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

Irina Baetu, Julia Pitcher, Sarah Cohen-Woods, Bernjamin Lancer, Nathan Beu, Lauren Foreman, Paul Taylor, Nicholas Burns

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Learning 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.

Original languageEnglish
Pages (from-to)179-192
Number of pages14
JournalNeuroimage
Volume176
DOIs
Publication statusPublished - 1 Aug 2018

Keywords

  • Classical conditioning
  • Electroencephalography
  • GABA
  • Polymorphism
  • Prediction error

Fingerprint

Dive into the research topics of 'Polymorphisms that affect GABA neurotransmission predict processing of aversive prediction errors in humans'. Together they form a unique fingerprint.

Cite this