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dc.contributor.authorKanen, Jonathan W
dc.contributor.authorApergis-Schoute, Annemieke M
dc.contributor.authorYellowlees, Robyn
dc.contributor.authorArntz, Fréderique E
dc.contributor.authorvan der Flier, Febe E
dc.contributor.authorPrice, Annabel
dc.contributor.authorCardinal, Rudolf N
dc.contributor.authorChristmas, David M
dc.contributor.authorClark, Luke
dc.contributor.authorSahakian, Barbara J
dc.contributor.authorCrockett, Molly J
dc.contributor.authorRobbins, Trevor W
dc.date.accessioned2022-02-24T16:05:15Z
dc.date.available2022-02-24T16:05:15Z
dc.date.issued2021-12
dc.date.submitted2020-04-22
dc.identifier.issn1359-4184
dc.identifier.others41380-021-01240-9
dc.identifier.other1240
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/334415
dc.descriptionFunder: Gates Cambridge Trust; doi: https://doi.org/10.13039/501100005370
dc.descriptionFunder: DH | National Institute for Health Research (NIHR); doi: https://doi.org/10.13039/501100000272
dc.description.abstractSerotonin is involved in updating responses to changing environmental circumstances. Optimising behaviour to maximise reward and minimise punishment may require shifting strategies upon encountering new situations. Likewise, autonomic responses to threats are critical for survival yet must be modified as danger shifts from one source to another. Whilst numerous psychiatric disorders are characterised by behavioural and autonomic inflexibility, few studies have examined the contribution of serotonin in humans. We modelled both processes, respectively, in two independent experiments (N = 97). Experiment 1 assessed instrumental (stimulus-response-outcome) reversal learning whereby individuals learned through trial and error which action was most optimal for obtaining reward or avoiding punishment initially, and the contingencies subsequently reversed serially. Experiment 2 examined Pavlovian (stimulus-outcome) reversal learning assessed by the skin conductance response: one innately threatening stimulus predicted receipt of an uncomfortable electric shock and another did not; these contingencies swapped in a reversal phase. Upon depleting the serotonin precursor tryptophan-in a double-blind randomised placebo-controlled design-healthy volunteers showed impairments in updating both actions and autonomic responses to reflect changing contingencies. Reversal deficits in each domain, furthermore, were correlated with the extent of tryptophan depletion. Initial Pavlovian conditioning, moreover, which involved innately threatening stimuli, was potentiated by depletion. These results translate findings in experimental animals to humans and have implications for the neurochemical basis of cognitive inflexibility.
dc.description.sponsorshipNIHR
dc.languageen
dc.publisherSpringer Science and Business Media LLC
dc.subjectArticle
dc.subject/631/477
dc.subject/631/378
dc.subjectarticle
dc.titleSerotonin depletion impairs both Pavlovian and instrumental reversal learning in healthy humans.
dc.typeArticle
dc.date.updated2022-02-24T16:05:14Z
prism.endingPage7210
prism.issueIdentifier12
prism.publicationNameMol Psychiatry
prism.startingPage7200
prism.volume26
dc.identifier.doi10.17863/CAM.81830
dcterms.dateAccepted2021-07-09
rioxxterms.versionofrecord10.1038/s41380-021-01240-9
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidKanen, Jonathan W [0000-0002-4095-5405]
dc.contributor.orcidCardinal, Rudolf N [0000-0002-8751-5167]
dc.contributor.orcidChristmas, David M [0000-0001-5423-0221]
dc.contributor.orcidClark, Luke [0000-0003-1103-2422]
dc.contributor.orcidSahakian, Barbara J [0000-0001-7352-1745]
dc.contributor.orcidRobbins, Trevor W [0000-0003-0642-5977]
dc.identifier.eissn1476-5578
pubs.funder-project-idMedical Research Council (MC_PC_17213)
pubs.funder-project-idWellcome Trust (104631/Z/14/Z)
cam.issuedOnline2021-08-24


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