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Serotoninergic effects on judgments and social learning of trustworthiness

Psychopharmacology volume 231, pages 2759–2769 (2014)Cite this article

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.

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References

  • 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 39:154–180

    CAS  PubMed  Article  Google Scholar 

  • Adolphs R, Tranel D, Damasio AR (1998) The human amygdala in social judgment. Nature 393:470–474

    CAS  PubMed  Article  Google Scholar 

  • 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 367:2378–2381

    CAS  Article  Google Scholar 

  • Barefoot JC, Maynard KE, Beckham JC, Brummett BH, Hooker K, Siegler IC (1998) Trust, health, and longevity. J Behav Med 21:517–526

    CAS  PubMed  Article  Google Scholar 

  • 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) 213:603–613

    CAS  Article  Google Scholar 

  • 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 163:20–25

    CAS  PubMed  Article  Google Scholar 

  • 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 20:92–97

    PubMed  Article  Google Scholar 

  • Bigos KL, Pollock BG, Aizenstein HJ, Fisher PM, Bies RR, Hariri AR (2008) Acute 5-HT reuptake blockade potentiates human amygdala reactivity. Neuropsychopharmacology 33:3221–3225

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  • Browning M, Reid C, Cowen PJ, Goodwin GM, Harmer CJ (2007) A single dose of citalopram increases fear recognition in healthy subjects. J Psychopharmacol 21:684–690

    CAS  PubMed  Article  Google Scholar 

  • 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 37:1517–1525

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  • Cools R, Roberts AC, Robbins TW (2008a) Serotoninergic regulation of emotional and behavioural control processes. Trends Cogn Sci 12:31–40

    PubMed  Article  Google Scholar 

  • Cools R, Robinson OJ, Sahakian B (2008b) Acute tryptophan depletion in healthy volunteers enhances punishment prediction but does not affect reward prediction. Neuropsychopharmacology 33:2291–2299

    CAS  PubMed  Article  Google Scholar 

  • Cools R, Nakamura K, Daw ND (2011) Serotonin and dopamine: unifying affective, activational, and decision functions. Neuropsychopharmacology 36:98–113

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  • 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 92:208

    PubMed  Article  Google Scholar 

  • 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 4:399–408

    PubMed Central  PubMed  Article  Google Scholar 

  • Crockett MJ, Clark L, Tabibnia G, Lieberman MD, Robbins TW (2008) Serotonin modulates behavioral reactions to unfairness. Science 320:1739

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  • 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 29:11993–11999

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  • 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 107:17433–17438

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  • Daw N, Kakade S, Dayan P (2002) Opponent interactions between serotonin and dopamine. Neural Netw 15:603–616

    PubMed  Article  Google Scholar 

  • Dayan P, Huys QJ (2008) Serotonin, inhibition, and negative mood. PLoS Comput Biol 4:e4

    PubMed Central  PubMed  Article  Google Scholar 

  • Dayan P, Huys QJ (2009) Serotonin in affective control. Annu Rev Neurosci 32:95–126

    CAS  PubMed  Article  Google Scholar 

  • De Silva MJ, McKenzie K, Harpham T, Huttly SRA (2005) Social capital and mental illness: a systematic review. J Epidemiol Community Health 59:619

    PubMed Central  PubMed  Article  Google Scholar 

  • Deakin JF, Graeff FG (1991) 5-HT and mechanisms of defence. J Psychopharmacol 5:305–315

    CAS  PubMed  Article  Google Scholar 

  • Field AP (2009) Discovering statistics using SPSS. SAGE, London

    Google Scholar 

  • Forest Laboratories (2009) Celexa. http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020822s037,021046s015lbl.pdf. Accessed May 2009.

  • 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 24:683–694

    CAS  PubMed  Article  Google Scholar 

  • 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 28:238–248

    PubMed  Article  Google Scholar 

  • Gorman JM (2006) Gender differences in depression and response to psychotropic medication. Gend Med 3:93–109

    PubMed  Article  Google Scholar 

  • 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):368–378

    PubMed  Article  Google Scholar 

  • 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 32:225–231

    CAS  PubMed  Article  Google Scholar 

  • 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 28:148–152

    CAS  PubMed  Article  Google Scholar 

  • 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 161:1256–1263

    PubMed  Article  Google Scholar 

  • 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 21:102–111

    CAS  PubMed  Article  Google Scholar 

  • Hood SD, Bell CJ, Nutt DJ (2005) Acute tryptophan depletion. Part I: rationale and methodology. Aust N Z J Psychiatry 39:558–564

    PubMed  Article  Google Scholar 

  • Hovland CI, Weiss W (1951) The influence of source credibility on communication effectiveness. Publ Opin Q 15:635–650

    Article  Google Scholar 

  • Howell DC (2007) Statistical methods for psychology, 6th edn. Thomson Wadsworth, Belmont

    Google Scholar 

  • Jasinska AJ, Lowry CA, Burmeister M (2012) Serotonin transporter gene, stress and raphe-raphe interactions: a molecular mechanism of depression. Trends Neurosci 35:395–402

    CAS  PubMed  Article  Google Scholar 

  • 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 54:237–242

    CAS  PubMed  Article  Google Scholar 

  • Jørgensen H, Riis M, Knigge U, Kjaer A, Warberg J (2003) Serotonin receptors involved in vasopressin and oxytocin secretion. J Neuroendocrinol 15:242–249

    PubMed  Article  Google Scholar 

  • Khan A, Brodhead AE, Schwartz KA, Kolts RL, Brown WA (2005) Sex differences in antidepressant response in recent antidepressant clinical trials. J Clin Psychopharmacol 25:318–324

    PubMed  Article  Google Scholar 

  • Klucharev V, Hytonen K, Rijpkema M, Smidts A, Fernandez G (2009) Reinforcement learning signal predicts social conformity. Neuron 61:140–151

    CAS  PubMed  Article  Google Scholar 

  • Klucharev V, Munneke MA, Smidts A, Fernandez G (2011) Downregulation of the posterior medial frontal cortex prevents social conformity. J Neurosci 31:11934–11940

    CAS  PubMed  Article  Google Scholar 

  • Koscik TR, Tranel D (2010) The human amygdala is necessary for developing and expressing normal interpersonal trust. Neuropsychologia 49:602–611

    PubMed Central  PubMed  Article  Google Scholar 

  • 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 47:1549–1555

    PubMed  Article  Google Scholar 

  • 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 126:390

    CAS  PubMed  Article  Google Scholar 

  • Lundbeck (2011) Association of CIPRAMIL (citalopram hydrobromide) with dose-dependent QT interval prolongation. Lundbeck Ltd, Milton Keynes

  • 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):919–930

    PubMed  Article  Google Scholar 

  • 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 180:680–686

    CAS  PubMed  Article  Google Scholar 

  • MHRA (2008) Public assessment report: citalopram 10 mg, citalopram 20 mg, citalopram 40 mg, citalopram hydrobromide PL 20532/0041-3 Aurobindo Pharma Ltd. MHRA, London

  • 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 31:243–249

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  • Mir S, Taylor D (1997) The adverse effects of antidepressants. Curr Opin Psychiatry 10:88–94

    Article  Google Scholar 

  • Montgomery S (1995) Selecting the optimum therapeutic dose of serotonin reuptake inhibitors: studies with citalopram. Int Clin Psychopharmacol 10:23–28

    PubMed  Article  Google Scholar 

  • 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 194:535–540

    PubMed Central  PubMed  Article  Google Scholar 

  • 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 12:169–179

    CAS  PubMed  Article  Google Scholar 

  • Noble S, Benfield P (1997) Citalopram. A review of its pharmacology, clinical efficacy and tolerability in the treatment of depression. CNS Drugs 8:410–431

    CAS  Article  Google Scholar 

  • Olfson M (2008) A case-control study of antidepressants and attempted suicide during early phase treatment of major depressive episodes. J Clin Psychiatry 69:425–432

    PubMed  Article  Google Scholar 

  • Oosterhof NN, Todorov A (2008) The functional basis of face evaluation. Proc Natl Acad Sci U S A 105:11087–11092

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  • 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 11:300–307

    PubMed  Article  Google Scholar 

  • 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 71:36–43

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  • Rogers RD (2011) The roles of dopamine and serotonin in decision making: evidence from pharmacological experiments in humans. Neuropsychopharmacology 36:114–132

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  • Rotenberg KJ, Macdonald KJ, King EV (2004) The relationship between loneliness and interpersonal trust during middle childhood. J Genet Psychol 165:233–249

    PubMed  Article  Google Scholar 

  • 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 33:595–610

    PubMed  Article  Google Scholar 

  • Rousseau DM, Sitkin SB, Burt RS, Camerer C (1998) Not so different after all: a cross-discipline view of trust. Acad Manag Rev 23:393–404

    Article  Google Scholar 

  • 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):1254–1260

    CAS  PubMed  Article  Google Scholar 

  • 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 104:17435

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  • Soubrie P (1986) Serotonergic neurons and behavior. J Pharmacol 17:107–112

    CAS  PubMed  Google Scholar 

  • Stallen M, De Dreu CK, Shalvi S, Smidts A, Sanfey AG (2012) The herding hormone: oxytocin stimulates in-group conformity. Psychol Sci 23:1288–1292

    PubMed  Article  Google Scholar 

  • 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 2:148–154

    PubMed  Article  Google Scholar 

  • Theodoridou A, Rowe AC, Penton-Voak IS, Rogers PJ (2009) Oxytocin and social perception: oxytocin increases perceived facial trustworthiness and attractiveness. Horm Behav 56:128–132

    CAS  PubMed  Article  Google Scholar 

  • Todorov A (2008) Evaluating faces on trustworthiness: an extension of systems for recognition of emotions signaling approach/avoidance behaviors. Ann N Y Acad Sci 1124:208–224

    PubMed  Article  Google Scholar 

  • Todorov A, Mandisodza AN, Goren A, Hall CC (2005) Inferences of competence from faces predict election outcomes. Science 308:1623–1626

    CAS  PubMed  Article  Google Scholar 

  • 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:e3985

    PubMed Central  PubMed  Article  Google Scholar 

  • 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 16:695–713

    PubMed  Article  Google Scholar 

  • 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 51:747–754

    Article  Google Scholar 

  • Van't Wout M, Sanfey A (2008) Friend or foe: the effect of implicit trustworthiness judgments in social decision-making. Cognition 108:796–803

    Article  Google Scholar 

  • Winston JS, Strange BA, O'Doherty J, Dolan RJ (2002) Automatic and intentional brain responses during evaluation of trustworthiness of faces. Nat Neurosci 5:277–283

    CAS  PubMed  Article  Google Scholar 

  • 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 31:1075–1084

    CAS  PubMed  Article  Google Scholar 

  • 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 43:503–511

    PubMed Central  PubMed  Article  Google Scholar 

  • Zaki J, Schirmer J, Mitchell JP (2011) Social influence modulates the neural computation of value. Psychol Sci 22:894–900

    PubMed  Article  Google Scholar 

  • Zimmer-Gembeck MJ, Pronk RE (2011) Relation of depression and anxiety to self- and peer-reported relational aggression. Aggress Behav 38:16–30

    PubMed  Article  Google Scholar 

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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.

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Authors and Affiliations

  1. Center of Functionally Integrative Neuroscience, Aarhus University, 8000, Aarhus, Denmark

    Arndis Simonsen, Jørgen Scheel-Krüger, Mads Jensen, Andreas Roepstorff, Arne Møller, Chris D Frith & Daniel Campbell-Meiklejohn

  2. Interacting Minds Centre, Aarhus University, 8000, Aarhus, Denmark

    Arndis Simonsen, Andreas Roepstorff, Chris D Frith & Daniel Campbell-Meiklejohn

  3. Wellcome Centre for Functional Neuroimaging, University College London, WC1N 3BG, London, UK

    Chris D Frith

  4. All Souls College, University of Oxford, OX1 4AL, Oxford, UK

    Chris D Frith

  5. Department of Psychology, University of Cambridge, Downing Street, CB2 3EB, Cambridge, UK

    Daniel Campbell-Meiklejohn

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  1. Arndis Simonsen
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  2. Jørgen Scheel-Krüger
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  3. Mads Jensen
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  5. Arne Møller
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  7. Daniel Campbell-Meiklejohn
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Correspondence to Daniel Campbell-Meiklejohn.

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Simonsen, A., Scheel-Krüger, J., Jensen, M. et al. Serotoninergic effects on judgments and social learning of trustworthiness. Psychopharmacology 231, 2759–2769 (2014). https://doi.org/10.1007/s00213-014-3444-2

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  • DOI: https://doi.org/10.1007/s00213-014-3444-2

Keywords

  • Serotonin
  • SSRI
  • Trustworthiness
  • Social learning
  • Threat processing
  • Mood and anxiety disorders