title: Peripheral Serotonin 1B Receptor Transcription Predicts the Effect of Acute Tryptophan Depletion on Risky Decision-Making.
abstract: The effects of acute tryptophan depletion on human decision-making suggest that serotonin modulates the processing of rewards and punishments. However, few studies have assessed which of the many types of serotonin receptors are responsible.
  
  
  
  Using a within-subject, double-blind, sham-controlled design in 26 subjects, we examined whether individual differences in serotonin system gene transcription, measured in peripheral blood, predicted the effect of acute tryptophan depletion on decision-making. Participants performed a task in which they chose between successive pairs of fixed, lower-stakes (control) and variable, higher-stakes (experimental) gambles, each involving wins or losses. In 21 participants, mRNA from 9 serotonin system genes was measured in whole blood prior to acute tryptophan depletion: 5-HT1B, 5-HT1F, 5-HT2A, 5-HT2B, 5-HT3A, 5-HT3E, 5-HT7 (serotonin receptors), 5-HTT (the serotonin transporter), and tryptophan hydroxylase 1.
  
  
  
  Acute tryptophan depletion did not significantly influence participants' sensitivity to probability, wins, or losses, although there was a trend for a lower tendency to choose experimental gambles overall following depletion. Significant positive correlations, which survived correction for multiple comparisons, were detected between baseline 5-HT1B mRNA levels and acute tryptophan depletion-induced increases in both the overall tendency to choose the experimental gamble and sensitivity to wins. No significant relationship was observed with any other peripheral serotonin system markers. Computational analyses of decision-making data provided results consistent with these findings.
  
  
  
  These results suggest that the 5-HT1B receptor may modulate the effects of acute tryptophan depletion on risky decision-making. Peripheral levels of serotonin markers may predict response to treatments that act upon the serotonin system, such as selective serotonin reuptake inhibitors.
authors.affiliation: Institute of Cognitive Neuroscience, University College London, London, United Kingdom; Psychiatry and Biobehavioral Sciences, Semel Institute, University of California, Los Angeles, California.
authors.forename: Paul
authors.initials: P
authors.lastname: Faulkner
authors.affiliation: Institute of Cognitive Neuroscience, University College London, London, United Kingdom; Psychiatry and Biobehavioral Sciences, Semel Institute, University of California, Los Angeles, California.
authors.forename: Federico
authors.initials: F
authors.lastname: Mancinelli
authors.affiliation: Institute of Cognitive Neuroscience, University College London, London, United Kingdom; Psychiatry and Biobehavioral Sciences, Semel Institute, University of California, Los Angeles, California.
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Lockwood
authors.affiliation: Institute of Cognitive Neuroscience, University College London, London, United Kingdom; Psychiatry and Biobehavioral Sciences, Semel Institute, University of California, Los Angeles, California.
authors.forename: Mar
authors.initials: M
authors.lastname: Matarin
authors.affiliation: Institute of Cognitive Neuroscience, University College London, London, United Kingdom; Psychiatry and Biobehavioral Sciences, Semel Institute, University of California, Los Angeles, California.
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Dolan
authors.affiliation: Institute of Cognitive Neuroscience, University College London, London, United Kingdom; Psychiatry and Biobehavioral Sciences, Semel Institute, University of California, Los Angeles, California.
authors.forename: Nick W
authors.initials: NW
authors.lastname: Wood
authors.affiliation: Institute of Cognitive Neuroscience, University College London, London, United Kingdom; Psychiatry and Biobehavioral Sciences, Semel Institute, University of California, Los Angeles, California.
authors.forename: Peter
authors.initials: P
authors.lastname: Dayan
authors.affiliation: Gatsby Computational Neuroscience Unit, and CoMPLEX Centre for Mathematics, Physics and Engineering in the Life Sciences and Experimental Biology, University College London, London, United Kingdom; Experimental Psychology, University of Oxford, Oxford, United Kingdom; Clinical and Experimental Epilepsy, Institute of Neurology, and Wellcome Trust Centre for Neuroimaging, University College London, London, United Kingdom; Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, United Kingdom.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Roiser
mesh_terms: D000328:Adult; D001007:Anxiety / Q000097:blood; D003657:Decision Making / Q000502:physiology*; D004311:Double-Blind Method; D005260:Female; D005715:Gambling / Q000097:blood*; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D012333:RNA, Messenger / Q000097:blood; D011930:Reaction Time / Q000502:physiology; D044302:Receptor, Serotonin, 5-HT1B / Q000097:blood*; D012727:Sex Characteristics; D014364:Tryptophan / Q000097:blood / Q000172:deficiency*
chemical_list: D012333:RNA, Messenger; D044302:Receptor, Serotonin, 5-HT1B; D014364:Tryptophan
keywords: 5-HT1B; acute tryptophan depletion; decision-making; risk; serotonin