Polymorphisms that affect GABA neurotransmission predict processing of aversive prediction errors in humans

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dc.contributor.authorBaetu, I.
dc.contributor.authorPitcher, J.
dc.contributor.authorCohen-Woods, S.
dc.contributor.authorLancer, B.
dc.contributor.authorBeu, N.
dc.contributor.authorForeman, L.
dc.contributor.authorTaylor, P.
dc.contributor.authorBurns, N.
dc.date.issued2018
dc.description.abstractLearning is one of our most adaptive abilities, allowing us to adjust our expectations about future events. Aberrant learning processes may underlie disorders such as anxiety, motivating the search for the neural mechanisms that underpin learning. Animal studies have shown that the neurotransmitter GABA is required for the computation of prediction errors, the mismatches between anticipated and experienced outcomes, which drive new learning. Given that evidence from human studies is lacking, we sought to determine whether these findings extend to humans. Here, in two samples of Caucasian individuals, we investigated whether genetically determined individual differences in GABA neurotransmission predict the P3 event-related potential, an EEG component known to reflect prediction error processing. Consistent with the results of animal studies, we show that a weighted genetic risk score computed from the number of GABRB2 rs1816072 A alleles (associated with increased expression of the GABAA receptor β2 subunit gene) and the number of ErbB4 rs7598440 T alleles (associated with increased GABA concentration) predicts optimal prediction error processing during aversive classical conditioning with both visual (Experiment 1, N = 90; p = .010) and auditory (Experiment 2; N = 92; p = .031) unconditioned stimuli. Our finding that optimal processing of aversive prediction errors is reduced in individuals genetically predisposed towards decreased GABA neurotransmission suggests a potential mechanism linking GABA and anxiety. Specifically, reduced GABA signalling via GABAA receptors could result in aberrant learning from aversive experiences and vulnerability to anxiety disorders.
dc.description.statementofresponsibilityIrina Baetu, Julia B. Pitcher, Sarah Cohen-Woods, Benjamin Lancer, Nathan Beu, Lauren M. Foreman, Paul D. Taylor, Nicholas R. Burns
dc.identifier.citationNeuroImage, 2018; 176:176-192
dc.identifier.doi10.1016/j.neuroimage.2018.04.058
dc.identifier.issn1053-8119
dc.identifier.issn1095-9572
dc.identifier.orcidBaetu, I. [0000-0002-5565-7136]
dc.identifier.orcidPitcher, J. [0000-0002-9648-7540]
dc.identifier.orcidCohen-Woods, S. [0000-0003-2199-6129]
dc.identifier.orcidLancer, B. [0000-0002-9339-7355]
dc.identifier.orcidBeu, N. [0000-0002-9797-3663]
dc.identifier.orcidForeman, L. [0000-0003-3441-604X]
dc.identifier.orcidBurns, N. [0000-0003-3456-6734]
dc.identifier.urihttp://hdl.handle.net/2440/114220
dc.language.isoen
dc.publisherElsevier
dc.relation.granthttp://purl.org/au-research/grants/arc/DE140100750
dc.rights© 2018 Elsevier Inc. All rights reserved.
dc.source.urihttps://doi.org/10.1016/j.neuroimage.2018.04.058
dc.subjectPrediction error; classical conditioning; electroencephalography; GABA; polymorphism
dc.titlePolymorphisms that affect GABA neurotransmission predict processing of aversive prediction errors in humans
dc.typeJournal article
pubs.publication-statusPublished

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