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dc.contributor.authorZmigrod, Leor
dc.contributor.authorRobbins, Trevor W
dc.date.accessioned2021-10-22T23:30:30Z
dc.date.available2021-10-22T23:30:30Z
dc.date.issued2021-12-06
dc.identifier.issn0898-929X
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/329797
dc.description.abstractCognitive flexibility has been hypothesized to be neurochemically rooted in dopamine neurotransmission. Nonetheless, underpowered sample sizes and contradictory meta-analytic findings have obscured the role of dopamine genes in cognitive flexibility and neglected potential gene-gene interactions. In this largest neurocognitive-genetic study to date (n = 1400), single nucleotide polymorphisms associated with elevated prefrontal dopamine levels (catechol-O-methyltransferase; rs4680) and diminished striatal dopamine (C957T; rs6277) were both implicated in Wisconsin Card Sorting Test performance. Crucially, however, these genetic effects were only evident in low-IQ participants, suggesting high intelligence compensates for, and eliminates, the effect of dispositional dopamine functioning on flexibility. This interaction between cognitive systems may explain and resolve previous empirical inconsistencies in highly educated participant samples. Moreover, compensatory gene-gene interactions were discovered between catechol-O-methyltransferase and DRD2, such that genotypes conferring either elevated prefrontal dopamine or diminished striatal dopamine-via heightened striatally concentrated D2 dopamine receptor availability-are sufficient for cognitive flexibility, but neither is necessary. The study has therefore revealed a form of epistatic redundancy or substitutability among dopamine systems in shaping adaptable thought and action, thus defining boundary conditions for dopaminergic effects on flexible behavior. These results inform theories of clinical disorders and psychopharmacological interventions and uncover complex fronto-striatal synergies in human flexible cognition.
dc.description.sponsorshipGates Cambridge Trust
dc.publisherMIT Press - Journals
dc.rightsAll rights reserved
dc.rights.urihttp://www.rioxx.net/licenses/all-rights-reserved
dc.titleDopamine, Cognitive Flexibility, and IQ: Epistatic Catechol-O-MethylTransferase:DRD2 Gene-Gene Interactions Modulate Mental Rigidity.
dc.typeArticle
prism.publicationNameJ Cogn Neurosci
dc.identifier.doi10.17863/CAM.77242
rioxxterms.versionofrecord10.1162/jocn_a_01784
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
dc.contributor.orcidZmigrod, Leor [0000-0001-8270-7955]
dc.contributor.orcidRobbins, Trevor W [0000-0003-0642-5977]
dc.identifier.eissn1530-8898
rioxxterms.typeJournal Article/Review
cam.issuedOnline2021-12-01
cam.orpheus.successTue Feb 01 19:02:05 GMT 2022 - Embargo updated
cam.orpheus.counter5
rioxxterms.freetoread.startdate2021-12-06


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