Advertisement

Psychopharmacology

, Volume 231, Issue 14, pp 2759–2769 | Cite as

Serotoninergic effects on judgments and social learning of trustworthiness

  • Arndis Simonsen
  • Jørgen Scheel-Krüger
  • Mads Jensen
  • Andreas Roepstorff
  • Arne Møller
  • Chris D Frith
  • Daniel Campbell-Meiklejohn
Original Investigation

Abstract

Rationale

Certain disorders, such as depression and anxiety, to which serotonin dysfunction is historically associated, are also associated with lower assessments of other people's trustworthiness. Serotonergic changes are known to alter cognitive responses to threatening stimuli. This effect may manifest socially as reduced apparent trustworthiness of others. Trustworthiness judgments can emerge from either direct observation or references provided by third parties.

Objective

We assessed whether explicit judgments of trustworthiness and social influences on those judgments are altered by changes within serotonergic systems.

Methods

We implemented a double-blind between-subject design where 20 healthy female volunteers received a single dose of the selective serotonin reuptake inhibitor (SSRI) citalopram (2 × 20 mg), while 20 control subjects (matched on age, intelligence, and years of education) received a placebo. Subjects performed a face-rating task assessing how trustworthy they found 153 unfamiliar others (targets). After each rating, the subjects were told how other subjects, on average, rated the same target. The subjects then performed 30 min of distractor tasks before, unexpectedly, being asked to rate all 153 faces again, in a random order.

Results

Compared to subjects receiving a placebo, subjects receiving citalopram rated targets as less trustworthy. They also conformed more to opinions of others, when others rated targets to be even less trustworthy than subjects had initially indicated. The two effects were independent of negative effects of citalopram on subjective state.

Conclusions

This is evidence that serotonin systems can mediate explicit assessment and social learning of the trustworthiness of others.

Keywords

Serotonin SSRI Trustworthiness Social learning Threat processing Mood and anxiety disorders 

Notes

Acknowledgments

The project was funded by the Danish Research Foundation, The Lundbeck Foundation and a Sapere Aude young investigator award to DCM by the Danish Council for Independent Research. The experiment complies with the current laws of Denmark. Thanks to Prof. Trevor Robbins for comments on this manuscript. Thanks to Vasily Klucharev for providing the face images used in this task.

Conflict of interests

The authors declare no competing financial interest.

References

  1. Adell A, Celada P, Abellan MT, Artigas F (2002) Origin and functional role of the extracellular serotonin in the midbrain raphe nuclei. Brain Res Brain Res Rev 39:154–180PubMedCrossRefGoogle Scholar
  2. Adolphs R, Tranel D, Damasio AR (1998) The human amygdala in social judgment. Nature 393:470–474PubMedCrossRefGoogle Scholar
  3. Albert PR, Benkelfat C, Descarries L (2012) The neurobiology of depression—revisiting the serotonin hypothesis. I. Cellular and molecular mechanisms. Philos Trans R Soc Lond Ser B Biol Sci 367:2378–2381CrossRefGoogle Scholar
  4. Barefoot JC, Maynard KE, Beckham JC, Brummett BH, Hooker K, Siegler IC (1998) Trust, health, and longevity. J Behav Med 21:517–526PubMedCrossRefGoogle Scholar
  5. Beacher FD, Gray MA, Minati L, Whale R, Harrison NA, Critchley HD (2011) Acute tryptophan depletion attenuates conscious appraisal of social emotional signals in healthy female volunteers. Psychopharmacology (Berl) 213:603–613CrossRefGoogle Scholar
  6. Bech P, Tanghøj P, Andersen H, Overø K (2002) Citalopram dose-response revisited using an alternative psychometric approach to evaluate clinical effects of four fixed citalopram doses compared to placebo in patients with major depression. Psychopharmacology 163:20–25PubMedCrossRefGoogle Scholar
  7. Bienvenu OJ, Samuels JF, Costa PT, Reti IM, Eaton WW, Nestadt G (2004) Anxiety and depressive disorders and the five-factor model of personality: a higher- and lower-order personality trait investigation in a community sample. Depression Anxiety 20:92–97PubMedCrossRefGoogle Scholar
  8. Bigos KL, Pollock BG, Aizenstein HJ, Fisher PM, Bies RR, Hariri AR (2008) Acute 5-HT reuptake blockade potentiates human amygdala reactivity. Neuropsychopharmacology 33:3221–3225PubMedCentralPubMedCrossRefGoogle Scholar
  9. Browning M, Reid C, Cowen PJ, Goodwin GM, Harmer CJ (2007) A single dose of citalopram increases fear recognition in healthy subjects. J Psychopharmacol 21:684–690PubMedCrossRefGoogle Scholar
  10. Campbell-Meiklejohn DK, Simonsen A, Jensen M, Wohlert V, Gjerloff T, Scheel-Kruger J, Moller A, Frith CD, Roepstorff A (2012) Modulation of social influence by methylphenidate. Neuropsychopharmacology 37:1517–1525PubMedCentralPubMedCrossRefGoogle Scholar
  11. Cools R, Roberts AC, Robbins TW (2008a) Serotoninergic regulation of emotional and behavioural control processes. Trends Cogn Sci 12:31–40PubMedCrossRefGoogle Scholar
  12. Cools R, Robinson OJ, Sahakian B (2008b) Acute tryptophan depletion in healthy volunteers enhances punishment prediction but does not affect reward prediction. Neuropsychopharmacology 33:2291–2299PubMedCrossRefGoogle Scholar
  13. Cools R, Nakamura K, Daw ND (2011) Serotonin and dopamine: unifying affective, activational, and decision functions. Neuropsychopharmacology 36:98–113PubMedCentralPubMedCrossRefGoogle Scholar
  14. Cottrell CA, Neuberg SL, Li NP (2007) What do people desire in others? A sociofunctional perspective on the importance of different valued characteristics. J Pers Soc Psychol 92:208PubMedCrossRefGoogle Scholar
  15. Crisan LG, Pana S, Vulturar R, Heilman RM, Szekely R, Druga B, Dragos N, Miu AC (2009) Genetic contributions of the serotonin transporter to social learning of fear and economic decision making. Soc Cogn Affect Neurosci 4:399–408PubMedCentralPubMedCrossRefGoogle Scholar
  16. Crockett MJ, Clark L, Tabibnia G, Lieberman MD, Robbins TW (2008) Serotonin modulates behavioral reactions to unfairness. Science 320:1739PubMedCentralPubMedCrossRefGoogle Scholar
  17. Crockett MJ, Clark L, Robbins TW (2009) Reconciling the role of serotonin in behavioral inhibition and aversion: acute tryptophan depletion abolishes punishment-induced inhibition in humans. J Neurosci 29:11993–11999PubMedCentralPubMedCrossRefGoogle Scholar
  18. Crockett MJ, Clark L, Hauser MD, Robbins TW (2010) Serotonin selectively influences moral judgment and behavior through effects on harm aversion. Proc Natl Acad Sci 107:17433–17438PubMedCentralPubMedCrossRefGoogle Scholar
  19. Daw N, Kakade S, Dayan P (2002) Opponent interactions between serotonin and dopamine. Neural Netw 15:603–616PubMedCrossRefGoogle Scholar
  20. Dayan P, Huys QJ (2008) Serotonin, inhibition, and negative mood. PLoS Comput Biol 4:e4PubMedCentralPubMedCrossRefGoogle Scholar
  21. Dayan P, Huys QJ (2009) Serotonin in affective control. Annu Rev Neurosci 32:95–126PubMedCrossRefGoogle Scholar
  22. De Silva MJ, McKenzie K, Harpham T, Huttly SRA (2005) Social capital and mental illness: a systematic review. J Epidemiol Community Health 59:619PubMedCentralPubMedCrossRefGoogle Scholar
  23. Deakin JF, Graeff FG (1991) 5-HT and mechanisms of defence. J Psychopharmacol 5:305–315PubMedCrossRefGoogle Scholar
  24. Field AP (2009) Discovering statistics using SPSS. SAGE, LondonGoogle Scholar
  25. Garcia-Leal C, Del-Ben CM, Leal FM, Graeff FG, Guimaraes FS (2010) Escitalopram prolonged fear induced by simulated public speaking and released hypothalamic-pituitary-adrenal axis activation. J Psychopharmacol 24:683–694PubMedCrossRefGoogle Scholar
  26. Giovacchini G, Lang L, Ma Y, Herscovitch P, Eckelman WC, Carson RE (2005) Differential effects of paroxetine on raphe and cortical 5-HT1A binding: a PET study in monkeys. Neuroimage 28:238–248PubMedCrossRefGoogle Scholar
  27. Gorman JM (2006) Gender differences in depression and response to psychotropic medication. Gend Med 3:93–109PubMedCrossRefGoogle Scholar
  28. Grady CL, Siebner HR, Hornboll B, Macoveanu J, Paulson OB, Knudsen GM (2012) Acute pharmacologically induced shifts in serotonin availability abolish emotion-selective responses to negative face emotions in distinct brain networks. Eur Neuropsychopharmacol 23(5):368–378PubMedCrossRefGoogle Scholar
  29. Grillon C, Levenson J, Pine DS (2007) A single dose of the selective serotonin reuptake inhibitor citalopram exacerbates anxiety in humans: a fear-potentiated startle study. Neuropsychopharmacology 32:225–231PubMedCrossRefGoogle Scholar
  30. Harmer CJ, Bhagwagar Z, Perrett DI, Vollm BA, Cowen PJ, Goodwin GM (2003) Acute SSRI administration affects the processing of social cues in healthy volunteers. Neuropsychopharmacology 28:148–152PubMedCrossRefGoogle Scholar
  31. Harmer CJ, Shelley NC, Cowen PJ, Goodwin GM (2004) Increased positive versus negative affective perception and memory in healthy volunteers following selective serotonin and norepinephrine reuptake inhibition. Am J Psychiatr 161:1256–1263PubMedCrossRefGoogle Scholar
  32. Hedges DW, Brown BL, Shwalb DA, Godfrey K, Larcher AM (2007) The efficacy of selective serotonin reuptake inhibitors in adult social anxiety disorder: a meta-analysis of double-blind, placebo-controlled trials. J Psychopharmacol 21:102–111PubMedCrossRefGoogle Scholar
  33. Hood SD, Bell CJ, Nutt DJ (2005) Acute tryptophan depletion. Part I: rationale and methodology. Aust N Z J Psychiatry 39:558–564PubMedCrossRefGoogle Scholar
  34. Hovland CI, Weiss W (1951) The influence of source credibility on communication effectiveness. Publ Opin Q 15:635–650CrossRefGoogle Scholar
  35. Howell DC (2007) Statistical methods for psychology, 6th edn. Thomson Wadsworth, BelmontGoogle Scholar
  36. Jasinska AJ, Lowry CA, Burmeister M (2012) Serotonin transporter gene, stress and raphe-raphe interactions: a molecular mechanism of depression. Trends Neurosci 35:395–402PubMedCrossRefGoogle Scholar
  37. Joffe P, Larsen F, Pedersen V, Ring-Larsen H, Aaes-Jørgensen T, Sidhu J (1998) Single-dose pharmacokinetics of citalopram in patients with moderate renal insufficiency or hepatic cirrhosis compared with healthy subjects. Eur J Clin Pharmacol 54:237–242PubMedCrossRefGoogle Scholar
  38. Jørgensen H, Riis M, Knigge U, Kjaer A, Warberg J (2003) Serotonin receptors involved in vasopressin and oxytocin secretion. J Neuroendocrinol 15:242–249PubMedCrossRefGoogle Scholar
  39. Khan A, Brodhead AE, Schwartz KA, Kolts RL, Brown WA (2005) Sex differences in antidepressant response in recent antidepressant clinical trials. J Clin Psychopharmacol 25:318–324PubMedCrossRefGoogle Scholar
  40. Klucharev V, Hytonen K, Rijpkema M, Smidts A, Fernandez G (2009) Reinforcement learning signal predicts social conformity. Neuron 61:140–151PubMedCrossRefGoogle Scholar
  41. Klucharev V, Munneke MA, Smidts A, Fernandez G (2011) Downregulation of the posterior medial frontal cortex prevents social conformity. J Neurosci 31:11934–11940PubMedCrossRefGoogle Scholar
  42. Koscik TR, Tranel D (2010) The human amygdala is necessary for developing and expressing normal interpersonal trust. Neuropsychologia 49:602–611PubMedCentralPubMedCrossRefGoogle Scholar
  43. Langille DB, Asbridge M, Kisely S, Rasic D (2012) Suicidal behaviours in adolescents in Nova Scotia, Canada: protective associations with measures of social capital. Soc Psychiatry Psychiatr Epidemiol 47:1549–1555PubMedCrossRefGoogle Scholar
  44. Langlois JH, Kalakanis L, Rubenstein AJ, Larson A, Hallam M, Smoot M (2000) Maxims or myths of beauty? A meta-analytic and theoretical review. Psychol Bull 126:390PubMedCrossRefGoogle Scholar
  45. Lundbeck (2011) Association of CIPRAMIL (citalopram hydrobromide) with dose-dependent QT interval prolongation. Lundbeck Ltd, Milton KeynesGoogle Scholar
  46. Macoveanu J, Rowe JB, Hornboll B, Elliott R, Paulson OB, Knudsen GM, Siebner HR (2012) Playing it safe but losing anyway—serotonergic signaling of negative outcomes in dorsomedial prefrontal cortex in the context of risk-aversion. Eur Neuropsychopharmacol 23(8):919–930PubMedCrossRefGoogle Scholar
  47. McKie S, Del-Ben C, Elliott R, Williams S, del Vai N, Anderson I, Deakin JF (2005) Neuronal effects of acute citalopram detected by pharmacoMRI. Psychopharmacology 180:680–686PubMedCrossRefGoogle Scholar
  48. MHRA (2008) Public assessment report: citalopram 10 mg, citalopram 20 mg, citalopram 40 mg, citalopram hydrobromide PL 20532/0041-3 Aurobindo Pharma Ltd. MHRA, LondonGoogle Scholar
  49. Milak MS, Severance AJ, Prabhakaran J, Kumar JSD, Majo VJ, Ogden RT, Mann JJ, Parsey RV (2011) In vivo serotonin-sensitive binding of [11C]CUMI-101: a serotonin 1A receptor agonist positron emission tomography radiotracer. J Cereb Blood Flow Metab 31:243–249PubMedCentralPubMedCrossRefGoogle Scholar
  50. Mir S, Taylor D (1997) The adverse effects of antidepressants. Curr Opin Psychiatry 10:88–94CrossRefGoogle Scholar
  51. Montgomery S (1995) Selecting the optimum therapeutic dose of serotonin reuptake inhibitors: studies with citalopram. Int Clin Psychopharmacol 10:23–28PubMedCrossRefGoogle Scholar
  52. Murphy SE, Norbury R, O'Sullivan U, Cowen PJ, Harmer CJ (2009a) Effect of a single dose of citalopram on amygdala response to emotional faces. Br J Psychiatry 194:535–540PubMedCentralPubMedCrossRefGoogle Scholar
  53. Murphy SE, Yiend J, Lester KJ, Cowen PJ, Harmer CJ (2009b) Short-term serotonergic but not noradrenergic antidepressant administration reduces attentional vigilance to threat in healthy volunteers. Int J Neuropsychopharmacol 12:169–179PubMedCrossRefGoogle Scholar
  54. Noble S, Benfield P (1997) Citalopram. A review of its pharmacology, clinical efficacy and tolerability in the treatment of depression. CNS Drugs 8:410–431CrossRefGoogle Scholar
  55. Olfson M (2008) A case-control study of antidepressants and attempted suicide during early phase treatment of major depressive episodes. J Clin Psychiatry 69:425–432PubMedCrossRefGoogle Scholar
  56. Oosterhof NN, Todorov A (2008) The functional basis of face evaluation. Proc Natl Acad Sci U S A 105:11087–11092PubMedCentralPubMedCrossRefGoogle Scholar
  57. Papakostas GI, Charles D, Fava M (2010) Are typical starting doses of the selective serotonin reuptake inhibitors sub-optimal? A meta-analysis of randomized, double-blind, placebo-controlled, dose-finding studies in major depressive disorder. World J Biol Psychiatry 11:300–307PubMedCrossRefGoogle Scholar
  58. Passamonti L, Crockett MJ, Apergis-Schoute AM, Clark L, Rowe JB, Calder AJ, Robbins TW (2012) Effects of acute tryptophan depletion on prefrontal-amygdala connectivity while viewing facial signals of aggression. Biol Psychiatry 71:36–43PubMedCentralPubMedCrossRefGoogle Scholar
  59. Rogers RD (2011) The roles of dopamine and serotonin in decision making: evidence from pharmacological experiments in humans. Neuropsychopharmacology 36:114–132PubMedCentralPubMedCrossRefGoogle Scholar
  60. Rotenberg KJ, Macdonald KJ, King EV (2004) The relationship between loneliness and interpersonal trust during middle childhood. J Genet Psychol 165:233–249PubMedCrossRefGoogle Scholar
  61. Rotenberg KJ, Boulton MJ, Fox CL (2005) Cross-sectional and longitudinal relations among children's trust beliefs, psychological maladjustment and social relationships: are very high as well as very low trusting children at risk? J Abnorm Child Psychol 33:595–610PubMedCrossRefGoogle Scholar
  62. Rousseau DM, Sitkin SB, Burt RS, Camerer C (1998) Not so different after all: a cross-discipline view of trust. Acad Manag Rev 23:393–404CrossRefGoogle Scholar
  63. Selvaraj S, Turkheimer F, Rosso L, Faulkner P, Mouchlianitis E, Roiser JP, McGuire P, Cowen PJ, Howes O (2012) Measuring endogenous changes in serotonergic neurotransmission in humans: a [11C]CUMI-101 PET challenge study. Mol Psychiatry 17(12):1254–1260PubMedCrossRefGoogle Scholar
  64. Sommerfeld RD, Krambeck HJ, Semmann D, Milinski M (2007) Gossip as an alternative for direct observation in games of indirect reciprocity. Proc Natl Acad Sci 104:17435PubMedCentralPubMedCrossRefGoogle Scholar
  65. Soubrie P (1986) Serotonergic neurons and behavior. J Pharmacol 17:107–112PubMedGoogle Scholar
  66. Stallen M, De Dreu CK, Shalvi S, Smidts A, Sanfey AG (2012) The herding hormone: oxytocin stimulates in-group conformity. Psychol Sci 23:1288–1292PubMedCrossRefGoogle Scholar
  67. Sullivan MD, Ciechanowski PS, Russo JE, Soine LA, Jordan-Keith K, Ting HH, Caldwell JH (2009) Understanding why patients delay seeking care for acute coronary syndromes. Circ Cardiovasc Qual Outcomes 2:148–154PubMedCrossRefGoogle Scholar
  68. Theodoridou A, Rowe AC, Penton-Voak IS, Rogers PJ (2009) Oxytocin and social perception: oxytocin increases perceived facial trustworthiness and attractiveness. Horm Behav 56:128–132PubMedCrossRefGoogle Scholar
  69. Todorov A (2008) Evaluating faces on trustworthiness: an extension of systems for recognition of emotions signaling approach/avoidance behaviors. Ann N Y Acad Sci 1124:208–224PubMedCrossRefGoogle Scholar
  70. Todorov A, Mandisodza AN, Goren A, Hall CC (2005) Inferences of competence from faces predict election outcomes. Science 308:1623–1626PubMedCrossRefGoogle Scholar
  71. Tokuda Y, Jimba M, Yanai H, Fujii S, Inoguchi T (2008) Interpersonal trust and quality-of-life: a cross-sectional study in Japan. PLoS One 3:e3985PubMedCentralPubMedCrossRefGoogle Scholar
  72. Van Donkelaar E, Blokland A, Ferrington L, Kelly P, Steinbusch H, Prickaerts J (2011) Mechanism of acute tryptophan depletion: is it only serotonin? Mol Psychiatry 16:695–713PubMedCrossRefGoogle Scholar
  73. van Roekel E, Scholte RH, Verhagen M, Goossens L, Engels RC (2010) Loneliness in adolescence: gene × environment interactions involving the serotonin transporter gene. J Child Psychol Psychiatry Allied Discip 51:747–754CrossRefGoogle Scholar
  74. Van't Wout M, Sanfey A (2008) Friend or foe: the effect of implicit trustworthiness judgments in social decision-making. Cognition 108:796–803CrossRefGoogle Scholar
  75. Winston JS, Strange BA, O'Doherty J, Dolan RJ (2002) Automatic and intentional brain responses during evaluation of trustworthiness of faces. Nat Neurosci 5:277–283PubMedCrossRefGoogle Scholar
  76. Wood R, Rilling J, Sanfey A, Bhagwagar Z, Rogers R (2006) Effects of tryptophan depletion on the performance of an iterated Prisoner's Dilemma game in healthy adults. Neuropsychopharmacology 31:1075–1084PubMedCrossRefGoogle Scholar
  77. Young EA, Kornstein SG, Marcus SM, Harvey AT, Warden D, Wisniewski SR, Balasubramani G, Fava M, Trivedi MH, John Rush A (2009) Sex differences in response to citalopram: A STAR D report. J Psychiatr Res 43:503–511PubMedCentralPubMedCrossRefGoogle Scholar
  78. Zaki J, Schirmer J, Mitchell JP (2011) Social influence modulates the neural computation of value. Psychol Sci 22:894–900PubMedCrossRefGoogle Scholar
  79. Zimmer-Gembeck MJ, Pronk RE (2011) Relation of depression and anxiety to self- and peer-reported relational aggression. Aggress Behav 38:16–30PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Arndis Simonsen
    • 1
    • 2
  • Jørgen Scheel-Krüger
    • 1
  • Mads Jensen
    • 1
  • Andreas Roepstorff
    • 1
    • 2
  • Arne Møller
    • 1
  • Chris D Frith
    • 1
    • 2
    • 3
    • 4
  • Daniel Campbell-Meiklejohn
    • 1
    • 2
    • 5
  1. 1.Center of Functionally Integrative NeuroscienceAarhus UniversityAarhusDenmark
  2. 2.Interacting Minds CentreAarhus UniversityAarhusDenmark
  3. 3.Wellcome Centre for Functional NeuroimagingUniversity College LondonLondonUK
  4. 4.All Souls CollegeUniversity of OxfordOxfordUK
  5. 5.Department of PsychologyUniversity of CambridgeCambridgeUK

Personalised recommendations