125

  Outhred, Tim ^a   Das, Pritha ^a,b   Dobson Stone, Carol ^c,d   Felmingham, Kim L ^e   Bryant, Richard A ^d   Nathan, Pradeep J ^f,g   Malhi, Gin S ^a,b   Kemp, Andrew H ^a,b,h  

^a UNIVERSITY OF SYDNEY   (Australia)

^b ROYAL NORTH SHORE HOSPITAL   (Australia)

^c NEUROSCIENCE RESEARCH AUSTRALIA   (Australia)

^d UNIVERSITY OF NEW SOUTH WALES   (Australia)

^e UNIVERSITY OF TASMANIA   (Australia)

^f UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^g MONASH UNIVERSITY   (Australia)

^h UNIVERSITY OF SÃO PAULO   (Brazil)

Author keywords

5 HTTLPR; Antidepressant; emotion; fMRI; pharmacogenetics; serotonin

Indexed keywords

ESCITALOPRAM; PLACEBO; SEROTONIN TRANSPORTER; SEROTONIN TRANSPORTER LINKED POLYMORPHIC REGION; UNCLASSIFIED DRUG; CITALOPRAM; SEROTONIN UPTAKE INHIBITOR; SLC6A4 PROTEIN, HUMAN;

ADULT; ALLELE; AMYGDALOID NUCLEUS; ARTICLE; BOLD SIGNAL; CAUCASIAN; CONTROLLED STUDY; DOUBLE BLIND PROCEDURE; EMOTION; EMOTIONALITY; FEMALE; FUNCTIONAL MAGNETIC RESONANCE IMAGING; FUNCTIONAL NEUROIMAGING; GENOTYPE; HUMAN; HUMAN EXPERIMENT; KERNEL METHOD; NORMAL HUMAN; PATIENT HEALTH QUESTIONNAIRE 9; PHARMACOGENETICS; RANDOMIZED CONTROLLED TRIAL; SINGLE DRUG DOSE; TASK PERFORMANCE; TIME TO MAXIMUM PLASMA CONCENTRATION; ADOLESCENT; BRAIN MAPPING; CROSSOVER PROCEDURE; DRUG EFFECTS; GENE DOSAGE; GENETICS; METABOLISM; NUCLEAR MAGNETIC RESONANCE IMAGING; PHYSIOLOGY; SINGLE NUCLEOTIDE POLYMORPHISM; YOUNG ADULT;

ADOLESCENT; ADULT; ALLELES; AMYGDALA; BRAIN MAPPING; CITALOPRAM; CROSS-OVER STUDIES; DOUBLE-BLIND METHOD; EMOTIONS; FEMALE; FUNCTIONAL NEUROIMAGING; GENE DOSAGE; GENOTYPE; HUMANS; MAGNETIC RESONANCE IMAGING; POLYMORPHISM, SINGLE NUCLEOTIDE; SEROTONIN PLASMA MEMBRANE TRANSPORT PROTEINS; SEROTONIN UPTAKE INHIBITORS; YOUNG ADULT;

EID: 84912030564     PISSN: 00048674     EISSN: 14401614     Source Type: Journal    
DOI: 10.1177/0004867414533837     Document Type: Article

References (79)

1. Alphapharm (2012) Loxalate: Product Information. Sydney: Alphapharm. Available from:www-mimsonline-com-au/MIMSData/en-AU/FullXML/pdf/man08076.pdf (accessed 31 January 2013).
2. Anderson IM, Del-Ben CM, McKie S, et al. Citalopram modulation of neuronal responses to aversive face emotions: A functional MRI study. Neuroreport. 2007 ; 18: 1351-1355
3. Belmaker RH, Agam G. Major depressive disorder. New England Journal of Medicine. 2008 ; 358: 55-68
4. Bennett CM, Wolford GL, Miller MB. The principled control of false positives in neuroimaging. Social Cognitive and Affective Neuroscience. 2009 ; 4: 417-422
5. Bethea CL, Lu NZ, Gundlah C, et al. Diverse actions of ovarian steroids in the serotonin neural system. Frontiers in Neuroendocrinology. 2002 ; 23: 41-100
6. Brett M, Anton J-L, Valabregue R, et al. Region of interest analysis using an SPM toolbox. 8th International Conference on Functional Mapping of the Human Brain ; 2002 Sendai, Japan ; 2002. 1140.
7. Bryant RA, Felmingham KL, Falconer EM, et al. Preliminary evidence of the short allele of the serotonin transporter gene predicting poor response to cognitive behavior therapy in posttraumatic stress disorder. Biological Psychiatry. 2010 ; 67: 1217-1219
8. Canli T, Lesch K-P. Long story short: The serotonin transporter in emotion regulation and social cognition. Nature Neuroscience. 2007 ; 10: 1103-1109
9. Caspi A, Sugden K, Moffitt T, et al. Influence of life stress on depression: Moderation by a polymorphism in the 5-HTT gene. Science. 2003 ; 301: 386-389
10. Celada P, Bortolozzi A, Artigas F. Serotonin 5-HT1A receptors as targets for agents to treat psychiatric disorders: Rationale and current status of research. CNS Drugs. 2013 ; 27: 703-716
11. Chen ES, Ernst C, Turecki G. The epigenetic effects of antidepressant treatment on human prefrontal cortex BDNF expression. International Journal of Neuropsychopharmacology. 2011 ; 14: 427-429
12. Cook RD, Weisberg S Residuals and Influence in Regression. New York: Chapman & Hall ; 1982 :
13. Crespi F. Apamin increases 5-HT cell firing in raphe dorsalis and extracellular 5-HT levels in amygdala: A concomitant in vivo study in anesthetized rats. Brain Research. 2009 ; 1281: 35-46
14. Dannlowski U, Ohrmann P, Bauer J, et al. Serotonergic genes modulate amygdala activity in major depression. Genes, Brain, and Behavior. 2007 ; 6: 672-676
15. Del-Ben CM, Deakin JFW, McKie S, et al. The effect of citalopram pretreatment on neuronal responses to neuropsychological tasks in normal volunteers: An FMRI study. Neuropsychopharmacology. 2005 ; 30: 1724-1734
16. Dinama O, Warren AM, Kulkarni J. The role of pharmacogenomic testing in psychiatry: Real world examples. Australian and New Zealand Journal of Psychiatry. 2014 ;:
17. Douglas KM, Porter RJ, Knight RG, Maruff P. Neuropsychological changes and treatment response in severe depression. The British Journal of Psychiatry. 2011 ; 198: 115-122
18. Freidlin B, Zheng G, Li Z, et al. Trend tests for case-control studies of genetic markers: Power, sample size and robustness. Human Heredity. 2002 ; 53: 146-152
19. Gatt JM, Nemeroff CB, Dobson-Stone C, et al. Interactions between BDNF Val66Met polymorphism and early life stress predict brain and arousal pathways to syndromal depression and anxiety. Molecular Psychiatry. 2009 ; 14: 681-695
20. Gibbons RD, Brown CH, Hur K, et al. Suicidal thoughts and behavior with antidepressant treatment: Reanalysis of the randomized placebo-controlled studies of fluoxetine and venlafaxine. Archives of General Psychiatry. 2012 ; 69: 580-587
21. Hariri AR, Holmes A. Genetics of emotional regulation: The role of the serotonin transporter in neural function. Trends in Cognitive Sciences. 2006 ; 10: 182-191
22. Hariri AR, Drabant EM, Munoz KE, et al. A susceptibility gene for affective disorders and the response of the human amygdala. Archives of General Psychiatry. 2005 ; 62: 146-152
23. Hariri AR, Drabant EM, Weinberger DR. Imaging genetics: Perspectives from studies of genetically driven variation in serotonin function and corticolimbic affective processing. Biological Psychiatry. 2006 ; 59: 888-897
24. Hariri AR, Mattay VS, Tessitore A, et al. Serotonin transporter genetic variation and the response of the human amygdala. Science. 2002 ; 297: 400-403
25. Harmer CJ. Emotional processing and antidepressant action. Current Topics in Behavioral Neurosciences. 2012 ; 14: 209-222
26. Harmer CJ, Goodwin GM, Cowen PJ. Why do antidepressants take so long to work? A cognitive neuropsychological model of antidepressant drug action. The British Journal of Psychiatry. 2009 ; 195: 102-108
27. Harsing LG. The pharmacology of the neurochemical transmission in the midbrain raphe nuclei of the rat. Current Neuropharmacology. 2006 ; 4: 313-339
28. Heils A, Teufel A, Petri S, et al. Allelic variation of human serotonin transporter gene expression. Journal of Neurochemistry. 1996 ; 66: 2621-2624
29. Heinz A, Smolka MN, Braus DF, et al. Serotonin transporter genotype (5-HTTLPR): Effects of neutral and undefined conditions on amygdala activation. Biological Psychiatry. 2007 ; 61: 1011-1014
30. Honey G, Bullmore E. Trends in pharmacological sciences: Human pharmacological MRI. Trends in Pharmacological Sciences. 2004 ; 25: 366-374
31. Hu X, Oroszi G, Chun J, et al. An expanded evaluation of the relationship of four alleles to the level of response to alcohol and the alcoholism risk. Alcoholism, Clinical and Experimental Research. 2005 ; 29: 8-16
32. Huezo-Diaz P, Uher R, Smith R, et al. Moderation of antidepressant response by the serotonin transporter gene. The British Journal of Psychiatry. 2009 ; 195: 30-38
33. Ichise M, Liow J-S, Lu J-Q, et al. Linearized reference tissue parametric imaging methods: Application to [11C]DASB positron emission tomography studies of the serotonin transporter in human brain. Journal of Cerebral Blood Flow and Metabolism. 2003 ; 23: 1096-1112
34. Kato M, Serretti A. Review and meta-analysis of antidepressant pharmacogenetic findings in major depressive disorder. Molecular Psychiatry. 2010 ; 15: 473-500
35. Kato M, Nonen S, Azuma J, et al. 5-HTTLPR rs25531A > G differentially influence paroxetine and fluvoxamine antidepressant efficacy. Journal of Clinical Psychopharmacology. 2013 ; 33: 131-132
36. Kemp AH, Gordon E, Rush AJ, et al. Improving the prediction of treatment response in depression: Integration of clinical, cognitive, psychophysiological, neuroimaging, and genetic measures. CNS Spectrums. 2008 ; 13: 1066-1086
37. Kemp AH, Gray MA, Silberstein RB, et al. Augmentation of serotonin enhances pleasant and suppresses unpleasant cortical electrophysiological responses to visual emotional stimuli in humans. NeuroImage. 2004a ; 22: 1084-1096
38. Kemp AH, Outhred T, Saunders S, et al. Impact of escitalopram on vagally mediated cardiovascular function in healthy participants: Implications for understanding differential age-related, treatment emergent effects. Psychopharmacology. 2013 ;:
39. Kemp AH, Silberstein RB, Armstrong SM, et al. Gender differences in the cortical electrophysiological processing of visual emotional stimuli. NeuroImage. 2004b ; 21: 632-646
40. Klein N, Sacher J, Geiss-Granadia T, et al. In vivo imaging of serotonin transporter occupancy by means of SPECT and [123I]ADAM in healthy subjects administered different doses of escitalopram or citalopram. Psychopharmacology. 2006 ; 188: 263-272
41. Kobiella A, Reimold M, Ulshöfer DE, et al. How the serotonin transporter 5-HTTLPR polymorphism influences amygdala function: The roles of in vivo serotonin transporter expression and amygdala structure. Translational Psychiatry. 2011 ; 1: e37
42. Kret ME, De Gelder B. A review on sex differences in processing emotional signals. Neuropsychologia. 2012 ; 50: 1211-1221
43. Kroenke K, Spitzer RL, Williams JBW. The PHQ-9. Validity of a brief depression severity measure. Journal of General Internal Medicine. 2001 ; 16: 606-613
44. Lang PJ, Bradley MM, Cuthbert BN International Affective Picture System (IAPS): Affective Ratings of Pictures and Instruction Manual. Gainesville, FL: University of Florida ; 2008 :
45. Lang PJ, Greenwald MK, Bradley MM, et al. Looking at pictures: Affective, facial, visceral, and behavioral reactions. Psychophysiology. 1993 ; 30: 261-273
46. Lanzenberger R, Kranz GS, Haeusler D, et al. Prediction of SSRI treatment response in major depression based on serotonin transporter interplay between median raphe nucleus and projection areas. NeuroImage. 2012 ; 63: 874-881
47. Lesch K-P, Gutknecht L. Pharmacogenetics of the serotonin transporter. Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2005 ; 29: 1062-1073
48. Lesch KP, Bengel D, Heils A, et al. Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science. 1996 ; 274: 1527-1531
49. Li D, He L. Meta-analysis supports association between serotonin transporter (5-HTT) and suicidal behavior. Molecular Psychiatry. 2007 ; 12: 47-54
50. Licht CMM, de Geus EJC, van Dyck R, et al. Longitudinal evidence for unfavorable effects of antidepressants on heart rate variability. Biological Psychiatry. 2010 ; 68: 861-868
51. Licinio J, Wong M-L. Pharmacogenomics of antidepressant treatment effects. Dialogues in Clinical Neuroscience. 2011 ; 13: 63-71
52. Luo Q, Holroyd T, Majestic C, et al. Emotional automaticity is a matter of timing. Journal of Neuroscience. 2010 ; 30: 5825-5829
53. Maldjian JA, Laurienti PJ, Kraft RA, et al. An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fMRI data sets. NeuroImage. 2003 ; 19: 1233-1239
54. Mann JJ, Huang YY, Underwood MD, et al. A serotonin transporter gene promoter polymorphism (5-HTTLPR) and prefrontal cortical binding in major depression and suicide. Archives of General Psychiatry. 2000 ; 57: 729-738
55. Meyer JH, Wilson AA, Sagrati S, et al. Serotonin transporter occupancy of five selective serotonin reuptake inhibitors at different doses: An [11C]DASB positron emission tomography study. The American Journal of Psychiatry. 2004 ; 161: 826-835
56. Munafò MR, Brown SM, Hariri AR. Serotonin transporter (5-HTTLPR) genotype and amygdala activation: A meta-analysis. Biological Psychiatry. 2008 ; 63: 852-857
57. Murphy SE, Norbury R, Godlewska BR, et al. The effect of the serotonin transporter polymorphism (5-HTTLPR) on amygdala function: A meta-analysis. Molecular Psychiatry. 2012 ; 18: 512-520
58. Murphy SE, Norbury R, O'Sullivan U, et al. Effect of a single dose of citalopram on amygdala response to emotional faces. The British Journal of Psychiatry. 2009 ; 194: 535-540
59. Outhred T, Das P, Dobson-Stone C, et al. The functional epistasis of 5-HTTLPR and BDNF Val66Met on emotion processing: A preliminary study. Brain and Behavior. 2012 ; 2: 778-788
60. Outhred T, Das P, Felmingham KL, et al. Impact of acute administration of escitalopram on the processing of emotional and neutral images: A randomized crossover fMRI study on healthy females. Journal of Psychiatry & Neuroscience. 2014 ; 39: 130118
61. Outhred T, Hawkshead BE, Wager TD, et al. Acute neural effects of selective serotonin reuptake inhibitors versus noradrenaline reuptake inhibitors on emotion processing: Implications for differential treatment efficacy. Neuroscience & Biobehavioral Reviews. 2013 ; 37: 1786-1800
62. Poldrack RA, Fletcher PC, Henson RN, et al. Guidelines for reporting an fMRI study. NeuroImage. 2008 ; 40: 409-414
63. Pourtois G, Spinelli L, Seeck M, et al. Temporal precedence of emotion over attention modulations in the lateral amygdala: Intracranial ERP evidence from a patient with temporal lobe epilepsy. Cognitive, Affective, & Behavioral Neuroscience. 2010 ; 10: 83-93
64. Pringle A, Browning M, Cowen PJ, et al. A cognitive neuropsychological model of antidepressant drug action. Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2011 ; 35: 1586-1592
65. Quinn CR, Dobson-Stone C, Outhred T, et al. The contribution of BDNF and 5-HTT polymorphisms and early life stress to the heterogeneity of major depressive disorder: A preliminary study. Australian and New Zealand Journal of Psychiatry. 2012 ; 46: 55-63
66. Reimold M, Smolka MN, Schumann G, et al. Midbrain serotonin transporter binding potential measured with [11C]DASB is affected by serotonin transporter genotype. Journal of Neural Transmission. 2007 ; 114: 635-639
67. Risch N, Herrell R, Lehner T, et al. Interaction between the serotonin transporter gene (5-HTTLPR), stressful life events, and risk of depression: A meta-analysis. Journal of the American Medical Association. 2009 ; 301: 2462-2471
68. Roiser JP, Elliott R, Sahakian BJ. Cognitive mechanisms of treatment in depression. Neuropsychopharmacology. 2012 ; 37: 117-136
69. Roseboom PH, Kalin NH The American Psychiatric Publishing Textbook of Psychopharmacology. 2011 ) Citalopram and S-citalopram. In: SchatzbergAFNemeroffCB (eds) The American Psychiatric Publishing Textbook of Psychopharmacology, 4th edition.Arlington, VA: American Psychiatric Publishing, Inc., pp.363-387. Schatzberg AF Nemeroff CB, ed. Arlington, VA: American Psychiatric Publishing, Inc., pp ; 2011: 363-387.
70. Ruhé HG, Ooteman W, Booij J, et al. Serotonin transporter gene promoter polymorphisms modify the association between paroxetine serotonin transporter occupancy and clinical response in major depressive disorder. Pharmacogenetics and Genomics. 2009 ; 19: 67-76
71. Serretti A, Kato M, De Ronchi D, et al. Meta-analysis of serotonin transporter gene promoter polymorphism (5-HTTLPR) association with selective serotonin reuptake inhibitor efficacy in depressed patients. Molecular Psychiatry. 2007 ; 12: 247-257
72. Smeraldi E, Zanardi R, Benedetti F, et al. Polymorphism within the promoter of the serotonin transporter gene and antidepressant efficacy of fluvoxamine. Molecular Psychiatry. 1998 ; 3: 508-511
73. Sogaard B, Mengel H, Rao N, et al. The pharmacokinetics of escitalopram after oral and intravenous administration of single and multiple doses to healthy subjects. Journal of Clinical Pharmacology. 2005 ; 45: 1400-1406
74. Spitzer RL, Kroenke K, Williams JBW, et al. A brief measure for assessing generalized anxiety disorder: The GAD-7. Archives of Internal Medicine. 2006 ; 166: 1092-1097
75. Stephenson CP, Karanges E, McGregor IS. Trends in the utilisation of psychotropic medications in Australia from 2000 to 2011. Australian and New Zealand Journal of Psychiatry. 2013 ; 47: 74-87
76. Tranter R, Bell D, Gutting P, et al. The effect of serotonergic and noradrenergic antidepressants on face emotion processing in depressed patients. Journal of Affective Disorders. 2009 ; 118: 87-93
77. Trivedi MH. Evaluation of outcomes with citalopram for depression using measurement-based care in STAR∗D: Implications for clinical practice. American Journal of Psychiatry. 2006 ; 163: 28-40
78. Tzourio-Mazoyer N, Landeau B, Papathanassiou D, et al. Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. NeuroImage. 2002 ; 15: 273-289
79. Zahajszky J, Rosenbaum JF, Tollefson GD The American Psychiatric Publishing Textbook of Psychopharmacology. 2011 ) Fluoxetine. In: SchatzbergAFNemeroffCB (eds) The American Psychiatric Publishing Textbook of Psychopharmacology, 4th edition.Arlington, VA: American Psychiatric Publishing, Inc., pp.289-306. Schatzberg AF Nemeroff CB, ed. Arlington, VA: American Psychiatric Publishing, Inc. ; 2011: 289-306.