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Three weeks of SSRI administration enhances the visual perceptual threshold - a randomized placebo-controlled study

  • Jon LansnerEmail author
  • Christian G. Jensen
  • Anders Petersen
  • Patrick M. Fisher
  • Vibe G. Frokjaer
  • Signe Vangkilde
  • Gitte M. Knudsen
Original Investigation

Abstract

Rationale

The serotonergic system has been repeatedly linked to visual attention in general, but the effects of selective serotonin reuptake inhibitor (SSRI) on specific components of visual attention remain unknown. Changes in distinct perceptual and cognitive processes are not readily evident in most attention paradigms.

Objective

In this study, we isolate basic components of visual attention to investigate potential effects of longer-term SSRI administration on non-emotional aspects of visual attention in healthy males.

Methods

In a randomized double-blind placebo-controlled design, 32 young healthy males were tested on multiple attentional parameters, before and after a 3-week SSRI intervention with fluoxetine (40 mg daily) or placebo. Data were modeled with a computational theory of visual attention to derive independent estimates of five distinct components of visual attention.

Results

The SSRI intervention selectively and significantly lowered the threshold for conscious visual perception. Specifically, we demonstrate that this improvement does not stem from a general increase in the speed of visual processing, as previously suggested, but specifically from a change in the perceptual threshold.

Conclusions

The study provides a novel description of the attentional dynamics affected by SSRI, while supporting previous findings on attentional effects of SSRI. Furthermore, it accentuates the utility of employing accuracy-based measures of attentional performance when conducting psychopharmacological research.

Keywords

SSRI Serotonin 5-HT Attention Perception Cognition Non-motor Unspeeded response Healthy Human TVA Theory of visual attention 

Notes

Funding information

The project was funded by a center grant from the Lundbeck Foundation to Center for Integrated Molecular Brain Imaging (Cimbi, www.cimbi.dk). JL is supported by a grant from the Lundbeck Foundation: Attention, impulsivity, and monoamines: from psychological functions to molecular mechanisms.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

References

  1. Aghajanian GK, Sanders-Bush E (2002) SerotoninGoogle Scholar
  2. Amado-Boccara I, Gougoulis N, Poirier Littre M, Galinowski A, Loo H (1995) Effects of antidepressants on cognitive functions: a review. Neurosci Biobehav Rev 19:479–493CrossRefGoogle Scholar
  3. Anderson IM, Del-Ben CM, Mckie S, Richardson P, Williams SR, Elliott R, Deakin JW (2007) Citalopram modulation of neuronal responses to aversive face emotions: a functional MRI study. Neuroreport 18:1351–1355CrossRefGoogle Scholar
  4. Bar-Haim Y, Lamy D, Pergamin L, Bakermans-Kranenburg MJ, Van Ijzendoorn MH (2007) Threat-related attentional bias in anxious and nonanxious individuals: a meta-analytic study. Psychol Bull 133:1–24CrossRefGoogle Scholar
  5. Bech P, Rasmussen N-A, Olsen LR, Noerholm V, Abildgaard W (2001) The sensitivity and specificity of the major depression inventory, using the present state examination as the index of diagnostic validity. J Affect Disord 66:159–164CrossRefGoogle Scholar
  6. Bigos KL, Pollock BG, Aizenstein HJ, Fisher PM, Bies RR, Hariri AR (2008) Acute 5-HT reuptake blockade potentiates human amygdala reactivity. Neuropsychopharmacology 33:3221–3225CrossRefGoogle Scholar
  7. Brunken WJ, Jin XT, Pis-Lopez AM (1993) The properties of the serotoninergic system in the retina. Prog Retin Res 12:75–99CrossRefGoogle Scholar
  8. Bundesen C (1990) A theory of visual attention. Psychol Rev 97:523–547CrossRefGoogle Scholar
  9. Bundesen C, Habekost T (2008) Principles of visual attention: linking mind and brain. Oxford University Press, OxfordCrossRefGoogle Scholar
  10. Campbell F, Gregory A (1960) Effect of size of pupil on visual acuityGoogle Scholar
  11. Carli M, Samanin R (1992) Serotonin2 receptor agonists and serotonergic anorectic drugs affect rats’ performance differently in a five-choice serial reaction time task. Psychopharmacology 106:228–234CrossRefGoogle Scholar
  12. Carli M, Samanin R (2000) The 5-HT1A receptor agonist 8-OH-DPAT reduces rats’ accuracy of attentional performance and enhances impulsive responding in a five-choice serial reaction time task: role of presynaptic 5-HT1A receptors. Psychopharmacology 149:259–268CrossRefGoogle Scholar
  13. Charlier C, Pinto E, Ansseau M, Plomteux G (2000) Relationship between clinical effects, serum drug concentration, and concurrent drug interactions in depressed patients treated with citalopram, fluoxetine, clomipramine, paroxetine or venlafaxine. Hum Psychopharmacol Clin Exp 15:453–459CrossRefGoogle Scholar
  14. Del-Ben CM, Deakin JW, Mckie S, Delvai NA, Williams SR, Elliott R, Dolan M, Anderson IM (2005) The effect of citalopram pretreatment on neuronal responses to neuropsychological tasks in normal volunteers: an FMRI study. Neuropsychopharmacology 30:1724–1734CrossRefGoogle Scholar
  15. Derogatis LR (1975) Symptom checklist-90-revised (SCL-90-R). Minneapolis, MN: NCS Assessments.Google Scholar
  16. Desimone R, Duncan J (1995) Neural mechanisms of selective visual attention. Annu Rev Neurosci 18:193–222CrossRefGoogle Scholar
  17. Dumont GJ, De Visser SJ, Cohen AF, Van Gerven JM, Biomarker Working Group of the German Association for Applied Human Pharmacology (2005) Biomarkers for the effects of selective serotonin reuptake inhibitors (SSRIs) in healthy subjects. Br J Clin Pharmacol 59:495–510CrossRefGoogle Scholar
  18. Duncan J, Bundesen C, Olson A, Humphreys G, Chavda S, Shibuya H (1999) Systematic analysis of deficits in visual attention. J Exp Psychol Gen 128:450–478CrossRefGoogle Scholar
  19. Dyrholm M, Kyllingsbæk S, Espeseth T, Bundesen C (2011) Generalizing parametric models by introducing trial-by-trial parameter variability: the case of TVA. J Math Psychol 55:416–429CrossRefGoogle Scholar
  20. Eysel UT, Burandt U (1984) Fluorescent tube light evokes flicker responses in visual neurons. Vis Res 24:943–948CrossRefGoogle Scholar
  21. Fairweather D, Pozzo C, Kerr J, Lafferty S, Hindmarch I (1997) Citalopram compared to dothiepin and placebo: effects on cognitive function and psychomotor performance. Hum Psychopharmacol Clin Exp 12:119–126CrossRefGoogle Scholar
  22. Finke K, Dodds CM, Bublak P, Regenthal R, Baumann F, Manly T, Müller U (2010) Effects of modafinil and methylphenidate on visual attention capacity: a TVA-based study. Psychopharmacology 210:317–329CrossRefGoogle Scholar
  23. Fisher PM, Haahr ME, Jensen CG, Frokjaer VG, Siebner HR, Knudsen GM (2015) Fluctuations in [11C] SB207145 PET binding associated with change in threat-related amygdala reactivity in humans. Neuropsychopharmacology 40:1510–1518CrossRefGoogle Scholar
  24. Forsell Y (2005) The major depression inventory versus schedules for clinical assessment in neuropsychiatry in a population sample. Soc Psychiatry Psychiatr Epidemiol 40:209–213CrossRefGoogle Scholar
  25. Frisén L (1980) The neurology of visual acuity. Brain J Neurol 103:639–670CrossRefGoogle Scholar
  26. Gerdelat-Mas A, Loubinoux I, Tombari D, Rascol O, Chollet F, Simonetta-Moreau M (2005) Chronic administration of selective serotonin reuptake inhibitor (SSRI) paroxetine modulates human motor cortex excitability in healthy subjects. NeuroImage 27:314–322CrossRefGoogle Scholar
  27. Geyer MA (1995) Serotonergic functions in arousal and motor activity. Behav Brain Res 73:31–35CrossRefGoogle Scholar
  28. Gur M, Snodderly DM (1997) A dissociation between brain activity and perception: chromatically opponent cortical neurons signal chromatic flicker that is not perceived. Vis Res 37:377–382CrossRefGoogle Scholar
  29. Haahr M, Fisher P, Jensen C, Frokjaer V, Mc Mahon B, Madsen K, Baaré W, Lehel S, Norremolle A, Rabiner E (2014) Central 5-HT4 receptor binding as biomarker of serotonergic tonus in humans: a [11C]SB207145 PET study. Mol Psychiatry 19:427–432CrossRefGoogle Scholar
  30. Harmer CJ, Mackay CE, Reid CB, Cowen PJ, Goodwin GM (2006) Antidepressant drug treatment modifies the neural processing of nonconscious threat cues. Biol Psychiatry 59:816–820CrossRefGoogle Scholar
  31. Hart WM, Adler FH (1992) Adler’s physiology of the eye: clinical application. Mosby IncGoogle Scholar
  32. Hindmarch I (1987) Three antidepressants (amitriptyline, dothiepin, fluoxetine), with and without alcohol, compared with placebo on tests of psychomotor ability related to car driving. Hum Psychopharmacol Clin Exp 2:177–183CrossRefGoogle Scholar
  33. Hindmarch I (1995) The behavioural toxicity of the selective serotonin reuptake inhibitors. Int Clin Psychopharmacol 9:13–18CrossRefGoogle Scholar
  34. Hindmarch I, Bhatti J (1988) Psychopharmacological effects of sertraline in normal, healthy volunteers. Europ J Clin Pharmacol 35:221–223CrossRefGoogle Scholar
  35. Hindmarch I, Harrison C (1988) The effects of paroxetine and other antidepressants in combination with alcohol in psychomotor activity related to car driving. Hum Psychopharmacol Clin Exp 3:13–20CrossRefGoogle Scholar
  36. Jannuzzi G, Gatti G, Magni P, Spina E, Pacifici R, Zuccaro P, Torta R, Guarneri L, Perucca E (2002) Plasma concentrations of the enantiomers of fluoxetine and norfluoxetine: sources of variability and preliminary observations on relations with clinical response. Ther Drug Monit 24:616–627CrossRefGoogle Scholar
  37. Jensen CG, Vangkilde S, Frokjaer V, Hasselbalch SG (2012) Mindfulness training affects attention—or is it attentional effort? J Exp Psychol Gen 141:106–123CrossRefGoogle Scholar
  38. Jensen CG, Lansner J, Petersen A, Vangkilde SA, Ringkøbing SP, Frokjaer VG, Adamsen D, Knudsen GM, Denninger JW, Hasselbalch SG (2015) Open and calm—a randomized controlled trial evaluating a public stress reduction program in Denmark. BMC Public Health 15:1CrossRefGoogle Scholar
  39. Kerr J, Fairweather D, Mahendran R, Hindmarch I (1992) The effects of paroxetine, alone and in combination with alcohol on psychomotor performance and cognitive function in the elderly. Int Clin PsychopharmacolGoogle Scholar
  40. Knorr U, Kessing LV (2010) The effect of selective serotonin reuptake inhibitors in healthy subjects. A systematic review. Nord J Psychiatry 64:153–163CrossRefGoogle Scholar
  41. Laroche RB, Morgan RE (2007) Adolescent fluoxetine exposure produces enduring, sex-specific alterations of visual discrimination and attention in rats. Neurotoxicol Teratol 29:96–107CrossRefGoogle Scholar
  42. Lingjaerde O, Ahlfors U, Bech P, Dencker S, Elgen K (1987) The UKU side effect rating scale: a new comprehensive rating scale for psychotropic drugs and a cross-sectional study of side effects in neuroleptic-treated patients. Acta Psychiatr Scand 76:1–100CrossRefGoogle Scholar
  43. Loubinoux I, Pariente J, Boulanouar K, Carel C, Manelfe C, Rascol O, Celsis P, Chollet F (2002) A single dose of the serotonin neurotransmission agonist paroxetine enhances motor output: double-blind, placebo-controlled, fMRI study in healthy subjects. NeuroImage 15:26–36CrossRefGoogle Scholar
  44. Loubinoux I, Tombari D, Pariente J, Gerdelat-Mas A, Franceries X, Cassol E, Rascol O, Pastor J, Chollet F (2005) Modulation of behavior and cortical motor activity in healthy subjects by a chronic administration of a serotonin enhancer. NeuroImage 27:299–313CrossRefGoogle Scholar
  45. Macoveanu J, Fisher PM, Haahr ME, Frokjaer VG, Knudsen GM, Siebner HR (2014) Effects of selective serotonin reuptake inhibition on neural activity related to risky decisions and monetary rewards in healthy males. NeuroImage 99:434–442CrossRefGoogle Scholar
  46. Mariño J, Schummers J, Lyon DC, Schwabe L, Beck O, Wiesing P, Obermayer K, Sur M (2005) Invariant computations in local cortical networks with balanced excitation and inhibition. Nat Neurosci 8:194–201CrossRefGoogle Scholar
  47. Mccormick D, Wang Z (1991) Serotonin and noradrenaline excite GABAergic neurones of the guinea-pig and cat nucleus reticularis thalami. J Physiol 442:235–255CrossRefGoogle Scholar
  48. Monckton JE, Mccormick DA (2002) Neuromodulatory role of serotonin in the ferret thalamus. J Neurophysiol 87:2124–2136CrossRefGoogle Scholar
  49. Moreau AW, Amar M, Callebert J, Fossier P (2013) Serotonergic modulation of LTP at excitatory and inhibitory synapses in the developing rat visual cortex. Neuroscience 238:148–158CrossRefGoogle Scholar
  50. Nardella A, Rocchi L, Conte A, Bologna M, Suppa A, Berardelli A (2014) Inferior parietal lobule encodes visual temporal resolution processes contributing to the critical flicker frequency threshold in humansGoogle Scholar
  51. Nathan P, Sitaram G, Stough C, Silberstein R, Sali A (2000) Serotonin, noradrenaline and cognitive function: a preliminary investigation of the acute pharmacodynamic effects of a serotonin versus a serotonin and noradrenaline reuptake inhibitor. Behav Pharmacol 11:639–642CrossRefGoogle Scholar
  52. Nord M, Finnema SJ, Halldin C, Farde L (2013) Effect of a single dose of escitalopram on serotonin concentration in the non-human and human primate brain. Int J Neuropsychopharmacol 1–10Google Scholar
  53. Pape H-C, Mccormick DA (1989) Noradrenaline and serotonin selectively modulate thalamic burst firing by enhancing a hyperpolarization-activated cation current. Nature 340:715–718CrossRefGoogle Scholar
  54. Parrott A (1982) Critical flicker fusion thresholds and their relationship to other measures of alertness. Pharmacopsychiatry 15:39–43CrossRefGoogle Scholar
  55. Schmitt JA, Riedel WJ, Vuurman EF, Kruizinga M, Ramaekers JG (2002) Modulation of the critical flicker fusion effects of serotonin reuptake inhibitors by concomitant pupillary changes. Psychopharmacology 160:381–386CrossRefGoogle Scholar
  56. Shibuya H, Bundesen C (1988) Visual selection from multielement displays: measuring and modeling effects of exposure duration. J Exp Psychol Hum Percept Perform 14:591–600CrossRefGoogle Scholar
  57. Steriade M, Llinás RR (1988) The functional states of the thalamus and the associated neuronal interplay. Physiol Rev 68:649–742CrossRefGoogle Scholar
  58. Vangkilde S, Bundesen C, Coull JT (2011) Prompt but inefficient: nicotine differentially modulates discrete components of attention. Psychopharmacology 218:667–680CrossRefGoogle Scholar
  59. Wells EF, Bernstein GM, Scott BW, Bennett PJ, Mendelson JR (2001) Critical flicker frequency responses in visual cortex. Exp Brain Res 139:106–110CrossRefGoogle Scholar
  60. Who, W.H.O (1993) The ICD-10 classification of mental and behavioural disorders: diagnostic criteria for researchGoogle Scholar
  61. Winstanley CA, Chudasama Y, Dalley JW, Theobald DE, Glennon JC, Robbins TW (2003) Intra-prefrontal 8-OH-DPAT and M100907 improve visuospatial attention and decrease impulsivity on the five-choice serial reaction time task in rats. Psychopharmacology 167:304–314CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of PsychologyUniversity of CopenhagenCopenhagenDenmark
  2. 2.Neurobiology Research UnitRigshospitaletCopenhagenDenmark
  3. 3.Child and Adolescent Mental Health Centre, Mental Health ServicesCapital RegionDenmark
  4. 4.Faculty of Medicine and HealthUniversity of CopenhagenCopenhagenDenmark

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