Genetic influences on central and peripheral nervous system activity during fear conditioning

G Kastrati,X Chen,K B Jensen,M Fredrikson,R Kuja-Halkola,H Larsson,J Rosén,F Åhs

doi:10.1038/s41398-022-01861-w

Abstract

Fear conditioning is an evolutionarily conserved type of learning serving as a model for the acquisition of situationally induced anxiety. Brain function supporting fear conditioning may be genetically influenced, which in part could explain genetic susceptibility for anxiety following stress exposure. Using a classical twin design and functional magnetic resonance imaging, we evaluated genetic influences (h2) on brain activity and standard autonomic measures during fear conditioning. We found an additive genetic influence on mean brain activation (h2 = 0.34) and autonomic responses (h2 = 0.24) during fear learning. The experiment also allowed estimation of the genetic influence on brain activation during safety learning (h2 = 0.55). The mean safety, but not fear, related brain activation was genetically correlated with autonomic responses. We conclude that fear and safety learning processes, both involved in anxiety development, are moderately genetically influenced as expressed both in the brain and the body.

Highlights

Threat responses can be elicited by environmental cues through Pavlovian fear conditioning, whereby a neutral stimulus predicts the occurrence of an aversive event [1]
Fear conditioning can be studied experimentally in the laboratory by comparing autonomic responses to a fear cue paired with an aversive event with responses to a safety stimulus, that is never coupled with an aversive event [5]
Single nucleotide polymorphisms related to genes encoding receptors and enzymes expressed in brain have generally been examined [7–10]

Summary

INTRODUCTION

Threat responses can be elicited by environmental cues through Pavlovian fear conditioning, whereby a neutral stimulus predicts the occurrence of an aversive event [1]. Single nucleotide polymorphisms related to genes encoding receptors and enzymes expressed in brain have generally been examined [7–10] These studies may hold promise in revealing genetic pathways involved in conditioned fear, the sample sizes have so far been limited and results have been mixed. A recent example is fear conditioning studies on variants of the singlenucleotide polymorphism in the fatty acid amino hydrolase (FAAH) gene (rs324420), where one variant encodes an FAAH enzyme with reduced catabolic efficacy This single-nucleotide polymorphism has been found to predict extinction in some [11] but not all studies [12], or populations within studies [13]. There is correspondence across species in terms of neural circuitry supporting fear conditioning [18–20] This could indicate that findings of genetic influences on brain function in animal models could transfer to humans.

MATERIALS AND METHODS

Kastrati et al 3

RESULTS

Findings

CONFLICT OF INTEREST